Index

acne acne, severe 349-64 cyproterone acetate and isotretinoin effects severe facial 351--4 267-74, 287-91 severe truncal 355-8 definition 215 actinic keratosis, etretinate effects 188, 189, erythromycin and isotretinoin effects 193 293-301 adjuvant arthritis test, retinoid effects 336-8 improvement 296, 297 adverse reactions factors affecting 255 arotinoid 197,331,332 grading assessment 241,242,289,351,359 erythromycin 298, 299 incidence 215 etretinate 27,30,34,40,79,85,86, 197, inflammation 255,261,262,290 277 isotretinoin (Roaccutane) 215-21,223-6, isotretinoin in acne 210, 211, 218, 219, 349-64 233,236,237,295,298,299,306,307, case histories 351-8 351-64 clinical studies 224, 225, 349 dosage 351-7, 364 conventional therapy 217 frequency 225; 226 dose 216,217,221,351-7,359,364 keratinization disorders 324, 364 oral contraceptives 277-82, 364 precautions 364 US use 223, 349, 364 PUVA-etretinate 58, 59 lesion count and isotretinoin 269-71 albumin and isotretinoin dose 272, 273 retinoid effects 96-8 alkaline phosphatase vitamin A dose 2 brush border 169-71 acne conglobata 349-64 intestinal and retinoids 171, 173 isotretinoin dose 231 antibiotics 293-301, 349-57 non-inflammatory and inflammatory lesions anti-inflammatory effects 335--42 234-6 antitumour activities 2, 3, 51, 184, 185, 188, relapse, definition 233 189, 196-8 relapse rate after isotretinoin 231-8 analogue scales and assessment 25,26,317, seborrhoea 235,236 318 acne, cystic and isotretinoin 349-64 arotinoid (Ro 13-6298) 102 back, chest and facial 206, 207 anti-inflammatory effects 329 dose-response study 203-12 cutaneous neoplasia 196-8 failures, relapses and dose 246-8 epidermogenesis effects 126, 127, 129 follow-up study 241-50 epithelial effects 165-75 lesion assessment 205, 206 kidney enzymes 173-5 re-treatment 248, 249 lectin-stimulated lymphocytes 111, 113 sebum secretion 249, 250 lipoxygenase effects 345-7 success incidence 243-6 PMN effects 105, 106, 111-13 acne, papular pustular and isotretinoin use psoriatic arthropathy 329-32 303-9 skin ultrastucture 95-8 doses 304 structure 4 lesion decrease 305, 306 arthralgia, with isotretinoin 362 365 RETINOID THERAPY bacteria, isotretinoin effects 258-63 labelling index 92, 94 basal cell carcinoma, etretinate effects vitamin A retinoid effects 92, 93 188, 189 epidermogenesis Bowen's disease, etretinate effects 188, 190 limb bud growth 123-6 bronchoscopy, morbidity 185 retinoid effects 119-29 brush border enzymes, in situ assay 167 tonofilaments and retinoid 126 ultrastructure 124, 125 cell culture, blastema 120 epidermolysis bullosa, etretinate use 52 retinoid responses 126, 127 epidermolytic hyperkeratosis, isotretinoin cheilitis 218 see also adverse reactions, effects 322, 323 351-8, 360 epithelium chemotaxis enzymatic investigations 167, 169 assay 154, 155 intestinal and kidney, oral retinoid effects etretinate effects on PMN in psoriasis 165-75 153-7 morphological investigation 166, 167 retinoid therapy effects 155-7 erythromycin and isotretinoin effects in acne children, etretinate use 39-42, 50, 63-70 293-301,351-7 cholesterol, serum values and isotretinoin esterase, non-specific and etretinate 96 therapy 237, 238, 271, 272, 307 ethyl retinamide 4 chondrogenesis etretinate 13-18 see also individual conditions, limb buds 121 PUVA retinoid effects on differentiation 121-3, acne 216, 349-64 126-8 adjuvant arthritis test 336-8 ultrastructure 120-3 advantages 33 colon, mucosa