Dermatology

To the Editor: We report a case of desmoplastic small round cell tumour (DSRCT) in the liver of a 23-year-old woman who presented with a recurrent non-pruritic rash. The woman had a generalised macular rash, predominantly on the back and upper thighs. She reported recurrent similar skin rashes over the previous 4 months that had been treated with intermittent courses of oral antibiotics. She had felt mild fatigue during the 3 weeks prior to presentation. She was otherwise well, but had non-tender hepatomegaly (17 cm) on examination. There was no peripheral lymphadenopathy. Levels of cholestatic liver enzymes were mildly raised (γ-glutamyl transpeptidase, 198 IU/L; alkaline phosphatase, 246 IU/L), but bilirubin and immunoglobulin levels were normal. The serum level of cancer antigen 125 (CA125) was 141 U/mL (reference range, < 35 U/mL). A computed tomography scan of the chest and abdomen showed multiple hepatic lesions (Box 1). A radiologically guided biopsy was taken, and histological examination revealed the typical morphology and immunophenotype of DSRCT (Box 2). Our patient was counselled regarding diagnosis and likely poor prognosis. We did not attempt to preserve fertility, because we felt treatment should not be delayed and that life expectancy was limited. Chemotherapy with alternating VAC (vincristine, doxorubicin and cyclophosphamide) and IE (ifosfamide and etoposide) cycles was started promptly. Molecular testing for EWS1/WT1 (see below) was not performed, as there was insufficient biopsy tissue available. The patient’s rashes disappeared after one treatment cycle, and we postulate that the rashes were paraneoplastic and immune-mediated. Restaging scans after four cycles of chemotherapy demonstrated a partial response. Stem cells were pre-emptively mobilised to store for possible subsequent autologous transplantation. The patient will be reassessed after eight cycles. If there is a significant response, the options of high-dose chemotherapy with autologous stem cell transplantation and/or debulking surgery will be explored. To our knowledge, this is the first Australian report of DSRCT in a woman presenting with recurrent rash. DSRCT is a rare, aggressive tumour that predominantly affects males in early adulthood.1 There is a single Australian report of a 15-year-old boy who died of DSRCT 20 months after diagnosis.2 The histogenesis of DSRCT is unknown, but it exhibits divergent differentiation, expressing epithelial, muscular and neural proteins. It is characterised by the chromosomal translocation t(11;22)(pl3;ql2), formed by fusion of the Ewing sarcoma gene (EWS1) to the Wilms tumour suppressor gene (WT1).3 Patients typically present with non-specific symptoms, and the tumours are usually intra-abdominal. The level of CA125 is often raised, but this does not assist with diagnosis or monitoring.1 Diagnosis is by histology and immunohistochemistry, complemented by cytogenetic identification of an EWS1/WT1 translocation. Patients with DSRCT have a poor prognosis, with a median survival of 15 months. Given the rarity of the tumour, there are no data from randomised phase III trials to guide management. Aggressive multimodality treatment offers the highest chance of disease control and prolonged overall survival.1,4 Palliative debulking can be of benefit if curative resection is not feasible. Radiotherapy is best employed as consolidation treatment after chemotherapy and surgery.1,5 Combination chemotherapy is the backbone of therapy and offers improved progression-free survival. The P6 protocol,6 which uses alternating cycles of VAC and IE with 21 days between cycles, is most widely employed. Subsequent high-dose myeloablative chemotherapy with autologous stem cell support may be beneficial.4 1 Pre-treatment computed tomography scan of the patient’s abdomen, showing multiple hypodense lesions in the enlarged liver 2 Histological sections from a core biopsy of a desmoplastic small round cell tumour (DSRCT) in the liver A: Irregular nests of small round hyperchromatic tumour cells were embedded in a prominent fibrotic stroma (haematoxylin–eosin stain, original magnification ×250). A diagnosis of DSRCT was confirmed by immunohistochemical stains (B–D). B: The muscle marker desmin. C: An epithelial marker AE1/3. D: The Wilms tumour marker WT1. (Original magnification of images B–D ×100.)

Meena Okera · David Moffat · Sudarshan Selva-Nayagam

Two sisters aged 6 and 11 years presented with pruritic inflammatory lesions, one on the arm and one on the shoulder (Figure). The lesions appeared 72 hours after the girls had black henna tattoos applied while they were on holiday in Egypt. On examination, each girl had eczematous eruptions that perfectly outlined the tattoo. Patch tests were positive for paraphenylenediamine, a known potent contact allergen. Black henna tattoos are a frequent source of sensitisation to paraphenylenediamine among Australian tourists to South-East Asia.1 Potential significant consequences include allergic reactions to hair dyes, textile dyes, anaesthetics, sulfonamides and sunscreens containing p-aminobenzoic acid.

Pablo J Almeida · Leopoldo Borrego

Currently available, relatively safe vaccines may help tackle this serious and increasing public health problem Melanoma is a serious public health problem in many countries throughout the world, with an incidence increasing at a faster rate than that of any other cancer except lung cancer among women.1 In Europe and the United States, the incidence increased threefold between 1970 and 2000, although improved awareness meant that the mortality rate did not rise so steeply. The risk of melanoma varies greatly (around 100-fold) from region to region, with the highest risk being in Australia where, in 2003, the annual risk was 46.9 per 100 000 population, with estimated lifetime risks of one in 28 and one in 19 up to the ages of 75 and 85 years, respectively.2 With the exclusion of non-melanotic skin cancers, melanoma was the fourth most prevalent cancer in Australia, accounting for 10% of all cases, and the age-standardised risk of melanoma increased by 14% between 1993 and 2003. There are anecdotal reports of regression and even complete resolution of melanoma in patients who had developed serious febrile infections.3 Although these cases are rare and perhaps coincidental, they encouraged us to conduct epidemiological studies on the impact of prior infectious diseases and vaccinations on the risk of melanoma. We therefore established the Febrile Infections and Melanoma (FEBIM) working group in six European countries and Israel, within the Epidemiological Section of the Melanoma Cooperative Group of the European Organization for Research and Treatment of Cancer (EORTC). In an evaluation of our EORTC case–control study, the FEBIM group established that a history of severe but increasingly uncommon infections, with fever above 38.5°C, including sepsis, pneumonia, pulmonary tuberculosis and Staphylococcus aureus infection, was associated with a reduced risk of melanoma.4 Moreover, in patients with histories of severe infections, the extent of risk reduction was directly related to the number of infections. Thus those with histories of one, two to three, and four or more infections had odds ratios of 0.66, 0.63 and 0.32, respectively, and this trend was statistically significant (P = 0.004). It was also established that vaccination early in life against smallpox (with vaccinia vaccine) or tuberculosis (with BCG vaccine), or both, conferred a significant and enduring degree of protection against melanoma. Adjusted odds ratios were 0.40 (95% CI, 0.18–0.85) for BCG alone, 0.60 (95% CI, 0.36–0.99) for vaccinia alone and 0.41 (95% CI, 0.25–0.67) for both vaccines. Not only did these vaccinations afford protection against melanoma, it was subsequently established in an EORTC cohort study of patients with melanoma, that those who developed melanoma had a significantly better prognosis if they had received one or both vaccinations, or had previously had serious but uncommon infections.5 Although confirmatory studies in different settings are required, the multicentre nature of our studies, the high degree of internal consistency of the observations, and the close parallels between their retrospective and prospective arms enhance confidence in the findings. A clue as to how certain vaccinations and infections might protect against melanoma came from the finding that a patient recruited for a trial of a melanoma vaccine had an expanded population of CD8+ T cells that recognised an epitope coded for by a human endogenous retrovirus of the HERV-K family.6 These viruses entered the human germ line millions of years ago and, although no longer capable of replication, can still code for gene products. A possible role of their gene products in the development of melanoma has been the subject of recent research.7 The HERV-K-MEL peptide is expressed on the surface of most human melanomas,6 and it was therefore postulated that a major component of the observed protection by certain infections and vaccinations is the generation of populations of CD8+ T cells cross-reacting with this epitope.8 Accordingly, amino acid sequences with homologies to HERV-K-MEL were sought among pathogens and vaccines, and were found in those associated with protection, but not in those that did not confer protection. A structurally similar sequence was also found in the 17D yellow fever vaccine, suggesting that it might likewise confer protection, and this prediction was confirmed in a recent pilot study of 28 000 adults vaccinated with this vaccine; this pilot study also showed that there was a period of around 10 years between vaccination and observed protection, indicating that the induced immune response is most effective at the time of tumour initiation, which may precede clinical manifestation by several years.9 This protection seems, therefore, to result from prevention of tumour initiation rather than the killing of melanoma cells already present in the body. So, it is important to emphasise that, in contrast to their likely preventive properties, BCG and vaccinia vaccines are of little or no value in treating established melanomas.4,7 Treatment of melanoma by immune modulation is much more complex than prevention, although several approaches of greatly varying complexity hold out hope for effective immunotherapeutic strategies in the future.10 However, our FEBIM studies indicate that certain currently available and relatively well tolerated vaccines against infectious diseases are able to make a significant impact on the serious and increasing public health problem of melanoma. Although it is unlikely that smallpox vaccination will be re-introduced for this purpose, the increasing global incidence of tuberculosis, including extreme drug-resistant forms, makes an additional case for considering widespread neonatal BCG vaccination. Yellow fever vaccine is another possibility as it is cheap and safe, although its efficacy in preventing melanoma requires confirmation in more extensive studies. The currently available evidence indicates the need for further studies to determine whether modifications of vaccination programs to include strategies to reduce the risk of melanoma would be of benefit, especially in high-risk countries such as Australia.

