Dermatology

CorrectionIncorrect text: In “Frequency of sunburn in Queensland adults: still a burning issue” published in the 6 May 2013 issue of the Journal (Med J Aust 2013; 198: 431-434), the third sentence on page 431 should read: “In Australia, skin cancers cost more than other major cancers.2”

Adèle C Green · Louise Marquart · Susan L Clemens · Catherine M Harper · Peter K O'Rourke

Objective: To assess the current frequency of sunburn, a preventable risk factor for skin cancer, among Queensland adults.Design and setting: Cross-sectional population-based surveys of 16 473 residents aged ≥ 18 years across Queensland in 2009 and 2010.Main outcome measures: Proportion of the adult population reporting sunburn (skin reddening lasting 12 hours or more) during the previous weekend, by age, sex and other risk factors.Results: ...

Adèle C Green MB BS, PhD, FAAPHM · Louise Marquart BSc, BEcon, BAppSc(Hons) · Susan L Clemens BA, MPH · Catherine M Harper BSc, MPH · Peter K O’Rourke BSc(Hons), BA(Hons), PhD

Non-melanoma skin cancer treatments increased by 86% between 1997 and 2010. The authors anticipate that the number and the total cost without inflation of non-melanoma skin cancer treatments will increase by a further 22% between 2010 and 2015.

Marloes Fransen MB BS · Amalia Karahalios BSc, MPH · Niyati Sharma MB BS · Dallas R English BSc, MSc, PhD · Graham G Giles BSc, MSc, PhD · Rodney D Sinclair MB BS, MD, FACD

To the Editor: Hyperhidrosis is uncontrollable, excessive sweating. Severe primary focal palmar hyperhidrosis is a significant disability. It interferes with many activities of daily living and induces social avoidance behaviours that can lead to symptoms of social anxiety disorder. Symptoms begin in childhood or around puberty and affect both sexes equally.1 There are a number of treatments for palmar hyperhidrosis, which have varying degrees of success. ...

Ingrid C Chung · Bruce C L McGeorge

To the Editor: A 24-year-old Sudanese woman presented to her general practitioner in 2011 with one month of fatigue, dizziness, abdominal distension and facial oedema. Hypocortisolaemia was present: morning cortisol, 13 nmol/L (reference interval [RI], 240–620 nmol/L), afternoon cortisol, 9 nmol/L (RI, 100–280 nmol/L). In contrast to this profile, she appeared cushingoid (moon facies, central obesity, skin fragility and striae) with skin depigmentation on her face, back and hands (Box, A). ...

Rebecca F Goldstein · Helena J Teede · Carolyn A Allan

To the Editor: A 12-year-old boy presented to a regional emergency department with a 3-day history of progressing bilateral conjunctival injection, fevers (39°C), a widespread erythematous bullous rash, and superficial erosions to his lips, oral mucosa and urethral meatus. The patient was admitted to hospital for management of Stevens–Johnson syndrome (SJS). Initial treatment included intravenous f luids, intravenous ceftriaxone and oral azithromycin before transfer to a tertiary referral hospital. The patient had not taken any oral medications or over-the-counter therapies. He had no preceding viral symptoms. However, 2 weeks before onset of symptoms, he had received vaccination against varicella-zoster virus. On Day 1 of admission, intravenous immunoglobulin (Intragam P, CSL, Melbourne, VIC; batch numbers 3740600696, 3740500668, 3740600690, 3740600679) was administered at a dose of 1 mg/kg and repeated 20 hours later. On Day 2, oral prednisolone therapy (1 mg/kg/day) was initiated and continued for 5 days, and antibiotics were administered for 8 days (cefotaxime [50 mg/kg] and azithromycin [10 mg/kg]). Mycoplasma pneumoniae serological testing of blood samples taken on admission was negative. Bilateral conjunctival ulcers were managed with topical chloramphenicol eye ointment, topical 0.5% prednisone, lubricant drops and normal saline washes. The patient developed further areas of bullae and erosions to his cheeks and ears (Box). He also developed palmar papules, and dusky finger tips and toes. Skin bullous lesions were managed with daily sterile aspiration, and erosions were managed with silver-impregnated silicone dressings (Mepilex Ag, Mölnlycke Health Care, Gothenburg, Sweden). The patient’s rash and fevers abated, and he was discharged on Day 12 with advice from the dietitian and physiotherapy-assisted mobilisation. Sequelae at 2 months included cutaneous post-inflammatory hyperpigmentation. SJS after varicella infection has been reported,1,2 and a single case after varicella vaccination was included in a case series of six possible cases of SJS after vaccinations.3 SJS after medication use or infection with M. pneumoniae is well documented; however, cases where no clear cause can be documented result in increased parental anxiety. This case of SJS was preceded by varicella-zoster vaccination performed as part of school protocol. In the absence of any other obvious cause, it has been reported to alert practitioners of the possibility of a link (Therapeutic Goods Administration adverse drug reaction no. 291111). Patient with Stevens–Johnson syndrome after varicella vaccination

