Real-world effectiveness and safety of tofacitinib for alopecia areata: A retrospective cohort study of 202 patients.

BACKGROUND: Alopecia areata (AA) is an autoimmune hair loss disorder characterised by collapse of hair follicle immune privilege and mediated by autoreactive CD8+ T lymphocytes and natural killer cells. Treatment is often unsatisfactory. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is implicated in the pathogenesis of AA and Janus Kinase inhibitor (JAKi) medications are promising emerging treatments for AA. OBJECTIVES: We evaluated the safety and effectiveness of tofacitinib in a real-world setting over 18 months of treatment. METHODS: A retrospective cohort study of all patients with scalp AA commenced on tofacitinib between 1 November 2016 and 31 May 2019. The primary endpoint was the percent change in Severity of Alopecia Tool (SALT) score at 18 months. RESULTS: Two hundred and two patients were included. After 18 months of treatment, 55.9%, 42.6% and 29.2% achieved 50%, 75% and 90% reductions in their SALT scores respectively. Increased duration of AA was a negative predictor of hair regrowth. Males and patients with baseline SALT ≥90 were slower to respond to treatment in the first 12 months. One hundred and twenty-four patients and 168 patients received concomitant systemic corticosteroids or low-dose oral minoxidil during tofacitinib therapy respectively. There were no serious adverse events. CONCLUSION: Tofacitinib was a safe and effective treatment for patients with moderate-to-severe AA. Further randomised controlled studies are needed to establish the optimal treatment regimen.

Improving Skin cancer Management with ARTificial Intelligence (SMARTI): protocol for a preintervention/postintervention trial of an artificial intelligence system used as a diagnostic aid for skin cancer management in a specialist dermatology setting.

INTRODUCTION: Convolutional neural networks (CNNs) can diagnose skin cancers with impressive accuracy in experimental settings, however, their performance in the real-world clinical setting, including comparison to teledermatology services, has not been validated in prospective clinical studies. METHODS AND ANALYSIS: Participants will be recruited from dermatology clinics at the Alfred Hospital and Skin Health Institute, Melbourne. Skin lesions will be imaged using a proprietary dermoscopic camera. The artificial intelligence (AI) algorithm, a CNN developed by MoleMap Ltd and Monash eResearch, classifies lesions as benign, malignant or uncertain. This is a preintervention/postintervention study. In the preintervention period, treating doctors are blinded to AI lesion assessment. In the postintervention period, treating doctors review the AI lesion assessment in real time, and have the opportunity to then change their diagnosis and management. Any skin lesions of concern and at least two benign lesions will be selected for imaging. Each participant's lesions will be examined by a registrar, the treating consultant dermatologist and later by a teledermatologist. At the conclusion of the preintervention period, the safety of the AI algorithm will be evaluated in a primary analysis by measuring its sensitivity, specificity and agreement with histopathology where available, or the treating consultant dermatologists' classification. At trial completion, AI classifications will be compared with those of the teledermatologist, registrar, treating dermatologist and histopathology. The impact of the AI algorithm on diagnostic and management decisions will be evaluated by: (1) comparing the initial management decision of the registrar with their AI-assisted decision and (2) comparing the benign to malignant ratio (for lesions biopsied) between the preintervention and postintervention periods. ETHICS AND DISSEMINATION: Human Research Ethics Committee (HREC) approval received from the Alfred Hospital Ethics Committee on 14 February 2019 (HREC/48865/Alfred-2018). Findings from this study will be disseminated through peer-reviewed publications, non-peer reviewed media and conferences. TRIAL REGISTRATION NUMBER: NCT04040114.

Secondary organizing pneumonia (bronchiolitis obliterans with organizing pneumonia) associated with adalimumab for treatment of chronic plaque psoriasis.