John M Grange MSc, MD · Bernd Krone MD PhD · Klaus F Kölmel MD · Giuseppe Mastrangelo MD

There is still no cure, but what advances have been made in managing this disabling condition? In its more aggravated forms diffuse scleroderma is one of the most terrible of all human ills. Like Tithonus [a Greek mythological hero who was granted immortality but not eternal youth] to “wither slowly” and like him to be “beaten down and marred and wasted” until one is literally a mummy, encased in an evershrinking, slowly contracting skin of steel, is a fate not pictured in any tragedy, ancient or modern. Sir William Osler, 18981 Scleroderma encompasses the name of a disease and a clinical sign (thickened skin) that have eluded any unifying mechanism of causation. While we still await a cure, new and significant pharmacological agents are now available that can assist in the symptomatic treatment and disease modification of this condition. The disease is uncommon, with Australian estimates of prevalence per 10 000 population ranging from 0.4–0.9 (Sydney, 1974–1988)2 to 1.47 (South Australia, 1993)3 to 2.4 (Tasmania, 2007).4 Scleroderma is classified into either localised (skin alone) disease or systemic (internal organ involvement ± skin) disease, which is known as systemic sclerosis. The principal subsets of systemic sclerosis are: diffuse cutaneous systemic sclerosis, limited cutaneous systemic sclerosis, systemic sclerosis sine scleroderma (systemic disease with no skin involvement), environmentally induced scleroderma, overlap syndromes and pre-scleroderma. In limited disease, skin thickening is limited to the extremities distal to the elbows and knees, and the face. Diffuse disease, at its maximal extent, affects not only the skin of the distal extremities and face but also the skin over the proximal extremities and trunk. The disease has three pathological features: fibrosis with excessive collagen and other ground substance deposition; vasculopathy involving small and large vessels; and smooth muscle atrophy. In diffuse systemic sclerosis, inflammation and fibrosis predominate, whereas in limited disease, vascular changes predominate. While skin involvement (dermal inflammation and fibrosis) is associated with variable morbidity, it is the systemic manifestations, especially pulmonary and cardiac, and occasionally renal and gastrointestinal, that are responsible for much of the disease-related premature mortality. Therapy is classified as either “disease-modifying” or “symptomatic” and is tailored to the individual’s tolerance and need. Therapeutic decisions are determined by the pattern of organ involvement (vital or non-vital), underlying pathological features, and other comorbidities. General measures such as staying warm, using gloves and skin moisturisers, taking antireflux or bowel motility agents, modifying timing and volume of meals, brushing teeth regularly to prevent caries, using eye drops for sicca symptoms, and avoiding aggravating factors are important first steps in treating and managing the condition. In the early onset of systemic sclerosis, an activated immune system (Box 1) may be important in the pathogenesis of subsequent fibrotic and vascular lesions, so early disease-modifying drug therapy is aimed at suppressing the immune response. Immunosuppressive drugs such as methotrexate, cyclophosphamide and mycophenolate, often in conjunction with judicious use of corticosteroids (there is some controversy surrounding the causal association between high-dose corticosteroids and scleroderma renal crisis), intravenous gammaglobulin, and minocycline, have been used with varying measures of success. The levels of evidence for therapeutic intervention strategies are outlined in Box 2. “Heavier” immunosuppression, with or without haemopoietic stem cell rescue, is contemplated in patients with early inflammatory vital organ involvement of the lung or myocardium.6,7 Two large multicentre Phase III studies — the ASTIS (Autologous Stem cell Transplantation International Scleroderma) Trial in Europe, and the SCOT (Scleroderma: Cyclophosphamide Or Transplantation) study in the United States — to determine the relative efficacy of haemopoietic stem cell transplantation compared with less rigorous immunosuppression are well underway. In Australia, we have performed autologous stem cell transplantation in seven patients with systemic sclerosis who had progressive vital organ involvement and in whom conventional immunosuppression had failed, and noted a dramatic, sustained, long-term remission in four of them that featured marked skin softening, stabilisation of interstitial lung disease and a three- to fourfold fall in antinuclear antibody titre (H J E, personal communication). These findings support the use of autologous stem cell transplantation as a disease-modifying modality. The use of mesenchymal stem cells (MSCs) in the treatment of arthritic disease is novel, and this approach has shown great potential because of the ease of isolation, rapid growth and extensive culture expansion of MSCs suitable for therapeutic use. In diseases such as scleroderma where there is excessive mesenchymal overactivity, MSCs are an ideal candidate cell type for tissue regeneration and repair of damaged structures. Trials of therapeutic uses of MSCs are currently in progress.8 Therapies directed toward modification of established fibrosis have been uniformly disappointing. D-penicillamine, previously the gold standard of scleroderma therapy, has fallen into disrepute after a US multicentre study showed no outcome difference between very low dose and usual dose D-penicillamine therapy.9 However, occasionally patients will exhibit resolution of skin fibrosis with little or no therapeutic intervention. Pulmonary arterial hypertension is a relatively common complication of systemic sclerosis and is caused by pulmonary arterial narrowing and thickening leading to increased pulmonary vascular resistance and arterial pressures (> 25 mmHg). As early diagnosis and treatment can have a profound effect on outcome, it is extremely important to screen patients for this condition. The gold-standard screening procedure is right heart catheterisation. There is level I evidence5 of efficacy of three categories of medications for pulmonary arterial hypertension: endothelin receptor antagonists, prostanoids, and phosphodiesterase inhibitors. These may be used as a single agent or in combination, with combined epoprostenol and sildenafil being more efficacious than combined bosentan and sildenafil. The use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers has been found to favourably modify the outcome of the vascular pathological features of scleroderma renal crisis. Symptomatic therapies for microvascular hyperreactivity, upper and lower gastrointestinal dysmotility, and musculoskeletal symptoms are outlined in Box 2. Promising new approaches include the use of a protein tyrosine kinase inhibitor, imatinib mesylate (Glivec, Novartis), that interferes with the signalling of platelet-derived growth factor and transforming growth factor-β, two pivotal mediators of the fibrotic process of systemic sclerosis. However, no biological agent has shown definitive evidence of efficacy thus far. Overall, despite the obvious absence of a cure, progress is being made in the understanding and management of this chronic and disabling rheumatic condition. 1 Pathophysiology of systemic sclerosis, with possible sites for therapeutic intervention Rational therapy would be designed to (1) prevent endothelial cell damage; (2) alter communication between mononuclear cells; (3) prevent mononuclear cell stimulation of fibroblasts; (4) prevent mast cell degranulation; (5) block fibroblast production or extrusion of procollagen; or (6) increase solubilisation of preformed collagen. Diagram courtesy of Professor Thomas Medsger, University of Pittsburgh. 2 Therapeutic intervention strategies for systemic sclerosis, with levels of evidence* Organ-specific features† Therapy (level of evidence) Cardiovascular (> 95%) (i) Microvascular (> 95%) Raynaud’s syndrome (> 95%) Efficacious: calcium channel blockers (II); topical glyceryl trinitrate (I); prazosin (I); intravenous iloprost (I); losartan (I); endothelin receptor antagonists; phosphodiesterase-5 inhibitors Disappointing: cisaprost; oral iloprost Promising: autologous progenitor cell implantation (II); protein tyrosine kinase ± Rho‑kinase inhibitors Digital ulcers Efficacious: as above; statins (I); bosentan (I); sildenafil (I) (ii) Macrovascular Myocardium (5%) Efficacious: immunosuppressives (III) Pericardium Efficacious: corticosteroids ± immunosuppressives Skin/adnexae (> 95%) Sclerosis Efficacious: cyclosporin (?II); tacrolimus (?II); cyclophosphamide (III) Disappointing: methotrexate (I) Promising: intravenous gammaglobulin (III) Respiratory (40%) Interstitial lung disease‡ Efficacious: cyclophosphamide (II) Promising: azathioprine (remission) (I) Pulmonary arterial hypertension Efficacious: bosentan (I); sildenafil (I); epoprostenol (I); treprostinil (I) Promising: beraprost (II) Aspiration pneumonitis None Gastrointestinal (75%–90%) Upper Efficacious: proton-pump inhibitors; histamine H2-receptor antagonists Lower Efficacious: domperidone (II); erythromycin (II); cisapride (II); octreotide (II) Renal (10%–15%) Hypertensive renal crisis Efficacious: angiotensin-converting enzyme inhibitors (II) * United States Preventive Services Task Force levels of evidence:5 I = at least one randomised controlled trial; II = well designed trial(s) without randomisation, or well designed case–control or cohort studies, or multiple time series with/without intervention; III = opinions of respected experts based on clinical experience; ?II = probably level II, but uncertain. † Percentages represent prevalence among all patients with systemic sclerosis. ‡ Non-specific interstitial pneumonitis, usual interstitial pneumonitis, bibasilar pulmonary fibrosis.