Elizabeth M Christou · Orli Wargon

A 36-year-old Chinese man had been born with multiple coloured lesions on his face, sclera, neck, trunk and limbs. Physical examination revealed extensive capillary malformations (naevus flammeus or port wine stain) on his neck, chest, back and upper limbs (Figure, A). Bluish-grey macules involved the left V2 dermatomal distributions of his face and conjunctiva, consistent with naevus of Ota and melanosis oculi (Figure, A). Aberrant Mongolian spots were present on his trunk (Figure, B and C). No other positive findings were noted. A diagnosis of phacomatosis pigmentovascularis (phacomatosis cesioflammea form) was made. Phacomatosis pigmentovascularis is defined as the coexistence of an extensive vascular naevus and various melanocytic lesions.1 It is estimated that 50% of patients with phacomatosis pigmentovascularis have systemic involvement, particularly of the eyes and central nervous system.1,2 No systemic involvement was evident in this patient.

Jianjun Qiao · Hong Fang

A 60-year-old woman with a history of severe depression presented with erysipelas of the lower limbs. Her feet were malodorous, with thickened skin, a leathery texture, hyperkeratosis and fissuring. Severe onychogryphosis was also observed (Box). She lived in a country house with her son, who was developmentally delayed, in conditions of poor hygiene, and refused any outside assistance. Onychogryphosis (also known as “ram’s horn nails”) may be associated with several factors, including peripheral vascular disorders, infection, injury, diabetes, or the inadequate intake of nutrients, but most often, as in this case, it occurs as a result of long-term neglect. Severe onychogryphosis, with thickened, curved, discoloured toenails penetrating adjacent toes

Nicola Mumoli

To the Editor: The Australian state of Queensland has one of the highest rates of melanoma and non-melanoma skin cancer in the world.1,2 Solar ultraviolet (UV) radiation is the most important environmental risk factor,3 highlighting the need for sun safety education and skin cancer screening among outdoor workers in Queensland. Many such programs are currently in place, including the Sunsafe Workplace Program developed by the University of Queensland in collaboration with the Queensland Skin and Cancer Foundation in 2007. In August 2010, we attended an outdoor workplace in Brisbane, with extensive sun safety policies already in place, to perform free voluntary skin checks on employees. Of 55 people invited to participate, 39 accepted. Of these, 36 were male, the median age was 35 years (range, 19–62 years), and 28 were of British and/or Irish ancestry. Eighteen participants reported spending 5–8 hours a day outdoors mid week and 20 reported the same at weekends. Six reported that at the start of summer, they never tanned and always burned, and 31 reported burning first, then tanning. Nearly half reported having had more than five painful sunburns in their lifetime. Despite these results, only a third of participants (13) reported wearing sunscreen, less than half (17) reported wearing a hat, and two-thirds (26) reported wearing sunglasses more than 50% of the time. Of the 39 participants, we referred one to his general practitioner for management of two non-melanoma skin cancers. About half of the participants reported having had formal skin checks before. Of these, one had previously had melanoma and five had non-melanoma skin cancers, and 10 had one or more suspicious naevi removed in their lifetimes. The main reasons given for not having had a previous skin examination were fear of skin cancer diagnosis and difficulty attending appointments during working hours. We found that providing easy access to free on-site skin examinations reduced interference to the work day, made appointments more accessible (both physically and financially), and enabled us to provide personalised information about participants’ skin and skin cancer risks and reassure those who had been anxious about receiving skin cancer diagnoses. We found that workers were relieved when told they had nothing suspicious presenting on the day, and that they seemed less anxious about seeking skin checks in the future. Despite many public awareness campaigns on skin cancer and the establishment of sun safety programs in the workplace, we found there is still room for improvement. Although clinical guidelines do not currently recommend routine skin cancer screening for the general population,4 the success of our visit leads us to encourage workplaces that are exposed to solar UV radiation to consider providing on-site skin examinations for employees, as well as ongoing sun safety education. We believe such services can help to break down barriers that prevent people from seeking medical assessment and management, and can help to spread the safety-in-the-sun message.