Organizing pneumonia is defined histopathologically by intra-alveolar buds of granulation tissue, consisting of intermixed myofibroblasts and connective tissue. The pathological pattern of organizing pneumonia may be idiopathic or related to a determined cause, termed secondary organizing pneumonia. We report a 68-year-old woman with a longstanding history of chronic plaque psoriasis, treated with the tumor necrosis factor (TNF) inhibitor, adalimumab. After 8 years of treatment, she developed a gradual-onset, non-productive cough with associated generalized fatigue and mild dyspnea. Radiological investigations demonstrated ground-glass opacities in the left lower lobe and bronchoscopy revealed a fibroinflammatory process consistent with organizing pneumonia. Her biologic treatment was ceased and corticosteroid treatment commenced, with resolution of both her symptoms and the radiological findings. Given the increasing incidence of biologic treatment in the management of dermatological conditions, clinicians should be aware of secondary organizing pneumonia as a possible side effect of TNF inhibitor therapy.

Treatment of alopecia areata: An Australian expert consensus statement.

Alopecia areata (AA) severity varies from a single small patch to complete loss of scalp hair, body hair, eyelashes and eyebrows. While 40% of all affected individuals only ever get one patch and will achieve a spontaneous complete durable remission within 6 months, 27% will develop additional patches but still achieve complete durable remission within 12 months and 33% will develop chronic AA. Without systemic treatment, 55% of individuals with chronic AA will have persistent multifocal relapsing and remitting disease, 30% will ultimately develop alopecia totalis and 15% will develop alopecia universalis. The unpredictable course and psychological distress attributable to AA contributes to the illness associated with AA. Numerous topical, intralesional and systemic agents are currently used to treat AA; however, there is a paucity of data evaluating their use, effectiveness and tolerability. Topical therapy, including topical glucocorticosteroids, minoxidil and immunotherapy, can be used in cases of limited disease. There are no universally agreed indications for initiating systemic treatment for AA. Possible indications for systemic treatment include rapid hair loss, extensive disease (≥50% hair loss), chronic disease, severe distress or a combination of these factors. Currently available systemic treatments include glucocorticosteroids, methotrexate, ciclosporin, azathioprine, dapsone, mycophenolate mofetil, tacrolimus and sulfasalazine. The optimal treatment algorithm has not yet been described. The purpose of this consensus statement is to outline a treatment algorithm for AA, including the indications for systemic treatment, appropriate choice of systemic treatment, satisfactory outcome measures and when to discontinue successful or unsuccessful treatment.

Incidence and associations of painful neuroma in a contemporary cohort of lower-limb amputees.

BACKGROUND: The painful post amputation neuroma significantly impairs the prosthesis-wearing lower-limb amputee. It remains poorly understood, with literature limited to cohorts of traumatic amputees. This paper reports the incidence and associations of painful neuroma in a modern tertiary centre with a case load of amputations performed for both traumatic and non-traumatic indications. METHOD: This retrospective cohort study analysed the records of 304 patients who underwent all-cause lower-limb amputation at The Alfred Hospital between January 2002 and March 2012. Patients were included in our analysis if they completed 1-year follow-up at our Amputee Rehabilitation Clinic, producing a final cohort of 96 patients. In order to identify a painful neuroma post-operatively, both clinical suspicion, and either histopathological or radiological evidence were required. RESULTS: The overall incidence of symptomatic neuromas was 4.17%. There was no significant difference between patients who underwent amputation for a traumatic indication (6.25% (2/32) versus 3.13% (2/64); P = 0.59) compared to non-traumatic indication (P = 0.59). Visual analogue score at discharge and the presence of phantom limb pain at follow-up showed significant associations with the formation of painful neuroma. Dose of opioid on discharge, history of depression and current smoking did not reach statistical significance. CONCLUSION: This study presents a lower incidence of painful post-amputation neuroma to those published in the literature. This may be attributed to improved methodology. The described associations require further investigation into central factors leading to neuroma sensitization.

Epidemiology of skin cancer in the mature patient.