Helen J Englert MB BS, PhD, FRACP · Nicholas Manolios MB BS, PhD, FRACP

Clinical record A: Tattooed area of right arm, showing erythema, papules and nodules. B: Histopathology of skin biopsy from forearm, showing a poorly formed granuloma (arrow) (periodic acid–Schiff stain; original magnification, × 200). A 32-year-old Maori man presented with a 2-week history of worsening erythema, oedema and pain in parts of the recently acquired Maori tribal-style tattoos on his right arm and right lower leg. He developed a skin reaction, predominantly over the right cubital fossa, right thigh and calf. The reaction was unusual for such tattooing. Over a 2-month period he had had serial extensive tattooing to his thigh and arm at a Sydney parlour. The tattoos were all by the same artist, using the same pattern and ink colour. The patient was systemically well and had not experienced any fever. There was no history of immunocompromise and he was not taking any regular medication. When the lesions had first appeared, some 3 weeks after the tattoos had been done, he had presented to his general practitioner, who had treated him empirically with cephalexin, doxycycline and topical hydrocortisone 1%. When there was no improvement, he was referred for a dermatological opinion. On examination, the patient was exquisitely sensitive to light touch in the tattooed areas of the right cubital fossa, right upper thigh and calf. Erythema, oedema and violaceous nodules were present, but there was no ulceration or abscess formation and there were no palpable cords. Pulses were detectable, and there was no associated lymphadenopathy or nodular lymphangitis (Figure A). A skin biopsy from the forearm was sent for histopathology and culture (including deep fungi and mycobacteria). Histopathological examination showed an inflammatory infiltrate, most marked in the upper dermis, and poorly formed granulomas (Figure B). Mycobacterium chelonae was grown from the specimen cultures and was identified by both high-performance liquid chromatography and line probe assay at the reference laboratory at Westmead Hospital. Susceptibility testing by the agar disk diffusion technique (used to test rapidly growing mycobacteria such as M. chelonae and M. fortuitum1) showed susceptibility to clarithromycin; intermediate susceptibility to moxifloxacin, tobramycin and azithromycin; and complete resistance to all other agents, including minocycline, rifampicin, cotrimoxazole, imipenem, ciprofloxacin, cefoxitin and amikacin. Given the clinical context, our patient was assessed for associated comorbidities predisposing to an atypical mycobacterial infection. Serology testing for HIV, hepatitis B and hepatitis C was negative; blood sugar levels were normal; and a chest x-ray proved unremarkable. Because of the extensive skin surface area involved (about 10% of the body surface area), surgical excision was inappropriate and systemic antimicrobial therapy was warranted. As the organism was resistant to most antimicrobials, dual therapy with clarithromycin 500 mg twice daily and moxifloxacin 400 mg daily was commenced. The clarithromycin dose was increased to 1 g twice daily over a 4-week period. Antimicrobial therapy was continued for 4 months, resulting in significant clinical improvement. On clinical review, there was some residual nodularity and scarring but no evidence of recurrence of the infection. A repeat skin biopsy demonstrated no mycobacterial growth. Inspection of the tattoo parlour sourced the M. chelonae to a tattoo ink bottle that had been mixed using an industrial bolt that was left in situ. The same ink bottle had been used on multiple clients over a 2-month period. We are aware of three other clients who had similar reactions, including the index patient’s father. The tattoo parlour was referred on to the public health authorities. Fearing retribution, the patient did not wish to provide sufficient details to the public health unit for further investigation. Mycobacterium chelonae is a rapidly growing, non-tuberculous mycobacterium, classified as one of the Runyon group IV mycobacteria. A ubiquitous saprophyte in the environment, it has been found in soil, water, sewage and dust particles.2,3 In humans, the organism is an uncommon cause of localised cutaneous lesions (eg, associated with surgical wounds or acupuncture) and also disseminated disease.4,5 Often the source is contamination from colonised tap water, although there have been reports of contaminated tissue-marking agents used in surgery.6,7 M. chelonae infections most commonly occur in immunosuppressed patients, such as transplant patients, in whom disease can be progressive and disseminated. In this context, there should be a high index of suspicion for M. chelonae infection.8 Tattooing carries with it several medical risks, including transmission of infectious disease due to organisms such as hepatitis B virus, HIV, Treponema pallidum, papillomavirus, and typical or atypical mycobacteria.9,10 There have been case reports of cutaneous M. tuberculosis infection following inoculation by tattooing,11 but, to our knowledge, M. chelonae infection associated with tattooing has not been previously reported. In purely cutaneous disease, M. chelonae is introduced by trauma to the skin.12 The organism can also cause various clinical syndromes, including isolated lymphadenitis, osteomyelitis, joint infections, ocular disease and pulmonary disease. Lesions characteristically commence as red-to-violaceous subcutaneous nodules that may be painful and sometimes progress to cellulitis, abscesses or ulcers. Regional lymphadenopathy may be present,3 but constitutional symptoms are typically absent.7 Disseminated disease, usually originating from primary skin and soft tissue lesions, occurs almost exclusively in immunocompromised patients, such as those having solid organ transplants.13,14 Interestingly, in the case described here, the infection was only cutaneous and the patient was otherwise well. However, the case highlights the need to consider the possibility of systemic disease. Although there are no set guidelines for M. chelonae work-up, management of our patient warranted investigation for infectious diseases cotransmitted with tattooing as well as a chest x-ray to rule out pulmonary involvement.15 Treatment for M. chelonae infection is challenging, as the organism is resistant or only partially susceptible to many antibiotics. Based on sensitivities, and to avoid the emergence of resistance, dual treatment with clarithromycin and another antibiotic is recommended. Resistance to monotherapy with clarithromycin has been reported.8 Therapy often needs to be continued for several months, which can be difficult in terms of patient compliance.12 Because of the extensive skin surface area involved in this case, surgical excision of the affected skin was not appropriate. However, surgery may be a management option in cases in which there is abscess formation or in which drug therapy is difficult. Removal of any foreign bodies, such as iatrogenically introduced devices (eg, catheters, breast implants) is essential for management.15 Although cutaneous mycobacterial infections are uncommon, a high degree of suspicion is warranted when investigating skin lesions that do not respond to standard antimicrobial therapy. When assessing a patient with a tattoo reaction, M. chelonae infection should be considered in the differential diagnosis. Lessons from practice Mycobacterium chelonae is a ubiquitous microorganism and an uncommon cause of infection in humans. Most infections have been reported in immunocompromised patients. There should be a high index of suspicion for atypical pathogens in patients with skin lesions that do not respond to standard antimicrobial therapy. Investigations should include a diagnostic skin biopsy (in formalin) sent for histopathology and a fresh specimen sent for microscopy, culture and sensitivity testing. Sensitivity testing is essential to determine the most appropriate antimicrobial therapy. Although there is a high standard of public health regulation of tattoo parlours in Australia, cases such as these highlight the need to consider atypical pathogens as well as more common pathogens (eg, hepatitis C virus) in patients with suspected tattoo infections.