Nicola C Douglas · Laura Baillie · H Peter Soyer

To the Editor: A 44-year-old female nurse with a 4-year history of hand dermatitis was referred to an occupational dermatology clinic in Melbourne. In 2009, her hand dermatitis had worsened when she started working in a neonatal intensive care unit, where she used antimicrobial hand gel more frequently. Her hands improved when she spent time away from work but worsened again within 2 days of returning. Patch testing was conducted using our baseline patch test series as well as rubber accelerators (used in manufacturing rubber gloves), antiseptics and the patient’s own samples (eg, gloves, moisturiser, etc). She developed positive reactions to formaldehyde and the formaldehyde releasers quaternium 15, imidazolidinyl urea and diazolidinyl urea, as well as the hand gel she had been using — Microshield Antimicrobial Hand Gel (Johnson and Johnson Medical, Sydney, NSW) — a gel containing 30%–60% water, and diazolidinyl urea as a preservative. (Diazolidinyl urea is not listed on the safety data sheet for this product as it is in a concentration of < 1%.) A negative result for a radioallergosorbent test indicated it was unlikely the patient was allergic to latex. She was advised to use a waterless, alcohol-based hand cleaner without preservatives and was given advice about general skin care, especially use of moisturising cream.1 She complied with this advice, and her condition subsequently improved. Diazolidinyl urea is a preservative commonly used in cosmetic products. Once absorbed into the skin, it releases small amounts of formaldehyde. Individuals may become sensitised to diazolidinyl urea, formaldehyde, or both. This can occur at any stage, even if the individual has been exposed to the product for years. At our occupational dermatology clinic we have patch tested 2688 patients and diagnosed 1461 of these with allergic contact dermatitis (ACD) over the past 16 years. Nine health care workers have been diagnosed with ACD to diazolidinyl urea contained in products they used at work. Thirty other patients have had ACD caused by this preservative from other sources, usually their skin care products. Many workers will simply accept their hand dermatitis as part of the job, or begin treatment without patch testing. It is only with patch testing that an accurate diagnosis can be made. Waterless hand cleaners are an important part of hand hygiene in health care settings,2 and they minimise irritation caused by washing hands with soap and water and drying with paper towels.3 Alcohol-based liquid hand-disinfectant solutions are more efficacious than gels.4 Our report provides another reason to use these products as, generally, alcohol-based liquids do not contain preservatives such as diazolidinyl urea.