morphometric analysis 167-9 anti-keratinizing properties 45, 46 Committee on Safety of Medicines 359, 364 anti-neoplastic 51, 52 contraception 364 assessment, self and investigator 26, 27 cutaneous neoplasia atopy 51 arotinoid effects 195-200 Austrian use 45-53 etretinate effects 187, 195-200 children 39-42,50,63-70 clearing phase and follow-up)l<192 clinical data 40, 41 dose 188 dose 41, 74, 70 types 187 growth and development 40, 41 cyproterone acetate concentration-time profile 12-14 and isotretinoin in acne 267-74,287-91 conditions treated 25, 26 isotretinoin comparison 287-90 delayed hypersensitivity test 336, 337 disadvantages 34 Darier's disease drug comparison 28, 31, 35 etretinate use 46, 61, 62 elimination half-life 18 response to isotretinoin 323 epidermis and subcutis concentrations 3-dehydroretinol:retinol ratio, epidermal in 134, 136-8 lesioned skin 141,142 epithelial effects 165-75 delayed hypersensitivity test, retinoid effects fasting lipids 28, 31 336,337 fatty liver 16 dermatitis, facial, with isotretinoin hyperkeratotic mass removal 48, 49 dermatology and retinoid use 1-5 indications 46, 47 desmosomes, isotretinoin effects 259, 260 kidney enzymes 173-5 Diane, composition 291 killer cell activity 149 dithranol, etretinate comparison 28, 31, 35 lambda-carrageenan pleurisy 337, 338 dry mouth 87 liver function 28, 31 ductal hyperkeratinization, isotretinoin 258, liver storage 15-17 259 long-term use 50, 51, 359 metabolite 13, 14 see also Ro 10-1670 eczema, irritant, with isotretinoin 361 modulation of lymphocyte angiogenesis endothelial cells, isolation and culture- 145 148 enzymes, intestinal and kidney, retinoid palm blistering 49 effects 171-5 photochemotherapy 47 epidermal cell growth, culture precancerous metaplasia in smokers 181-6 366 INDEX

psonasls 11 blood concentrations 18, 19 psoriatic arthropathy 329 and metabolite in acne 19,20 retinol interaction 141 and cyproterone acetate in acne 267-74 side-effects 27, 34, 40, 183, 184, 360 delayed hypersensitivity test 336, 337 spermatological evaluations 161-3 dosage and duration of dosage 359 structure and potency 4, 12, 183 dose and lymphocyte thymidine uptake tissue distribution at autopsy 139, 140 110, 111 tissue storage 16, 17, 133, 135-8 lambda-carrageenan pleurisy 337, 340 treatment effectiveness 33, 349-64 limb bud chondrogenesis 121-3 UK use and experience 25-36, 349-64 lipoxygenase effects 345-7 lymphocyte binding protein 114, 115 fat and etretinate 16, 17, 136, 137, 139 mechanism of action 219-21,255-83 FDA (Food and Drug Administration) 359 4-oxo- structure 12 folliculitis, scalp, with isotretinoin PMN effects in acne and {>soriasis 105 follow-up study, acne 241-50 side-effects in acne 210-21, 218, 219, 225, questionnaire 244, 245 226 treatment 226, 360-3 glucose-6-phosphate dehydrogenase activity in structure 3, 4, 12 ichthyosis and etretinate 94-6 toxic doses, effects on intestine 172 y-glutamyl-O-transferase toxicity 114 erythromycin 299 and isotretinoin dose 210,211,272,273 keratinization disorders glycoprotein synthesis and retinoids 92, 94 assessment of etretinate 27,30 high density lipoprotein-cholesterol and oral retinoid response 101 isotretinoin use 271, 272 keratosis palmaris and plantaris, isotretinoin hyperkeratotic skin 277 response 323, 324 etretinate and inflammation 49, 50 kidney tubule, enzyme measurements in situ hypervitaminosis A syndrome 3, 11 169, 170 children 39 retinoid effects 