Veronica A Preda MB BS, BSc(Hons) · Michael Maley MB BS, FRACP, FRCPA · John R Sullivan MB BS(Hons), FACD

Objective: To explore the experiences of patients with acne, psoriasis or atopic eczema in their relationships with their treating doctors.Design: Qualitative study, using semi-structured interviews conducted between January 2004 and April 2005, thematic analysis and modified grounded theory methodology.Setting and participants: Participants were patients with acne, psoriasis or atopic eczema recruited from urban general practices and urban dermatology practices.Results: 62 semi-structured interviews were conducted. Reports of negative experiences with doctors treating participants’ skin conditions were common. Both general practitioners and dermatologists were reported as having poor comprehension of the psychological implications of skin diseases, being insensitive to their patients’ emotional suffering, and trivialising participants’ disease. Participants acknowledged that time considerations and other pressures may explain these apparent deficiencies. Some participants perceived their doctors as medical technicians and sought treatment for their physical skin disease, not for its emotional or social aspects.Conclusion: We recommend education for GPs about the psychological effects of skin diseases, and education for dermatologists and GPs on how to elicit and manage, or appropriately refer, these problems.

Parker J Magin PhD, DPD, FRACGP · Jon Adams MA, PhD · Gaynor S Heading BA, GradDipHSS(MSS), PhD · C Dimity Pond MB BS, PhD, FRACGP

To the Editor: In addition to its well established link with rickets and osteoporosis, vitamin D deficiency has been associated with increased risk of autoimmune, malignant and cardiovascular disease.1 Marginal deficiency occurs at serum 25-hydroxyvitamin D [25(OH)D] levels of 25–50 nmol/L and frank deficiency at levels < 25 nmol/L,2 but there is some evidence that levels < 80 nmol/L3 or even < 110 nmol/L2 could be suboptimal. In Australia, vitamin D deficiency is most frequent in nursing home residents, dark-skinned veiled women, and residents of southern latitudes.2 However, those who are instructed to habitually minimise sun exposure following a diagnosis of skin cancer may also be at particular risk. We recruited patients with a history of non-melanoma skin cancer, who were not taking vitamin D or calcium supplements, from outpatient dermatology clinics at Royal Prince Alfred Hospital, Sydney (latitude, 33° south). Ethics approval was obtained from the Sydney South West Area Health Service and University of Sydney ethics committees, and all participants provided written informed consent. Serum 25(OH)D levels were measured by radioimmunoassay (DiaSorin, Saluggia, Italy)4 in both late summer (February 2006 or 2007) and late winter (August 2006), with participants completing a 2-week diary detailing daily sun exposure and sunscreen application before each measurement. Twenty-five participants (12 men, 13 women; mean age, 64 years; range, 44–78 years) completed both assessments. We found a significant reduction in mean 25(OH)D levels in winter (summer, 69 ± 3.4 nmol/L; winter, 59 ± 6.2 nmol/L; P < 0.05). In summer, all but one participant had 25(OH)D levels > 50 nmol/L, and eight had levels > 80 nmol/L. In winter, 12 participants had 25(OH)D levels < 50 nmol/L, two had levels < 25 nmol/L, and only three had levels > 80 nmol/L (Box). Hence, using the accepted target value of 50 nmol/L,2 12 participants (48%) were vitamin D-deficient at the end of winter, compared with one (4%) at the end of summer. In summer, the mean reported daily sun exposure was 1 hour (range, 10 min–2.5 h), comprising 40 minutes of off-peak (before 11 am or after 3 pm) and 20 minutes of peak exposure. In winter, the mean daily exposure was also 1 hour (range, 20 min–1.5 h), comprising 30 minutes each of both peak and off-peak sunlight. Volunteers reported wearing sunscreen during about 50% of their summer sun exposure and 27% of their winter sun exposure. Despite mean reported daily sun exposure falling within recommended guidelines, half of our participants were vitamin D-deficient at the end of winter, with almost all demonstrating reductions in winter 25(OH)D levels. Our findings suggest that vitamin D deficiency may be much more prevalent than expected in these patients, and that vitamin D supplementation might be indicated for this group, at least during winter. Vitamin D levels in summer and winter 25(OH)D = 25-hydroxyvitamin D.

Anna-Marie McCombie · Rebecca S Mason · Diona L Damian

To the Editor: A number of commentaries and articles have been published recently about the ability of doctors working in primary care skin cancer clinics to diagnose and manage skin cancer.1-3 However, limited information has been published comparing the patient populations that attend the different service providers (ie, “traditional” general practitioners versus doctors at skin cancer clinics). In 2005, we conducted a large population-based survey of Queensland residents aged 20–75 years to examine the prevalence of behavioural risk factors for cancer and current cancer screening practices.4 Using data from our study, we examined the prevalence of clinical skin examination and identified factors associated with choice of service provider. A total of 9419 respondents completed the interviews (response rate, 45.6%). Complete data for this analysis were available for 5499 of the respondents, of whom 48.2% were men. Thirty per cent of respondents reported they had had a general check of all or nearly all of their body in the previous 12 months. Factors associated with an increased likelihood of having a whole-body skin examination in the previous 12 months included being male (odds ratio [OR], 1.15 [95% CI, 1.00–1.31]), being 60–75 years of age (reference group, 20–39 years) (OR, 1.73 [95% CI, 1.45–2.07]) and having an annual gross income of ≥ $60 000 (reference group, < $20 000 annual gross income) (OR, 1.42 [95% CI, 1.18–1.71]). The strongest predictors were a self-reported history of melanoma (OR, 2.68 [95% CI, 2.01–3.57]) or non-melanoma skin cancer (OR, 2.01 [95% CI, 1.65–2.45]). No associations were seen between choice of service provider and any sociodemographic variables, including sex and age group. Additionally, skin cancer risk factors (such as having highly sensitive skin or a history of melanoma) did not make respondents any more or less likely to attend either a GP or a skin cancer clinic doctor. Various reasons were given by respondents for their choice of service provider (Box). Skin cancer clinics appeared to be chosen primarily because they offered bulk-billing or because respondents just wanted a general skin check. Traditional GPs were more likely to be chosen for convenience or because of concern about a specific spot or mole. Skin cancer is a major public health issue, and the provision of adequate and appropriate clinical services is a continuing and growing challenge. We found that a significant proportion of the Queensland population had undergone a whole-body skin examination by a doctor within the previous 12 months, and that those attending appeared to be the group most at risk of developing skin cancer. We did not find any significant differences in the profiles of those who chose a skin cancer clinic or a general practice for their skin examination. Reasons given for choice of service provider* by 2895 respondents who had had some type of skin check in the previous 12 months† * General practitioner or skin cancer clinic doctor. † Percentages do not total 100 due to multiple responses.

Philippa H Youl · Peter D Coxeter · David C Whiteman · Joanne F Aitken

Objective: To determine the association, if any, between male-pattern hair loss (baldness) and serum 25-hydroxyvitamin D (25-OHD) levels.Design and participants: A cross-sectional study of 296 healthy middle-aged and older men.Main outcome measures: Degree of baldness was independently assessed by two researchers using the Hamilton–Norwood scale and serum 25-OHD was measured in all men.Results: Classification of the degree of baldness by the two researchers showed a high level of agreement (κ = 0.93). Forty-eight per cent of men had no hair loss or mild frontotemporal recession, 15% had predominant vertex loss, and 37% had significant scalp and vertex loss. After data were adjusted for potential confounding factors — including age, month of 25-OHD measurement, exercise levels, use of sunscreen, skin type and frequency of outdoor hat wearing — no significant differences in 25-OHD levels between these groups was detected (P = 0.60).Conclusions: The degree of baldness does not appear to influence serum 25-OHD levels. The high prevalence of baldness in older men does not explain sex differences in 25-OHD levels. Other novel hypotheses are required to help determine whether baldness serves any physiological purpose.