Jennifer L Cahill · Rosemary L Nixon

Clinical record A 22-year-old woman of European ancestry who had a 4-year history of treatment-resistant bipolar disorder presented with symptoms of mania. On admission to hospital, a full blood examination and biochemistry results were normal. Her current doses of lithium (1500 mg daily) and risperidone (2 mg daily) were maintained while treatment with carbamazepine was commenced at 100 mg daily and then increased by 100 mg every 3 days. The patient was discharged from hospital on a regimen of 400 mg carbamazepine daily. Her plasma carbamazepine level at this time was 19 μmol/L (reference range [RR], 16–50 μmol/L). She was in good physical health, and a full blood examination and biochemistry results were normal. Three weeks after starting to take carbamazepine, the patient developed a mild, barely visible, erythematous maculopapular rash on her arms and chest that disappeared after a few days. She had no other symptoms, and full blood examination and biochemistry results remained normal. After a further 3 weeks, the patient developed marked lethargy, exercise intolerance, muscle aches, night sweats, rigors and a rash. There had been no changes to her medication and she had been complying with her treatment regimen. She lived with her family, and her parents contacted her family general practitioner as well as me (her psychiatrist). She was advised to stop taking carbamazepine, increase the dose of risperidone and seek urgent medical attention. The carbamazepine was stopped over 2 days — 45 days after it was first administered. The family consulted an emergency service on four occasions over 6 days, and the patient was variously diagnosed with contact dermatitis, non-specific allergic reaction, cytomegalovirus and rubella. She was finally admitted to hospital and was found to be febrile (temperature, 38–40º C) and tachycardic (heart rate, 108 beats per minute), with an intensely pruritic maculopapular rash that had spread over most of her body. Her face was swollen, showing periorbital oedema. There was no mucosal involvement or epidermolysis. She had occipital, supraclavicular and inguinal lymphadenopathy, and hepatosplenomegaly. Liver function test results were markedly abnormal (alanine aminotransferase [ALT], 1203 IU/L [RR, < 41 IU/L]; alkaline phosphatase, 156 IU/L [RR, 30–120 IU/L]) and her serum albumin level was low (29 g/L [RR, 35–50 g/L]. She had lymphocytosis (lymphocyte count, 5.9 × 109/L [RR, 1.0–4.0 × 109/L), but her C-reactive protein level was not raised. A diagnosis of anticonvulsant hypersensitivity syndrome was made. The patient was transferred to the intensive care unit, where she remained for 48 hours, and treatment with prednisolone 40 mg daily was commenced. Her physical state improved rapidly. After 7 days her ALT level had dropped to < 500 IU/L and she was deemed well enough to be discharged. The prednisolone was gradually tapered by 5 mg per week. Topical betamethasone helped to soothe her pruritus and inflammation, and some mild exfoliation occurred. The patient continued to improve over the next 6 weeks. Her rash disappeared, as did her hepatosplenomegaly, and liver function test results normalised. She recovered fully and has remained on lithium and risperidone. Anticonvulsants are being used increasingly for mood disorders and chronic pain. Anticonvulsant hypersensitivity syndrome (ACHS) has been reported to occur with use of phenytoin, carbamazepine, phenobarbitone and lamotrigine, but not valproate. It is a rare and potentially fatal complication. ACHS is indicated by the presence of a triad of characteristic clinical features — fever, rash and internal organ involvement. It is estimated to occur in about 1 in 1000 to 1 in 10 000 patients who are exposed to these anticonvulsants.1 A similar reaction has also been described with exposure to sulfonamides, sulfones, allopurinol and non-steroidal anti-inflammatory drugs (piroxicam in particular).2 This reaction has also been referred to as drug-related rash with eosinophilia and systemic symptoms (DRESS) syndrome, and drug-induced hypersensitivity syndrome (DIHS).3 This patient showed a pattern of symptoms quite typical of ACHS, which usually appears after a brief delay of 2–4 weeks after anticonvulsant exposure, but may appear up to 12 weeks later.1 Her symptoms began to emerge about 6 weeks after she commenced taking carbamazepine, although a mild rash appeared after 3 weeks. Transient rashes are quite common following initiation of carbamazepine therapy and are not an indication for stopping the drug. Clinicians often fail to consider a diagnosis of ACHS.4 Although the seriousness of the illness was initially not obvious, it was fortunate that administration of carbamazepine had been stopped as soon as significant symptoms began to emerge. It is noteworthy that the patient’s physical state continued to deteriorate following withdrawal of carbamazepine, and only improved 1 week later, after hospital admission and treatment with prednisolone. Her mental state did not worsen during her acute illness, and she showed great resilience. Prednisolone has potent mood-altering properties and presents a significant risk for inducing either depression or mood elevation. Close monitoring of mental state and psychiatric involvement is recommended. Carbamazepine has been linked with a variety of hypersensitivity reactions, ranging from mild and benign urticaria and erythematous maculopapular eruptions to Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). ACHS is usually not as serious as SJS or TEN but can be life-threatening, and deaths from it have been reported.5 The skin condition can be extensive in ACHS, but is not as severe as the detachment of body surface area seen with SJS or TEN, which often involves gastrointestinal or tracheobronchial epidermal surfaces. Lessons from practice Anticonvulsant hypersensitivity syndrome (ACHS) is a rare and potentially fatal complication of treatment with the anticonvulsants phenytoin, carbamazepine, phenobarbitone and lamotrigine. Diagnosis is clinical and based on a triad of features: fever, rash and internal organ involvement. Early suspicion of diagnosis is essential, as the critical component of treatment is cessation of the implicated drug. Pharmacogenetic testing for the human leukocyte antigen allele B*1502 should be considered before commencing carbamazepine in patients of Asian ancestry. Genetic factors predispose individuals towards the development of these reactions, and recent data have linked human leukocyte antigen allele B*1502 as a marker in Asian populations, except among people of Korean and Japanese ancestry. Genotyping is recommended for at-risk groups;6 the prevalence of the allele is negligible in other ethnic groups.6 ACHS is associated with complex immunological changes that include chemotoxic and T-cell-mediated inflammatory injuries to tissues containing cytochrome oxidases.2 Viral infection may increase an individual’s vulnerability.7 The most critical component of management of ACHS is discontinuation of the implicated drug.1 All clinicians who prescribe anticonvulsant drugs therefore need to be aware of ACHS and the requirement for early suspicion of the diagnosis. General supportive measures and systemic corticosteroids are usually given, which in most instances results in full recovery. There is cross-sensitivity among aromatic anticonvulsant drugs (phenytoin, carbamazepine, phenobarbitone and lamotrigine), which means that patients who have had ACHS should avoid all of these drugs.4 In addition, a familial association with ACHS exists, and family members of these patients need to be informed that they may be at increased risk of developing this syndrome. Anticonvulsant drugs that are generally considered safe are valproate and benzodiazepines.4