173-5 and synthetic retinoids 11 lambda-carrageenan pleurisy, retinoid effects ichthyoses in rats 337-41 assessment of etretinate 27, 29 lamellar ichthyoses, etretinate use 46, 47 isotretinoin use 321-5 lichen planus, oral erosive measurements 322 assessment of discomfort 84, 85 types and responses 322 diagnosis and aetiology 83 ichthyosiform erythrodermas etretinate treatment 83-7 bullous, assessment and etretinate 66-9 function tests 86, 87 disorders 69 salivary flow 84, 86 and etretinate 63-70 lipogenesis, cyproterone acetate effects 269 controlled study 67-9 lipoxygenase activity open study 65-7 assay 345, 350 non-bullous, assessment and etretinate retinoid effects 345-7 65-9 solvent extraction technique 346, 347 idiopathic skeletal hyperdystrophy 364 lupus erythematosis, chronic discoid inflammation, isotretinoin role 261,262 etretinate 73-81 intestinal mucosa dearing schedule 74, 78 etretinate effects on morphology and maintenance schedule 74, 78 enzymes 171-3 mechanism of action 80 isotretinoin effects 171-3 hyperkeratotic and inflammatory 74, 78 isotretinoin (13-cis-retinoic acid, Ro 4-3780, patient assessment 73-7 Roaccutane) 18-22 see also individual lymphocytes, peripheral blood conditions angiogenic capability and psoriasis type acne 11,215-21,223-7,349-64 148 dose-response 203-12 cytotoxicity assay 145, 150 adjuvant arthritis test 336-8 etretinate effects in psoriasis 143-50 albumin bound 19 homogenated, centrifugation 103, 104 biliary excretion 21 isolation and culture 103, 144 367 RETINOID THERAPY

isotretinoin binding protein 114, 115 isotretinoin use and remission 323, 324 killer cell activity and etretinate 149, 150 Pityrosporum ovale and isotretinoin 258, lectin-stimulated, retinoid effects 109-12 260,263 retinoid effects 101-17 PMN see polymorphonuclear granulocytes, retinoid incorporation 103, 104 leukocytes Ro 10-1670 effects 109, 110 polymorphonuclear granulocytes (PMN) lymphocyte-induced angiogenesis assay 143 analysis in vitro 102 technique 144, 145 arotinoid effects 105, 106 etretinate effects 104--6 mechanism of action migration 106, 107 anti-inflammatory effects 342 movement and migration 104 antineoplastic effects 197, 198 retinoid target 101, 116 immunomodulation 114 survival time and retinoids 106 isotretinoin 219-21, 255-83 polymorphonuclear leukocytes, chemotaxis in in ichthyoses 325 psoriasis and etretinate 153-7 retinoids 91-8 precancerous bronchial metaplasia, etretinate membrane labilization by retinoids 95, 98 effects 181--6 metaplasia index (MI) 182 precautions, retinoid therapy 364 cigarettes smoked 183 Propionibacterium acnes etretinate 184 isotretinoin effects on density 220, 258, sex related 184, 185 260 methotrexate, etretinate comparison 28, 31, role in acne 255 35 psoriasis microtubule effects 102, 103 assessment of etretinate 27, 29, 48 oxalate-induced radial segmentation test retinoid effects 96--8, 143 102,103 and UV-A, UV-B therapy 48 Ro 10-1670 effects 107, 108 vitamin A dose 2 motretinide psoriasis, chronic plaque adjuvant arthritis test 336--8 PUV-A-etretinate 55--60 delayed hypersensitivity test 336, 337 assessment 57 potency 5 psoriasis, erythrodermic, chemotaxis assess• structure 4 ment and therapy 155 mucus production, limb bud epithelium 128 psoriasis, palmar plantar pustular Munro micro abscesses 153 chemotaxis and therapy response 156 PUVA-etretinate 55--60 Netherton's syndrome and etretinate 50 assessment 58 psoriasis, pustular 48, 