Mark J Bolland MB ChB, PhD · Ruth W Ames NZCS · Andrew B Grey MD · Anne M Horne MB ChB · Barbara H Mason BSc · Greg D Gamble MSc · Ian R Reid MD

To the Editor: Kaposi’s varicelliform eruption (KVE) is a disseminated cutaneous infection caused by herpes simplex virus (HSV) in patients with predisposing factors such as atopic dermatitis, widespread skin injury and sun exposure.1-5 I report a patient with KVE but no apparent predisposing factors. A 54-year-old man presented with a 3-day history of a rapidly progressing vesiculopustular rash on his trunk, legs, arms and hands (Box). He reported a burning skin sensation and had a temperature of 38.2°C. He had no labial or oral erosions, and no history of skin disease, HSV infection or any systemic disease. He was not taking any medication and reported no excessive sun exposure before symptom onset. Haematological, biochemical and immunological parameters, including levels of C-reactive protein, immunoglobulins, complement components, lymphocyte blastogenesis and natural killer cell cytolytic activity were normal. An HIV test was negative. Skin swabs from the lesion were positive for HSV-1 by polymerase chain reaction (PCR) testing; HSV-1 was also isolated on culture. Cultures were negative for bacterial, fungal and mycobacterial pathogens. A diagnosis of KVE was thus established. Based on past experience treating KVE with a combination of oral valaciclovir and vidarabine ointment, which accelerated resolution of symptoms,6 I treated the patient with oral valaciclovir (1 g three times per day) and vidarabine ointment (three times per day). The lesions were completely healed after 7 days of treatment. HSV-1 antibody titres on Days 1 and 7, respectively, were: IgM, 3.1 and 5.2 (reference range, < 0.8); and IgG, < 2.0 and 4.7 (reference range, < 2.0). HSV-2 IgM and IgG antibody titres on Days 1 and 7 were within reference ranges (< 0.8 and < 2.0, respectively). This case is unusual as it occurred in an otherwise healthy patient. KVE is usually associated with healing second-degree burns, peribuccal dermabrasion and laser skin resurfacing,2-4 and sun exposure in patients with recurrent HSV infection.5 The origin of the patient’s HSV-1 infection was not identified: there was no outbreak of HSV infection in his city of residence; his wife and two children were healthy and had no systemic or skin diseases; PCR testing of their saliva for HSV-1 and HSV-2 DNA 3 days after the patient’s presentation gave negative results; and the patient had no apparent contact with HSV-infected patients before onset of symptoms. KVE has been successfully treated with intravenous aciclovir (three times per day) or oral aciclovir (five times per day).2,5 However, intravenous aciclovir requires hospital admission, and compliance with the dosage regimen of oral aciclovir is troublesome. In contrast, oral valaciclovir (three times per day) and vidarabine ointment do not require hospital admission and are easier for patients.1,3,6 Oral valaciclovir is also very effective for preventing herpes infection.7 This case highlights that KVE should be considered in otherwise healthy patients with a sudden, rapidly progressing vesiculopustular rash. Vesiculopustular lesions in a patient with Kaposi’s varicelliform eruption

Hajime Kimata

Leading international health organisations are concerned about high use of artificial tanning services and the associated risk of skin cancer. Similar concerns exist about the growing Australian solarium industry. Pre-teens appear to be ignoring sun safety messages in their desire to tan and use solaria. A significantly elevated risk of melanoma exists among people exposed to artificial ultraviolet radiation; the risk is higher for those younger than 35 years at first solarium use. For all users, the risk of squamous cell carcinoma is more than doubled compared with non-users. We estimated the numbers of new melanoma cases and melanoma-related deaths attributable to solarium use by younger people in the five most populous Australian states and indirectly quantified potential costs to the health system that could be saved by effective regulation of the solarium industry. Annually, 281 new melanoma cases, 43 melanoma-related deaths and 2572 new cases of squamous cell carcinoma were estimated to be attributable to solarium use. The annual cost to the health system — predominantly Medicare Australia — for these avoidable skin cancer cases and deaths is about $3 million. By successfully enforcing solarium regulations that ban use by people younger than 18 years or with fair skin, favourable health and cost benefits could be expected.

Louisa G Gordon MPH, PhD · Nicholas G Hirst BComm, BEc · Peter H F Gies PhD · Adèle C Green MB BS, PhD

Clinical record A 44-year-old Samoan man presented in 2004 with a blistering skin rash affecting his face, trunk and upper limbs (Figure, A). There was no mucosal involvement and a positive Nikolsky sign (the production of a blistering lesion on applying pressure to non-affected skin) was demonstrated. Skin biopsy revealed acantholysis and cleft formation within the superficial layers of the epidermis, confirming a diagnosis of pemphigus foliaceus. Direct immunofluorescence testing of a perilesional skin biopsy specimen revealed deposition of IgG and C3 in the intercellular cement substance of all layers of the epidermis. Indirect immunofluorescence testing, using a monkey oesophagus substrate, demonstrated a high titre of autoantibodies in the patient’s serum. The condition failed to respond to prednisone combined with other immunosuppressive agents, including azathioprine, cyclosporin and mycophenolate mofetil. In late 2006, the patient developed a significant flare of the disease, associated with Staphylococcus aureus superinfection, which resulted in a lengthy hospital admission. Plasmapheresis was instituted, with clinical benefit and a concomitant decrease in antipemphigus antibodies to undetectable levels. However, the plasmapheresis was complicated by Citrobacter koseri sepsis due to colonisation of the intravenous catheter. Despite treatment of the sepsis and reinstitution of immunosuppression with prednisone and mycophenolate mofetil, the pemphigus flared again, accompanied by a dramatic increase in the titre of antipemphigus antibodies. The hospital drug committee approved off-label use of two courses of rituximab (375 mg/m2). This resulted in rapid resolution of the lesions and a marked decrease in antipemphigus antibodies. Depletion of B cells was evident on immunophenotyping of peripheral blood mononuclear cells, and the corticosteroid dose was subsequently weaned to 0.1 mg/kg/day. Nine months after treatment with rituximab, the patient’s clinical condition remained stable (Figure, B). Autoimmune blistering diseases are rare but potentially life-threatening.1 Pemphigus foliaceus is characterised by superficial erosion of the skin without mucosal involvement. The disease is mediated by autoantibodies directed against desmoglein-3,2 a structural protein involved in epidermal cell adhesion. The levels of these pathogenic autoantibodies can be measured by indirect immunofluorescence and, as illustrated in our patient, are useful for monitoring disease activity.2 The combination of prednisone and azathioprine is often used as first-line therapy,3 but other immunosuppressive agents, as well as intravenous immunoglobulins and plasmapheresis, have also been used to control disease activity.4 However, these therapies do not induce remission in all cases and they can be associated with significant adverse events. Lessons from practice Blistering skin diseases are potentially life-threatening and can have an autoimmune basis. Direct immunofluorescence of a perilesional skin biopsy is essential for diagnosis. Titres of autoantibodies in the patient’s serum, measured by indirect immunofluorescence, are useful for monitoring disease activity. Rituximab can be used successfully for the treatment of severe, refractory pemphigus foliaceus. Rituximab is a chimeric (human/murine) monoclonal antibody directed against CD20, a cell surface molecule specific to B cells. Although it was initially approved for use in B-cell non-Hodgkin’s lymphoma, a growing number of reports have described the efficacy of rituximab for B-cell depletion in the treatment of autoimmune diseases.5 The mode of action of rituximab in autoimmune diseases may include removal of the precursors of autoantibody-producing plasma cells and impairment of autoantigen presentation to T cells.6 A recent case series showed that rituximab induced remission in 18 of 21 patients with pemphigus, whose condition had not responded or who had contraindications to corticosteroid therapy. The treatment was generally well tolerated; however, two cases were complicated by severe infection, one resulting in death.7 Ongoing surveillance of patients treated with rituximab for pemphigus and other autoimmune diseases is required to monitor long-term complications. A recent review of the increasing use of rituximab for off-label indications in a large teaching hospital highlighted the need for a database to help determine optimal dosing regimens and to record clinical outcomes.8 In our patient, two infusions of rituximab resulted in depletion of peripheral B cells, a reduction in the level of circulating antipemphigus autoantibodies and remission of disease over a 9-month follow-up period. Hence, rituximab may be a suitable alternative for patients with pemphigus who have refractory disease or contraindications to first-line immunosuppressive therapy.