Isaac Schweitzer MD, DPM, FRANZCP

Objective: To examine the feasibility of balancing sunlight exposure to meet vitamin D requirements with sun protection guidelines.Design and setting: We used standard erythemal dose and Ultraviolet Index (UVI) data for 1 June 1996 to 30 December 2005 for seven Australian cities to estimate duration of sun exposure required for fair-skinned individuals to synthesise 1000 IU (25 μg) of vitamin D, with 11% and 17% body exposure, for each season and hour of the day. Periods were classified according to whether the UVI was < 3 or ≥ 3 (when sun protection measures are recommended), and whether required duration of exposure was ≤ 30 min, 31–60 min, or > 60 min.Main outcome measure: Duration of sunlight exposure required to achieve 1000 IU of vitamin D synthesis.Results: Duration of sunlight exposure required to synthesise 1000 IU of vitamin D varied by time of day, season and city. Although peak UVI periods are typically promoted as between 10 am and 3 pm, UVI was often ≥ 3 before 10 am or after 3 pm. When the UVI was < 3, there were few opportunities to synthesise 1000 IU of vitamin D within 30 min, with either 11% or 17% body exposure.Conclusion: There is a delicate line between balancing the beneficial effects of sunlight exposure while avoiding its damaging effects. Physiological and geographical factors may reduce vitamin D synthesis, and supplementation may be necessary to achieve adequate vitamin D status for individuals at risk of deficiency.

Kellie L Stalgis-Bilinski BSc, MNutrDiet, APD · John Boyages MB BS(Hons), FRACR, PhD · Elizabeth L Salisbury MB BS(Hons), FRCPA, FFOP · Colin R Dunstan PhD(Med), MSc, BSc(Hons) · Stuart I Henderson BSc, PhD(Applied Physics) · Peter L Talbot BSc, PostgradDipNutrDiet, MSc

A 20-year-old man presented with a well defined, brown, mildly erythematous, reticulated patch lesion on his left thigh (Figure). Although livedo reticularis could be suggested, the clinical presentation was in keeping with erythema ab igne. On questioning, the patient described the frequent use of a laptop on his thighs, with the heat source on the left side. Erythema ab igne can be precipitated by any heat source (eg, hot water bottles, heating pads). We recommended that he cease using the laptop directly on his lap or place the laptop on a hard surface. Clinicians should be aware of this condition to avoid unnecessary medical examinations, and users of laptops should be advised about the effect of heat on their skin. [[{"type":"media","view_mode":"media_large","fid":"39839","attributes":{"alt":"","class":"media-image","typeof":"foaf:Image"}}]]

