Cutaneous features of TSC when the diagnosis is written on your face. Dr Fiona Browne Consultant Dermatologist
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1 Cutaneous features of TSC when the diagnosis is written on your face Dr Fiona Browne Consultant Dermatologist
2 Tuberous sclerosis complex Hypomelanotic macules Angiofibromas Ungal fibromas Shagreen patch
3
4
5 Hypomelanotic macules Earliest cutaneous feature >90% TSC have >1 1-4% gen population 1-3cm ovoid patches Woods light
6 Hypomelanotic macules Poliosis Multiple guttate/confetti lesions
7 Angiofibromas Age 3-10yrs 80% by adolescence Mild redness firm red/brown firm papules Nasolabial folds cheeks/chin
8 Angiofibromas
9 Fibrous cephalic plaque Angiofibromas
10 Shagreen patch Begin around 2yrs 50% TSC Thickened, elevated, soft skin coloured plaque 1-10cm, can be multiple Usually trunk lumbosacral Collagenoma dermis replaced with thick collagen
11 Shagreen patch
12 Ungal fibromas 11-25% TSC patients At or after puberty 5-10mm smooth flesh coloured lesions emerging from nail fold Can be only sign of disease Solitary lesions in gen population
13 Ungal fibromas Distortion of nail plate grooves
14 Treatment options
15 Surgery Laser Oral mtor inhibitors Topical mtor inhibitors
16 Surgery Indications bleeding, irritation, pain, impaired function and disfigurement Risks recurrence, scarring, sedation/anaesthesia Poor wound healing on mtor inhibitors
17 Pulse Dye Laser Reduces redness of angiofibromas Good for school age children Multiple treatments required GA/Sedation if very young Transient response Ablative Laser Larger angiofibromas in late adolescence/adults General anesthesia Postoperative care can be difficult Pigmentation Scarring Cobblestone texture Recurrence
18 Ablative laser
19 Ablative laser
20 Oral sirolimus British Journal of Dermatology Volume 159, Issue 2, pages , 28 JUN 2008
21 Oral sirolimus Improvement in 78% 25-50% improvement Improvement in 71% Improvement in 60% JAAD 2015.
22 Topical sirolimus Effective Well tolerated No commercial product available What dose, how often?? Concerns re use in pregnancy, skin cancers
23 Sustained clinical effectiveness and favorable safety profile of topical sirolimus (0.4%) for tuberous sclerosis associated facial angiofibroma Journal of the European Academy of Dermatology and Venereology Volume 26, Issue 10, pages , 11 AUG 2011
24 Topical rapamycin for angiofibromas in paediatric patients with tuberous sclerosis: Follow up of a pilot study and promising future directions Australasian Journal of Dermatology Volume 55, Issue 1, pages 63-69, 22 DEC 2013
25 First left right comparative study of topical rapamycin (0.2%) vs. vehicle for facial angiofibromas in patients with tuberous sclerosis complex 12weeks British Journal of Dermatology Volume 169, Issue 6, pages , 2 DEC 2013
26 JEADV 2015
27 Authors Conc. (%) Vehicle No Duration Association with other therapies Posology Haemel et al. 1 Ointment 1 None BD McNamara et al Eucerin 2 8 months 5 months 1 patient added systemic rapamycin DeKlotz et al. 1 Ointment 1 - BD Salido et al. 0.4 Petrolatum 10 9 months - 3/week Mutizwa et al. 0.1 Solution 2 Valeron-Almazan et al. Wataya-Kaneda et al. 10 weeks 23 weeks OD - BD 0.1 Solution 1 3 months - BD 0.2 Tacrolimus oint. 9 3 months 12 weeks Tacrolimus oint. BD Foster et al. 0.1 Petrolatum sol. 4 6 months - BD Wataya-Kaneda et al. Koenig et al. 0.2 Gel, Ointment 2 12 weeks - BD Skincerity 18 6 months - OD Tanaka et al. 0.2 Ointment, Gel weeks - BD Bae-Harboe et al Still ongoing PDL, fractional resurfacing laser, electrosurgery Truchuelo et al. 1 Dexeryl 1 6 weeks - OD Wheless et al. 0.1 Hydrophilic oint. 2 Still ongoing - BD for 2 weeks, then OD Tu et al , Petrolatum 15 (+2) 8 30 months - OD BD Park et al. 0.1 Petrolatum months In 3 patients CO 2 laser BD initially, then 3/week
28 Topical Sirolimus Nova Laboratories Ltd Martin House, Gloucester Crescent Wigston, Leicestershire LE18 4YF Sirolimus ointment 0.1 % in white soft paraffin 30g Community pharmacies will be able to get via their wholesalers
29 25patients, 4-47yrs, median 14yrs Once daily until clear then 3/week 30g/month SPF50 in morning 0.1% sirolimus in evening 30g =341.93; 50g = JAAD 2017
30 Facial Angiofibromas Fading of redness within 1 month Reduction in size and extent takes 3-9mths. No further benefit beyond 9mths Recurrence within 2-7 months Fibrous cephalic plaques 56% partial response (flatter and discoloured) 44% stable/no improvement Shagreen Patch 20% partial reduction (thinner at 6 months) Ungal Fibromas 1 patient minimal improvement at 6 months Hypomelanotic macules Improvement in one black patient at 3 months JAAD 2017
31 Adverse events Acne Folliculitis Mild irritation in 33% - settles after 2-3 days Bloods FBC, Biochem. Normal Serum sirolimus <0.2ng/ml Summary Well tolerated Need to continue treatment longterm Only really useful for angiofibromas Best to start early before lesions reach maximal size Can be used with laser and/or surgery
32 Surgery Wound healing poor when on systemic mtor treatment Laser Pulse Dye redness of angiofibromas Ablative angiofibromas and periungal fibromas. GA or sedation required. Can recur Oral mtor inhibitors Reserved for patients whose internal disease warrants treatment Topical mtor inhibitors Effective Well tolerated No commercial product available Sustained use required
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