Suran L Fernando PhD, FRACP, FRCPA · Kate S O’Connor MB BS

A 79-year-old woman presented with a 3-month history of rapid growth of multiple long, thin, non-pigmented hairs, distributed diffusely over the entire body, preferentially on the face and trunk (Figure, A). After extensive investigations, two neoplasms were detected — a breast mucinous carcinoma and a metastatic endometrial carcinoma (Figure, B) — establishing the diagnosis of paraneoplastic hypertrichosis lanuginosa acquisita. Acquired hypertrichosis is strongly associated with underlying neoplasm (mainly lung and colorectal cancer).1,2 Therefore, detailed and extensive investigations are mandatory to detect the associated malignancy and to allow early and specific therapy. B: Pelvic magneticresonance imagingrevealed anendometrial tumour(arrow) and multipleenlarged lymph nodes (asterisks)

Marta Ferran · Montserrat Gilaberte · Josep E Herrero-Gonzalez · Lara Pijuan · Ramon M Pujol

A 14-year-old boy was admitted with a 2-week history of increasing breathlessness and fatigue. He had a pulse rate of 130 beats/min and blood pressure of 100/66 mmHg with 16 mm paradox. Jugular venous pressure was raised 10 cm above the sternal angle, and heart sounds were faint. He had been diagnosed with refractory iron-deficiency anaemia in early childhood, for which he had been receiving blood transfusions. He denied any history of epistaxis, haemoptysis, malaena, haematuria or overt bleeding from any other site. On examination, the patient had multiple, blue-black, papular and nodular, compressible, non-pulsatile, vascular skin lesions, ranging in size from a few millimetres to 1–2 cm, distributed over the trunk and limbs, including the soles of the feet, perineal region (Figure A) and lips. A chest x-ray showed an enlarged cardiac silhouette suggestive of pericardial effusion (Figure B). This was confirmed by transthoracic echocardiography. Therapeutic pericardiocentesis showed haemopericardium. Blue rubber bleb naevus syndrome (Bean syndrome) is diagnosed in the presence of distinctive venous malformations on the skin, in the gastrointestinal tract and, less often, in other organs, leading to occult or overt gastrointestinal bleeding and chronic anaemia.1-3

Pankaj Malhotra · Madhav C Menon · Subramaniyan S Anand · Arshjyot Narula · Subhash Varma

To the Editor: In a recent article, Youl and colleagues provided information about the ability of doctors to accurately diagnose skin lesions that they excise or biopsy.1 We wish to offer some comments about their comparison between general practitioners and skin cancer clinic doctors. First, in the study by Youl et al the behaviour of GPs and patients in mainstream practice was different from that of doctors and patients in skin cancer clinics, as indicated by the comparative frequency of whole body skin examinations performed (GPs, 30.4%; skin cancer clinic doctors, 73.2%).1 The study did not indicate the circumstances under which each decision to excise took place. Did patients become aware of a new or changing skin lesion and bring it to the attention of the doctor, or did the diagnosis result from a whole body skin check that might have revealed an earlier, previously unnoticed and more subtle lesion? It may be useful to separate basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) into histological subtypes, as early superficial BCC and intraepidermal SCC may be more difficult to diagnose than other subtypes.2 Second, the casemix of non-melanotic skin cancers in the two groups of doctors was quite different, with a BCC : SCC ratio of 1.1 : 1 for GPs and 2.1 : 1 for skin cancer clinic doctors. The difference in casemix was reflected in a study of our own3 in which we described the histology of 1247 lesions excised by doctors, including 76 lesions removed by one doctor in a designated skin cancer clinic. In an unpublished sub-analysis, we divided the results into two settings for comparison (Box). Like Youl et al, we found that the casemix of non-melanotic skin cancers was significantly different for the two groups of doctors (P < 0.001), but in our study the BCC : SCC ratio was much higher for skin cancer clinic doctors (4 : 1) than for GPs (0.6 : 1). We believe this most likely reflects an increased pick-up of BCC in skin cancer clinics, owing to the higher frequency of full body skin examinations and the consequent detection of lesions of which the patient is unaware. Third, the reported sensitivity and specificity in the study by Youl et al refers only to excised lesions. There is no information given about the lesions that practitioners decided not to excise. The sensitivity and specificity of skin examinations can only be determined if all relevant skin lesions are assessed, thereby giving an accurate representation of the number of true- and false-negative diagnoses. However, this would require multiple excisions, which would be clinically unacceptable. An important limitation of the study is that it does not assess or compare how many skin cancers each group of doctors missed. In conclusion, although the study by Youl et al provides comprehensive information about diagnostic accuracy, we do not feel — based on the information available — that a meaningful comparison between the two groups of doctors can be made. Comparison of lesion excisions in skin cancer clinic and general practice settings Mean patient age (years) Proportion of excised lesions that were malignant* BCC : SCC ratio Number needed to treat† Skin cancer clinic 56.5 76% (58/76) 4 : 1 (44/11) 4.7 (14/3) General practice 56.9 45% (512/1145)‡ 0.6 : 1 (190/305) 9.0 (154/17) BCC = basal cell carcinoma. SCC = squamous cell carcinoma. * BCC, SCC or melanoma. † Benign or dysplastic naevi excised per melanoma. ‡ There were 26 cases in which histology results were missing. All were in the general practice setting.

Clare Heal · Beverly Raasch

To the Editor: Youl and colleagues are to be commended for their research into the performance of special-interest skin cancer clinicians.1 However, the conclusion that the performance of general practitioners and skin cancer doctors in the diagnosis of skin cancer is similar is highly questionable. To truly compare the two groups and their diagnostic accuracy, it must be established that the participants were representative of the groups they are supposed to represent. The fact that the participating GPs were largely self-selected, perhaps on the basis of their personal interest in the subject, was a potential flaw that the authors acknowledge. Further, an examination of diagnostic accuracy should also take into account whether the lesions found were of similar type, size and stage. There was no determination of any qualitative differences (eg, in size or thickness) between the tumours seen and diagnosed by the two groups. When a patient presents, specifically, with a large, tender, hyperkeratotic squamous cell carcinoma (SCC), there is no real test of diagnostic skills. On the other hand, detecting a small early posterior-thigh melanoma or a superficial BCC on a whole body examination is a challenge. Overall, one would expect at least two to three BCCs to be diagnosed for each SCC found2 — however, in the study by Youl et al, GPs found a similar proportion of each type of lesion, suggesting that perhaps a large number of BCCs were not being detected at all in the GP group. The lower incidence of whole body examinations in the GP group suggests that a higher proportion of asymptomatic lesions may have been missed by the GP group and thus not included in their sensitivity/specificity data. This possibility could have been examined by noting the site of lesions found: identification and diagnosis of lesions in areas covered by clothing or footwear may be more likely on whole body examination. Although Youl et al reported that the diagnostic sensitivity for melanoma among skin cancer clinic doctors was twice that of GPs, a re-examination of the data with all of the above in mind may well reveal that skin cancer clinic practitioners are performing even better than suggested. That being said, the number of melanomas found per week by the skin cancer group (0.25 melanomas/doctor/week) in the study by Youl et al is much lower than in our own dedicated primary care skin cancer clinic (1.47 melanomas/doctor/week, based on audit data gathered between February and September 2007). Good medical care relies on accurate diagnosis and appropriate treatment, and the earlier the diagnosis is made, the less costly and less invasive the treatment and the greater likelihood of a cure. Surely we should all be working together — skin cancer clinic practitioners and GPs, alike — towards achieving optimum outcomes for our patients. To that end, a wider range of higher education in skin cancer medicine is being encouraged by the University of Queensland’s Master of Medicine program3 and the Skin Cancer College of Australia’s fellowship program,4 and bodies such as the Skin Cancer Society of Australia and the Royal Australian College of General Practitioners have been working together to introduce an accreditation process for those practising primary care skin cancer medicine.5,6

Jeffrey Keir

In reply: We thank Heal and Raasch, and Keir for their comments and suggestions. First, as acknowledged in our article, it is possible that general practitioners with an interest in skin cancer may have been over-represented in our sample. It is also the case that the comparison between GPs and skin cancer clinic doctors may have been affected by characteristics of patients attending each type of practice. Patients attending skin cancer clinics are self-selected (often worried about a specific skin lesion), while for those attending GPs in mainstream practice, skin lesions are more likely mentioned during a consultation for something else.1 Case selection, which helps increase diagnostic ability by Bayesian principles (improving pretest probability of malignant lesions), may thus be more likely for skin cancer clinic doctors than GPs.2 Our study represented a broad cross-section of skin cancer clinics, and the number of melanomas excised per doctor per week ranged from 0 to 1.7. The ratio of basal cell carcinomas to squamous cell carcinomas excised ranged from 0.1 to 6.0 for mainstream GPs and 0.8 to 8.0 for skin cancer clinic doctors. Whether clinical and histological features of skin lesions or the type of skin examination undertaken influence diagnostic accuracy was beyond the scope of our initial study. This question will be the subject of future analyses. It has been suggested that a limitation of our study was that it did not assess or compare the number of skin cancers each group missed. However, as specifically stated in our article, the aim of our study was to examine diagnostic accuracy of excised or biopsied lesions. To examine the sensitivity and specificity of all lesions (excised and non-excised) and of screening examinations would require a different study design. We disagree that meaningful comparisons between the two groups cannot be made from the data collected in our study. Our prospective study included over 11 000 skin excisions or biopsies from a large group of mainstream GPs and from doctors working in a variety of skin cancer clinics. One of the most important outcome measures of our study was the degree of accuracy of skin cancer diagnoses within the primary care setting. We have demonstrated that primary care practitioners, whether mainstream GPs or skin cancer clinic doctors, diagnose skin cancer with similar, high levels of accuracy. This is a reassuring result, particularly in a country with the world’s highest incidence of skin cancer.