Niranthari Chinniah · Pablo Fernández-Peñas

A 19-year-old Sudanese woman, who had lived for about a decade in Ugandan refugee camps, was referred for investigation of a 12-month history of a generalised rash. Two months later, her condition had deteriorated to include cachexia and drowsiness. Despite initial negative findings on investigation, human African trypanosomiasis (HAT) was suspected, and parasites were found in a double-centrifuged sample of cerebrospinal fluid. Eflornithine, the appropriate drug for treatment of late-stage disease, was obtained through the World Health Organization. This case highlights the diagnostic and therapeutic difficulties in managing late-stage HAT in a non-endemic country. Clinical recordIn January 2008, a 19-year-old Sudanese woman was referred from the community to a tertiary hospital for investigation of a 12-month history of generalised pruritus. There were no obvious precipitants or triggers for the itch. She was born in southern Sudan, but had lived in refugee camps in north-western Uganda for about a decade before migrating to Australia in November 2006. Her past medical history was non-contributory. Initial examination showed generalised hyperpigmented papules and nodules with excoriations. Prurigo was diagnosed, and treatment with topical corticosteroids was trialled. By March 2008, her condition had deteriorated, and she experienced lethargy, apathy, fevers, night sweats, weight loss, reduced rousability, abulia (impairment or loss of willpower) and seizures. The pruritus was pervasive and the scratching automatic. A past family history of human African trypanosomiasis (HAT) in her mother, which was diagnosed and treated in Uganda, was elicited. On examination, she had cachexia, and was drowsy, but rousable, and oriented to person, but not place or time. She had generalised itch with hyperpigmented, lichenified papules and excoriated nodules (Figure 1). Neurological examination showed symmetrical brisk reflexes, bilateral upper-limb cogwheeling, and myoclonic jerks involving her limbs, mouth and periocular muscles. She had palpable posterior cervical lymph nodes of less than 1 cm in diameter. Late-stage HAT was suspected, and she was admitted to hospital for further investigation. Differential diagnoses included other infective encephalitides (tuberculous and viral), vascular events and malignancies (lymphoma). Investigations showed that the patient had microcytic anaemia (haemoglobin concentration, 96 g/L; reference range [RR], 115–145 g/L), which was attributed to a known α-thalassemia trait: her renal function and hepatic function were normal. Her erythrocyte sedimentation rate was 42 mm/h (RR, < 20 mm/h). Elevated concentrations of total serum protein (104 g/L; RR, 60–80 g/L), gammaglobulin (32 g/L; RR, 8–16 g/L), IgG (24.3 g/L; RR, 5.8–13.7 g/L) and IgM (7.8 g/L; RR, 0.3–1.7 g/L) were detected. A skin biopsy suggested lichen simplex chronicus. Initial peripheral blood smears, lymph node and bone marrow aspirates all tested negative for parasites. Examination of the cerebrospinal fluid (CSF) revealed a mononuclear pleocytosis of 100 × 106 cells/L (RR, < 5 × 106 cells/L), an elevated protein level (0.9 g/L; RR, 0.15–0.45 g/L), markedly elevated level of IgM (0.36 g/L; RR, undetectable) and a low level of glucose (2.1 mmol/L; RR, 2.4–4.6 mmol/L); micro-organisms were not seen on examination of the centrifuged deposit. Gadolinium-enhanced magnetic resonance imaging (MRI) showed bilateral, symmetrical, widespread high-signal white matter change on T2-weighted imaging (Figure 2). Simultaneous T2-weighted images demonstrated high signal changes in the splenium, the brainstem and the cerebellar white matter (images not shown), and post-gadolinium images showed minimal leptomeningeal enhancement (images not shown). An electroencephalogram (EEG) showed diffuse delta-wave slowing consistent with a metabolic encephalopathy, with no evidence of ictal activity. Despite initial negative results on CSF testing, HAT was suspected on clinical grounds. Thus, repeat large-volume CSF examination was performed. Direct examination of CSF was again negative, but double-centrifuged CSF microscopy showed trypanomastigotes (Figure 3), confirming the diagnosis of late-stage HAT. Both subspecies of Trypanosoma brucei can be acquired in Uganda.1 We considered Trypanosoma brucei gambiense infection to be more likely in this patient as it is hyper-endemic in north-western Uganda and because of the subacute clinical presentation. However, as Trypanosoma brucei rhodesiense infection remained plausible, given the patient’s past travel to southern Uganda, subspecies testing was indicated. Lacking an Australian medical reference laboratory for this, we referred specimens to the Institute of Tropical Medicine (Antwerp, Belgium) for serological testing, and to a local reference laboratory for nucleic acid amplification testing.2 While awaiting results, the patient became uncommunicative, bed-bound and increasingly cachectic, making empiric trypanocidal therapy imperative. Treatment for late stage T. b. gambiense infection was commenced 19 days after admission, with intravenous eflornithine (obtained through the World Health Organization [WHO]) at a dose of 100 mg/kg every 6 hours for 2 weeks. This was tolerated without significant toxicity. At discharge on Day 39, the patient was orientated, communicative and walking independently despite persistence of slight limb hypertonia. Subsequently, subspecies serology showed elevated titres to T. b. gambiense on a serum immunofluorescent antibody test (IFAT; titre, 1:1600; RR, negative) and a card agglutination antibody test (CAAT; titre, 1:32; RR, negative). The CSF IFAT titre to T. b. gambiense was 1: 8 (RR, negative). The local nucleic acid amplification test suggested T. b. rhodesiense (data not shown), but this was felt to be clinically discordant. Three months after discharge, the patient was lucid, conversant in both English and her native tongue, neurologically intact and free from itch. Examination of her CSF showed improving pleocytosis with normal biochemical findings. MRI verified improvement; the post-contrast enhancement had resolved, but mild, diffuse cerebral atrophy was evident. She has resumed her studies and normal social activities and was relapse free at 16-month follow-up. DiscussionHuman African trypanosomiasis or sleeping