101 oral contraceptive steroids chemotaxis assessment and therapy 155 isotretinoin interaction 277-82, 364 psoriatic arthropathy 6~-hydroxycortisol excretion 281 arotinoid response 329-32 plasma ethinyloestradiol 280 dose 330 plasma levonorgestrel 280, 281 HLA-B27 330 plasma concentrations and isotretinoin dose treatment modalities 330 278,279 PUVA, etretinate comparison 35 ornithine decarboxylase, tumour and retinoids PUVA-etretinate therapy 92,94 assessment methods 56 chemotaxis assessment 156 palmo-plantar keratoderma, etretinate effects function tests 59 47,48 psoriasis effectiveness 55--60 phagedenic keratoacanthoma, etretinate regime 154 therapy 188, 190 side-effects 58, 59 pharmacology techniques 56 etretinate 136--42 Pyogenic granuloma, with isotretinoin 362 retinoids 135 13-cis-retinoic acid see isotretinoin pilosebaceous duct, bacterial population and all-trans-retinoic acid isotretinoin 261, 265 lymphocyte responses 114 pityriasis rubra pilaris uses in dermatology 2, 3 etretinate use 47 retinoids 368 INDEX

anti-inflammatory 335-42 role in acne 267 insolubility and binding proteins 108, 109, and success of isotretinoin in acne 249, 250 116 serum, chemoattraction and etretinate in mechanism of action 91-8, 219-21,255-83 psoriasis 155-7 new, selection 3 Sjogren-Larsson syndrome, etretinate and synthetic formulae 3,4 retinol distribution in tissues 139, 140 tissue analysis 136 skin thickness retinol assessment 94, 95 etretinate in autopsy tissue 136, 138-40 etretinate effects 94, 95 role and metabolism 135 isotretinoin effects 362 synthetic retinoid interaction 91, 92 skin ultrastructure and retinoids 95-8 Roaccutane see isotretinoin smokers Ro 4-3780 see isotretinoin HLA frequency 185 Ro 10-1670 (TMMP-RA) precancerous metaplasia and etretinate blood residues 14, 15 181--6 epidermogenesis effects 127 solar keratosis, arotinoid effects 196, 198 etretinate metabolite 15 sperm assessments and etretinate 161-3 inhibition of oxalate-induced radial squamous cell carcinoma, etretinate effects segmentation 103 188, 189 lectin binding capacity 114, 115 Staphylococcus aureus, and isotretinoin 361-2 lipoxygenase effects 345-7 Staphylococcus epidermis, isotretinoin effects liver storage 15-17 258,260 protein binding 108, 109 succinic dehydrogenase in ichthyotic disorders structure 12 and etretinate 94, 95 thymidine uptake in lymphocytes 109, 110 sucrase, ileum concentration and etretinate tissue distribution at autopsy 137,140 170, 171 tissue storage 16, 17 Ro 10-9359 see etretinate tar regime, etretinate comparison 35 Ro 13-6298 see arotenoid teratogenicity, isotretinoin 219,226,227, rosacea 308, 364 isotretinoin treatment 315-19 thyroxine and isotretinoin dose 271, 273 dose and patients 315, 316 Tigason see etretinate lesion change 316 triglycerides photographic assessment 317 erythromycin effects 300 and tetracyclin 315, 318 and isotretinoin 237,271,272,355,357 plasma levels and isotretinoin in acne 211, sclerosing disorders, etretinate use 52 226,237,300, 307, 308 seborrhoea and isotretinoin monitoring 219 acne conglobata 235,236 tumour prophylaxis 51 papular, pustular acne 306 vitamin A see retinol sebum secretion palmitate, teratogenicity 227 cyproterone acetate effects 269,287,288 vitamin A deficiency, signs 1 erythromycin effects 293-8 vitamin D production and isotretinoin isotretinoin 219,269-71, 303 263,264 dose-response 25&-8 rosacea 318 retinoids 97 xeroderma pigmentosum 51,52

369