Philippa H Youl · Peter D Baade · Monika Janda · Christopher B Del Mar · David C Whiteman · Joanne F Aitken

A 64-year-old man was referred for assessment of a symmetric violaceous rash of the dorsal aspect of the fingers (Figure, A), trunk, olecranon processes and malleoli. An oedematous, blue-purple discolouration of the eyelids was also apparent. The patient complained of severe weakness of the proximal muscles and dysphagia. T2-weighted magnetic resonance imaging showed muscular inflammation and a pulmonary mass (Figure, B) that was histologically identified as squamous cell carcinoma and staged as T3 N0 M0. The dermatomyositis, confirmed by elevation of serum muscle enzymes and electromyography, improved clinically with oral prednisone plus hydroxychloroquine, and did not recur after surgical excision of the tumour. A: Symmetrical violaceous rash with papules on the dorsal aspect of the interphalangeal and metacarpophalangeal joints. Cuticle telangiectasias can also be seen. B: T2-weighted magnetic resonance image showing marked swelling and diffuse dyshomogeneity of skeletal muscles (thick arrows), a 4 cm peripheral mass in the upper lobe of the right lung (thin arrow) and bilateral pleural effusion (arrowheads).

Daniele Torchia · Emiliano Antiga · Letizia Ricupero · Marzia Caproni · Paolo Fabbri

To the Editor: A 30-year-old man presented with pain, swelling and discharge from lesions on his left arm. He had undergone extensive tattooing on the arm 3 days earlier at a commercial tattoo operation, where single-use needles were used, with initial drawing of lines followed by additional shading. The patient complained of severe neuropathic pain in the arm, which was greater than would be expected from uncomplicated bacterial cellulitis. He did not give a history of oral or genital herpes and had previously been tattooed without complication. On presentation, the patient had a low-grade fever (37.9°C), a heart rate of 80 beats/min and blood pressure of 130/80 mmHg. He had no neurological deficit. Vesicular lesions were visible in the region of the tattoo marks, predominantly affecting areas of shading and with minimal spread outside tattooed areas (Box). A bacterial swab of the lesions grew methicillin-sensitive Staphylococcus aureus, and a polymerase chain reaction test of vesicular fluid was positive for herpes simplex virus type 1 (HSV-1). The patient was commenced on intravenous flucloxacillin (1 g four times daily) and oral famciclovir (250 mg three times daily). He required ongoing inpatient management for pain relief. Five days after development of the lesions, HSV-1 serology demonstrated positive results for IgM and IgG. An HIV test was negative. The patient’s lesions slowly resolved, and he was discharged 7 days after admission. Most concerns regarding infectious complications of tattooing have focused on transmission of blood-borne viruses, but superficial infections with other pathogens have also been described.1 The personal care and body art industries are regulated in Australia to minimise the transmission of blood-borne infection,2 and most state and territory authorities also publish infection control guidelines. Herpes dermatitis is often confused with bacterial infection, although co-infection may occur. This distinction is clinically important, as antibiotics and surgical debridement are not usually required for herpetic infections, and herpetic lesions may recur. Secondary herpetic infection complicating skin disease is most commonly associated with eczema (eczema herpeticum) or other skin diseases (Kaposi’s varicelliform eruption), and minor skin trauma, such as in herpetic whitlow or herpes gladiatorum.3,4 We are not aware of any previous reports of herpetic infection complicating tattoo placement. The distribution of herpetic lesions in our patient suggested that the needle used for tattoo shading became contaminated with HSV-1 during the course of tattoo placement, but it is also possible that superinfection occurred through damaged skin after the procedure. We propose the term “herpes compunctorum” to describe this condition. Vesicular lesions on patient’s tattooed forearm

Catherine S Marshall · Felicity Murphy · Shannon E McCarthy · Allen C Cheng

As practice continues to evolve, there will need to be concurrent changes in undergraduate and postgraduate medical education on skin cancer Over the past two decades, preventive health programs about the need for sun protection have alerted patients to the significance of increased rates of skin cancer in white Australians. Skin checks of both affected people and the “worried well” have become daily medical practice. This public demand has resulted in changes to medical practice and an increase in associated health costs, as touched on in two other articles in this issue.1,2 In this editorial, I argue that, as practice continues to evolve, there will be a need for concurrent changes in undergraduate and postgraduate medical education on skin cancer. Each year over 300 000 Australians are diagnosed with melanoma or non-melanoma skin cancer.3 However, on clinical examination, it is not always easy to tell the difference between benign lesions and skin cancer, even with specialist training. Both patients and medical practitioners feel the pressure to excise lesions if there is doubt about their malignancy. In this issue of the Journal, Youl et al report that a quarter of the number of lesions removed were as a result of patient insistence.1 For every melanoma excised, about 20–25 benign pigmented lesions are excised,1,4 amplifying surgical and pathology costs — nearly 300 000 benign naevi were excised over the period July 2005 to June 2006.5 Further, Askew et al demonstrate that skin cancer excisions are increasingly associated with complex and expensive surgical repairs.2 Medicare Australia statistics show that procedural cryotherapy for 10 or more solar keratoses was performed 595 568 times between July 2005 and June 2006.5 Skin cancer has been reported as the costliest of all cancers to treat.6 Traditionally, actinic lesions were initially managed by general practitioners, with appropriate referral to dermatologists, surgeons and radiotherapists. If GPs were uncertain about skin cancer diagnoses, they would refer patients to specialist dermatologists, who often had long waiting lists, were variably accessible, and charged higher fees. The Australasian College of Dermatologists (ACD) has long recognised the skin cancer “epidemic” in Australia, but has had difficulty meeting patient demand for dermatologists’ services, even with a trebling of the number of trainees from 20 in 1976 to 65 in 2006 (ACD, unpublished data). With a minimum 4-year training scheme, the number of practising Australian dermatologists has only risen from 136 in 1976 to about 350 in 2006 (ACD, unpublished data). Most people in metropolitan areas will have to wait for weeks or months to see a dermatologist, while access to dermatologists in rural and regional Australia is variable. The College’s state facilities have created regional outreach clinics with rostered dermatologists, but services still need to be improved. The two-tier relationship between GPs and specialists has been challenged recently by the rapid growth of skin cancer clinics that bulk-bill patients and are staffed by non-specialist medical practitioners.7 There are no regulations about who can set up these clinics — some are part of large commercial corporations. Nor are there any particular requirements for training of the clinicians who work there. Thus, an under-regulated three-tiered system of skin cancer management has developed. From the patient’s point of view, the convenience, accessibility and billing arrangement of these clinics may be appreciated. But, patients may also be incorrectly assuming that the attending medical practitioners have had “specialist training” and be unaware that their usual GP may be just as competent.1 From a professional perspective, some skin cancer clinicians, realising that they may have a “credibility” issue with their colleagues, have started to form liaisons with universities to establish accreditation courses. These clinicians are the “standard bearers”, but we need to know the competence of all clinicians in all skin cancer clinics, which should be open to examination by the public and professional peers. In my view, the rise of skin cancer clinics and the partial “sidelining” of GPs in skin cancer management is due not only to the relative shortage of specialist dermatologists but also to a failure in undergraduate and postgraduate education on skin cancer. In the 1980s and 1990s, I believe there was a profound, long-term underinvestment in the number of Australian medical schools, accompanied by variability in the breadth and quality of teaching on skin cancer. Over the next few years, owing to the development of new medical schools, the number of medical students graduating each year will almost double.8 Ensuring that skin cancer education is adequate will be an enormous challenge. Given the high prevalence of skin cancer in Australia, the Australian Medical Council should ensure that universities can sign off their graduates as competent in clinical recognition of skin cancers, as all interns will need this skill. This education needs to be significantly patient-based, to ensure that medical students have the chance to develop an appreciation of subtle clinical features. Available resources, including teachers as well as patients, are limited. New paradigms, educational technologies and collaborations will need to be established quickly.9,10 Going beyond basic recognition of lesions, skin cancer management is a complex issue, involving both procedural and pharmaceutical interventions. This requires supervised training, which should be undertaken by postgraduate clinicians who want to manage skin cancer. At the moment, further training for non-dermatologists who wish to increase their skills in this area is extremely ad hoc. Some universities have recently capitalised on the interest in skin cancer management by establishing skin cancer courses for medical postgraduates.7 These vary from weekend diagnostic certificate courses to year-long masters degrees, but, critically, may lack a significant component of face-to-face clinical contact with patients. While such courses may form an important part of future postgraduate skin cancer education, I believe the first priority of universities must remain the provision of undergraduate education. A different approach would be to look at more “hands-on” clinical training to achieve clinical competence in skin cancer management. The Royal Australian College of General Practitioners, the Australian College of Rural and Remote Medicine, and the ACD are working on a unique training and education scheme that will provide supervised clinical attachments and assess competence, but this program will take years to provide enough certified GPs. In the meantime, other GPs are establishing and publishing their credentials to manage skin cancer.2,3 There may be little difference in outcomes between competent experienced GPs and skin cancer clinicians.1 Public health studies have ensured that we are now aware that skin cancers are five times more common than all other cancers combined.6 Now the public needs to be assured that new medical graduates are able to recognise skin cancers and that postgraduate education institutes will ensure that clinicians who choose to treat skin cancer are appropriately trained and competent.