sickness is caused by two subspecies of the haemoflagellate parasite Trypanosoma brucei — T. b. rhodesiense (east-African HAT) and T. b. gambiense (west-African HAT).1,3 The parasite is transmitted by the bite of tsetse flies (Glossina spp.).1 HAT is endemic only in sub-Saharan Africa, where the WHO estimates that between 300 000–500 000 people are currently infected, with 100 000 deaths directly attributed to this disease annually.3 Uganda is currently the only country where infection with both subspecies occurs. While the two foci of trypanosomiasis within Uganda appear separate, as a result of civil unrest, population displacement and the northward spread of wild and domestic animals from central and south-east Uganda, it is likely that these foci will soon converge.4-6 HAT is rarely diagnosed outside Africa. When T. b. gambiense infection is diagnosed, it is usually in the late (secondary) stage.1,7 To our knowledge, this is the first case of T. b. gambiense infection diagnosed in Australia. HAT is a biphasic disease. Early-stage disease (Stage I) denotes the post-inoculation period followed by haemo-lymphatic spread.1 An inflammatory nodule or ulcer (chancriform) may be seen at the site of inoculation, more commonly with T. b. rhodesiense infection.1 Lymphatic spread results in lymphadenopathy, with posterior cervical lymphadenopathy (Winterbottom’s sign) typical in T. b. gambiense disease.1,3 Haematogenous spread produces fluctuating fevers, hepatosplenomegaly, serositis and myocarditis, which occur in both forms of the infection, but are more common in T. b. rhodesiense disease.1 In late-stage disease (Stage II), the parasite passes through the blood–brain barrier into the central nervous system, resulting in meningoencephalitis, which is invariably fatal if not treated.1,3 Headache, ataxia, itching, speech disturbance, behavioural change, extrapyramidal signs and mental state changes may manifest.1,3 Pineal and thalamic invasion leads to hypersomnolence and circadian rhythm disruption.3 The natural history of the diseases caused by the two subspecies varies significantly; T. b. gambiense infection is insidious (over months to years), whereas T. b. rhodesiense infection usually progresses over days to weeks.1 Dermatological manifestations of HAT are non-specific. Pruritus is a pervasive symptom, present in over 50% of cases, and is a feature of disease chronicity.8 Pruritus generally correlates with greater CSF pleocytosis.8 Parasternal and generalised pruritus are common, as is peripheral oedema. Transient urticarial and macular eruptions have also been described.1,9 In very chronic disease (of more than 24 months’ duration), pruritus may decrease, heralding a pre-terminal phase of illness.8 Definitive diagnosis of HAT requires direct visualisation of the parasites in blood, CSF or tissue. Detection of trypanosomes in the CSF confirms late-stage disease. False negative results are common because of the low number of parasites in T. b. gambiense infection.1 As in the case we present here, concentration techniques such as double-centrifugation of CSF increase the sensitivity of microscopy.10 Non-diagnostic CSF changes include: lymphocyte counts of > 5/μL, increased CSF protein and IgM concentrations, and morula (Mott) cells.9,11 Identifying the subspecies of trypanosomes is difficult because both subspecies are morphologically identical. The serological tests CAAT and IFAT are available for the detection of T. b. gambiense antibodies, and this is useful in screening high-prevalence populations.9 The use of nucleic acid tests for the subspeciation of T. b. rhodesiense and T. b. gambiense is an emerging technique, and has been used successfully in the research setting.5,6,9 However, these assays are not widely available.9 Obtaining a detailed travel history from patients and recording the timing of symptoms and signs over the course of the illness remain important for differentiating the two forms of the disease. Treatment of HAT depends on the subspecies of infecting trypanosome and disease stage. Patients with early-stage disease should have CSF examination to exclude subclinical neurological involvement.9 In Australia, treatment is challenging because we have limited access to targeted therapies for HAT. The necessary drugs are accessible through the WHO. Treatments for early-stage HAT infections are parenteral pentamidine for T. b. gambiense disease and suramin for T. b. rhodesiense disease.1,6 For late-stage HAT, melarsoprol was formerly the treatment of choice.1 However, 3%–10% of patients treated with melarsoprol develop encephalopathy, which is fatal in 10%–70% of cases. Survivors of encephalopathy frequently have residual brain damage.12,13 Eflornithine is equally efficacious and less toxic than melarsoprol12,13 for late-stage T. b. gambiense infection, with lower treatment-related mortality (about 0.8%).13 Adverse effects of eflornithine include seizures, gastrointestinal upset and neutropenia, but treatment interruption is generally not required.1 Recently, one week of combination therapy with nifurtimox and eflornithine was shown to be equally effective, less toxic and easier to administer than eflornithine monotherapy for late-stage T. b. gambiense infection,14 and is now considered the treatment of choice for this infection.15 Recommended follow-up after treatment for late-stage HAT includes 3–6-monthly CSF examinations for 2 years.4 This case highlights the diagnostic and therapeutic difficulties in managing late-stage HAT in a non-endemic country. Clinicians need to be aware of infections that are non-endemic to Australia that can occur in recently arrived travellers and migrants. Appropriate treatment of HAT is life-saving and associated with good clinical outcomes. Figure 1 The patient’s rash on presentation in March 2008, showing hyperpigmented, lichenified papules and nodules with excoriation involving the trunk. Figure 2 Axial T2-weighted magnetic resonance image showing high signal in both basal ganglia (white arrow) and symmetrical high signal in the white matter, including the internal and external capsules (black arrows). Figure 3 Double centrifuged sample of the patient’s cerebrospinal fluid shown on direct microscopy showing a trypanomastigote typical of Trypanosoma brucei, the pathogen of human African trypanosomiasis (Giemsa stain; original magnification, × 800).