Epidermal cancers include keratinocyte cancer, melanocyte cancer, and Merkel cell carcinoma. These cancers account for the vast majority of new cancers diagnosed in Australia, North America, and Europe. Keratinocyte cancer is the most common epidermal cancer and accounts for 7 out of 8 new cancers diagnosed in Australia. Melanoma and Merkel cell carcinoma are less common than keratinocyte carcinoma but are more important causes of mortality in Australia. Keratinocyte cancer has also been demonstrated to be a marker of cancer-prone phenotype. Risk factors for epidermal cancer include intrinsic and environmental factors, in particular exposure to ultraviolet radiation and advanced age. Actinic keratosis has an approximate prevalence of 79% of men and 68% of women between 60 and 69 years of age, and has a low risk of malignant transformation into squamous cell carcinoma. Basal cell carcinoma is the most common malignancy in Caucasians worldwide, with the incidence increasing by 2% per year in Australia. Squamous cell carcinoma is the second most common epidermal cancer, with an incidence of approximately 1035 or 472 per 100,000 person-years in men and women, respectively. Primary risk factors for both basal cell carcinoma and squamous cell carcinoma include light skin color, UV radiation exposure, and chronic immunosuppression. Although the rate of melanoma is increasing, the mortality in Australia is reducing and is currently 9%. The overall incidence of melanoma in Australia is approximately 50 cases per 100,000 persons (62 for men and 40 for women). Keratinocyte carcinoma and melanoma are risk factors for developing further skin cancer and primary malignancy. This contribution reviews the incidence, prevalence, and risk factors associated with the development of epidermal cancer and premalignant epidermal neoplasia.

Common causes of paediatric alopecia

BACKGROUND: Hair loss in children aged 12 years and younger is most often due to a benign or self-limiting condition. This article presents a review of the assessment of common causes of paediatric alopecia and outlines the implications for general practice. OBJECTIVE: The objective of this article is to help readers systematically assess a child presenting with alopecia, manage the most common diseases of paediatric alopecia and identify patients requiring referral to a dermatologist. DISCUSSION: The most common causes of paediatric alopecia are largely non-scarring. These include tinea capitis, alopecia areata, trauma due to traction alopecia or trichotillomania, and telogen effluvium. Scarring alopecia can also occur in childhood and requires scalp biopsy and further investigation by a dermatologist. General practitioners should treat clear cases of tinea capitis. Referral to a dermatologist is necessary in cases when the diagnosis is uncertain, treatment is failing or there is evidence of scarring alopecia.

Optimising cryosurgery technique.

BACKGROUND: Cryosurgery is an effective, simple and inexpensive treatment used extensively in general practice and dermatology. It is used most commonly for actinic keratoses and warts; however, a large number of benign, premalignant and malignant skin diseases can also be treated. OBJECTIVE: The objective of this article is to help readers improve their cryosurgery technique. DISCUSSION: Application of the cryogenic agent (most commonly liquid nitrogen) to the skin induces rapid freezing followed by slow thawing. This produces cell injury, vascular stasis and occlusion, and inflammation. The quantity of cryogen delivered onto the skin (dose), technique, duration of thawing and amount of surrounding tissue frozen are dependent on the body region and type of lesion. If clinical diagnosis is not possible, either a skin biopsy or referral to a dermatologist is recommended. We strongly discourage blind treatment of undiagnosed skin lesions.

Familial frontal fibrosing alopecia treated with dutasteride, minoxidil and artificial hair transplantation.

A 46-year-old premenopausal woman presented with familial frontal fibrosis alopecia affecting the temples bilaterally. The diagnosis was confirmed histologically. Her past history included rheumatoid arthritis treated with hydroxychloroquine 400 mg daily and methotrexate 20 mg weekly. Serial intralesional injections of triamcinolone did not limit the progression of hair loss. Treatment with dutasteride 0.1 mg daily and minoxidil 1 mg daily stabilised hair loss and artificial fibre hair transplantation initially led to a satisfactory cosmetic outcome. Unfortunately, the patient developed implant folliculitis uncontrolled by antibiotics, necessitating the removal of the fibres 12 months post-transplantation.