Christopher A Commens MB BS, FACD

Objective: To measure and compare the casemix and diagnostic accuracy of excised or biopsied skin lesions managed by mainstream general practitioners and doctors within primary care skin cancer clinics.Design, setting and participants: Prospective comparative study of 104 GPs and 50 skin cancer clinic doctors in south-eastern Queensland, involving 28 755 patient encounters. The study was conducted in 2005.Main outcome measures: Prevalence of each type of skin lesion; sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the clinical diagnosis against histology; number needed to excise or biopsy (NNE) for a diagnosis of skin cancer.Results: GPs excised or biopsied 3175 skin lesions (mean 2.5/week) including 743 basal cell carcinomas (BCCs) (23.4%), 704 squamous cell carcinomas (SCCs) (22.2%) and 49 melanomas (1.5%). Skin cancer clinic doctors excised or biopsied 7941 skin lesions (mean 34/week), including 2701 BCCs (34.0%), 1274 SCCs (16.0%) and 103 melanomas (1.3%). Overall, sensitivity for diagnosing any skin cancer was similar for skin cancer clinic doctors (0.94) and GPs (0.91), although higher for skin cancer clinic doctors for BCC (0.89 v 0.79; P < 0.01) and melanoma (0.60 v 0.29; P < 0.01). The overall NNE was similar for skin cancer clinic doctors (1.9; 95% CI, 1.8%–2.1%) and GPs (2.1; 95% CI, 1.9%–2.3%). This did not change after adjusting for years of clinical experience.Conclusions: GPs and skin cancer clinic doctors in Queensland treat large numbers of skin cancers and diagnose these with overall high sensitivity. The two groups diagnosed skin cancer with similar accuracy.

Philippa H Youl MPH · Peter D Baade PhD · Monika Janda PhD · Christopher B Del Mar MD · David C Whiteman PhD · Joanne F Aitken PhD

To the Editor: Menzies’ recent editorial1 highlights the clear benefits of dermoscopy in the assessment of pigmented lesions. This is well appreciated by anyone who uses this inexpensive handheld tool on a day-to-day basis (its retail price ranges from A$380 to A$1840). Although the potential value of the device has been documented in both specialist and general practice settings, it would seem that most Australian general practitioners aren’t using this valuable technology. We recently surveyed 223 predominantly Victorian GPs (at a dermatology symposium for GPs, Melbourne, August 2006) and a cross-section of 179 Australian dermatologists (at the 39th Annual Scientific Meeting of the Australasian College of Dermatologists, Melbourne, May 2006) on their use and perceptions of the value of dermoscopy (Box). The surveys were conducted at the end of dermoscopy seminars using electronic keypads that generated live feedback to questions posed. The sample of dermatologists represented about 56% of all practising fellows of the Australasian College of Dermatologists and should thus be reasonably representative. On the other hand, we acknowledge that the sample of GPs may have been biased towards those with a particular interest (and more experience) in the area of skin cancer and dermatology — or, alternatively, biased towards novice GPs seeking more experience in the area. Participation rates in each survey were over 90%. The majority of both groups of clinicians who reported using dermoscopy felt that it influenced their clinical diagnosis. However, only a third of GPs reported using dermoscopy as a diagnostic aid, in contrast with the vast majority of dermatologists (95%), who were regular users. While there was a difference between the instrument preferred by GPs (the Welch Allyn EpiScope [Welch Allyn Inc, Skaneateles Falls, NY, USA]) and by dermatologists (the Heine Delta 20 Dermatoscope [Heine Optotechnik, Herrsching, Germany]), any one of the commercially available dermoscopes would be suitable for the novice user. The popularity of the Heine system is mostly due to its brighter light-emitting-diode illumination and adaptability to compact digital cameras. Although there is a general perception that non-polarised immersion contact dermoscopes offer superior imaging (this was reflected in the most popular choices from our survey), newer polarised non-contact dermoscopes are increasingly popular, and some of the earlier models are inexpensive. Polarised dermoscopes, such as the DermLite range of instruments (3Gen, LLC [San Juan Capistrano, Calif, USA]), offer the advantages of creating less mess (immersion fluid is not required) and better resolution of vascular structures. However, certain features critical for diagnosis of melanoma may be harder to appreciate with polarised systems (eg, the presence of regression structures or blue–white veil).2 The use of dermoscopy is fairly mainstream among dermatologists in continental Europe (Giuseppe Argenziano, Assistant Professor, Department of Dermatology, Second University of Naples, personal communication), where the technology was first established in the 1980s. However, dermatologists in the United States have been slow to embrace the technology: only 17% of dermatologists surveyed in a 2001 study were using the tool.3 In our personal experience, there is an increasing demand from Australian GPs for dermoscopic educational seminars. Given the high incidence of skin cancer in Australia, and the important role that Australian GPs play in managing the disease, we support Menzies’ assertion that training and familiarity with dermoscopy should be a priority.1 Survey of use and value of dermoscopy among Australian general practitioners and dermatologists GPs (n = 223) Dermatologists (n = 179) Never use dermoscopy 66% 5% Favoured instrument Welch Allyn EpiScope (41%) Heine Delta 20 Dermatoscope (32%) Use computer-assisted dermoscopy 5% 3% Claim that dermoscopy influences diagnosis 75% 97%

Alex J Chamberlain MB BS(Hons), FACD · John W Kelly MD, FACD

To the editor: Bairnsdale ulcer is known by the eponyms Buruli in Uganda, Kakerifu in Zaire, Kumusi in New Guinea, and was formerly referred to as Searls’ ulcer in Australia. In the original 1948 article describing the causative organism,1 MacCallum and colleagues acknowledged assistance from Drs Alsop, Clay and Searls, in that (alphabetical) order. In sending material to Melbourne for examination, these doctors of the Bairnsdale Clinic described the ulcers, and also commented on the similarity of their appearance in the first three patients. J R Searls, after whom the ulcer was originally named, was regarded as an excellent general practitioner. He died in 1971.

Derek H Meyers

“What’s in a name? That which we call a rose By any other name would smell as sweet.” — William Shakespeare, Romeo and Juliet; II, ii, 1-2; circa 1595 Comment: In 1948, MacCallum and colleagues published an article reporting a new mycobacterial infection in man,1 and later named the causative organism Mycobacterium ulcerans. In their article, they described six patients, five of whom came from the Bairnsdale district in Gippsland, Victoria. Three Bairnsdale general practitioners, Drs Alsop, Clay and Searls, had initially recognised a novel disease in their region and submitted pathological specimens to Melbourne University for diagnosis.2 Subsequently, the same disease was described in many different areas, mostly in Africa (“Buruli ulcer”). Each new outbreak tended to give rise to a new name; of all these, perhaps the most colourful is “Sik belong Sepik”, describing the infection as it occurs along the Sepik River in Papua New Guinea. In Victoria, where most Australian cases of M. ulcerans infection occur,3 we have continued to use the term “Bairnsdale ulcer” even though the main endemic areas are now the Bellarine and Mornington Peninsulas near Melbourne.3 Medical eponyms have a place for diseases that are poorly understood or have unknown causes, but it could be argued that the terms “Bairnsdale ulcer” and “Buruli ulcer” now belong in the annals of medical history. However, there are other considerations. In 1998, the World Health Organization launched the Global Buruli Ulcer Initiative.4 This successful advocacy raised the profile of this neglected disease and facilitated major improvements in diagnosis and treatment. For better or worse, “Buruli ulcer” has become the internationally recognised term for M. ulcerans infection, and we propose that we should now also adopt this name in Australia. While this should come as a relief to the good citizens of Bairnsdale and the Bellarine peninsula, what about those of Buruli in Uganda? Fortunately, their county has been renamed and is now known as the Nakasongola District.5

Paul D R Johnson · John A Hayman