Paul Cherian MB BS · Ralph K Junckerstorff MB BS · David Rosen MB BS, FRACP, PhD · Prasad Kumarasinghe MD, FACD · Alan Morling BSc · Philip Tuch MB ChB, FRACP · Sonja Raven MB ChB, FRANCR · Ronan J Murray MB BS, FRACP, FRCPA · Christopher H Heath MB BS, FRACP, FRCPA

To the Editor: A 69-year-old Indigenous Australian man, with no known Caucasian ancestry, presented in 2008 with a 7-week history of depigmentation of the face and neck, which was initially intensely pruritic and erythematous. He had neither a personal history nor family history of vitiligo, but a 2 mm thick, Clark level III, superficially spreading melanoma had been widely excised from his right lateral calf in 2001; results of a right inguinal sentinel node biopsy had been negative. In 2005, multiple small local recurrences on the right lower leg had been surgically removed. Two years later, further histologically confirmed local cutaneous and subcutaneous recurrences were excised, but new lesions continued to develop. His medical history included type 2 diabetes mellitus, hypertension, atrial fibrillation and coronary artery bypass grafting. He had no family history of melanoma. The onset of facial inflammation and depigmentation over a few days in 2008 was associated with complete regression of some leg lesions and partial regression of others. The facial inflammation settled spontaneously within a week. Computed tomography of the abdomen and pelvis at this time did not show any distant disease. The patient was unconcerned by the depigmentation and declined treatment. Over the following 5 months, the extent of his head and neck depigmentation increased (Box, A) and he developed more melanomas on his right lower leg, including one with a depigmented rim (Box, B). Positron emission tomography identified several areas of focally increased metabolism corresponding to the right lower leg lesions, but no evidence of disease elsewhere. The leg lesions have demonstrated only slow progression, and the patient continues to have 6-monthly follow-up at our department, as well as ongoing local review. Cutaneous melanoma is rare in Indigenous Australians, with only two reported cases of acral lesions.1,2 In melanoma, immunogenic factors may play a key role in disease course. Antibodies that cross-react with antigens on melanocytes and melanoma cells, such as tyrosinase, tyrosinase-related-protein-1 and tyrosinase-related-protein-2, can lead to both vitiligo-like autoimmune depigmentation and tumour regression.3 T-cell-mediated responses to melanoma antigens, such as MART-1 (melanoma antigen recognised by T-cells-1), are also enhanced in melanoma patients with depigmentation,3 which has been reported in approximately 3% of patients with stages III and IV melanoma.4 Vitiligo is a positive prognostic factor and has been reported in association with tumour regression distant from the depigmentation.4 In conclusion, this case of vitiligo-like depigmentation, affecting both the head and neck and a cutaneous metastasis, highlights the immune responsive potential of metastatic melanoma. Vitiligo-like depigmentation associated with melanoma in a 69-year-old Indigenous Australian man A: Extensive depigmentation of the face and neck 5 months after the onset of vitiligo. B: Depigmentation around the largest subcutaneous metastasis on the right lower leg.

Elizabeth M Christou · Diona L Damian · John F Thompson