Data-Medicos 
Dermagic/Express No. 2-80 
27 Octubre 1.999. 27 October 1.999. 

~La Isotretinoina, 
lo Bueno lo Malo y lo Feo ~ 
~The Isotretinoin, 
the Good, the Bad and the Ugly ~ 


EDITORIAL ESPANOL 
================= 
Hola amigos de la red, DERMAGIC en esta ocasion hace una revision de la ISOTRETINOINA, LO BUENO, LO MALO Y LO FEO. Esta popular droga ha traido numerosos beneficios a la humanidad desde que fue introducida al mercado. Primeramente utilizada en el ACNE, posteriormente su uso se fue extendiendo hacia otras patologias DERMATOLOGICAS Y NO DERMATOLOGICAS siendo altamente efectiva. Pero tambien es una GRAN VERDAD de que no se trata de una "moneda de oro", pues SON MUCHOS los efectos adversos que produce principalmente la TERATOGENICIDAD y tambien se ha demostrado que HA FALLADO en donde se consideraba su mayor EFECTO, en el acne. DE modo mis queridos amigos 
DERMAGICOS cuando la vayan a utilizar pongan en el pendulo: LO BUENO, LO 
MALO Y LO FEO de esta medicina. 

Espero disfruten estas 96 apocalipticas !! referencias... 

Bienvenido a DERMAGIC dr: Jorge F. Padilla Henríquez (Venezuela) 

Saludos a todos !!! 

Dr. Jose Lapenta R.,,, 
=====================CORREO - E-MAIL========================= 
From: "raul fachin viso" <[email protected]> 
Subject: Felicitaciones 

José recibe un cordial saludo y mis felicitaciones, asi como de mis colaboradores 
por primer aniversario. 

Tu labor a sido muy importante y de gran ayuda para nuestra formación. 

Continua asi y gracias en nombre de todos. 

amigo 
Raúl Fachín Viso 

EDITORIAL ENGLISH 
================= 
Hello friends of the net, DERMAGIC in this occasion makes a revision of the ISOTRETINOIN, THE GOOD, THE BAD AND THE UGLY thing. This popular drug has brought numerous benefits to the humanity since it was introduced to the market. Firstly used in the ACNE, later on their use was extending toward other pathologies DERMATOLOGICS AND NON DERMATOLOGICS being highly effective. But it is also a GREAT TRUE that it is not a "gold coin", because they are MANY the adverse effects that he produces, mainly the TERATOGENICITY and it has also been demonstrated that it has FAILED where was considered their biggest EFFECT, in the acne. So, my dear DERMAGIC friends when you will use it put in the pendulum: THE GOOD thing, THE BAD thing AND THE UGLY of this medicine. 

I hope you enjoy this 96 apocalyptic !! references... 

Welcome to DERMAGIC dr: Jorge F. Padilla Henríquez (Venezuela) 

Greetings to ALL, !! 
Dr. Jose Lapenta R.,,, =================================================================== 
REFERENCIAS BIBLIOGRAFICAS / BIBLIOGRAPHICAL REFERENCES 
=================================================================== 
============================================================ 
LO BUENO / THE GOOD 
============================================================ 
1.) Oral retinoids in the treatment of seborrhoea and acne. 
2.) Treatment of acne with intermittent isotretinoin. 
3.) Isotretinoin for acne vulgaris. 
4.) [Therapy of severe acne and acne rosacea with oral 13-cis-retinoic acid]. 
5.) Roaccutane treatment guidelines: results of an international survey. 
6.) The treatment of acne fulminans: a review of 25 cases. 
7.) Long-term results of isotretinoin in the treatment of 68 patients with 
hidradenitis suppurativa. 
8.) Multiple keratoacanthomas, giant keratoacanthoma and keratoacanthoma 
centrifugum marginatum: development in a single patient and treatment with 
oral isotretinoin. 
9.) Grover's disease treated with isotretinoin. Report of four cases. 
10.) Transient acantholytic dermatosis treated with isotretinoin. 
11.) A case of bullous transient acantholytic dermatosis. 
12.) Systemic retinoid medication and periodontal health in patients with Papillon-Lefevre syndrome. 
13.) Isotretinoin and recombinant interferon alfa-2a therapy of metastatic malignant melanoma. 
14.) Efficacy of the association of 13-cis-retinoic acid (13cRA) and alpha-interferon 2a (alpha-IFN 2a) in moderate-severe cervical intraepithelial neoplasia (CIN II-III): a pilot study. 
15.) Combined modality therapy for cutaneous T-cell lymphoma. 
16.) Factors associated with the therapeutic efficacy of retinoic acids on malignant lymphomas. 
17.) [A probe using isotretinoin for treatment of poorly differentiated leukemia] 
18.) Treatment of 34 patients with myelodysplastic syndromes with 13-CIS retinoic acid. 
19.) Topical isotretinoin in Darier's disease. 
20.) Topical treatment of ichthyoses and Darier's disease with 13-cis-retinoic acid. A clinical and immunohistochemical study. 
21.) Evaluation of 13-cis retinoic acid in lamellar ichthyosis, pityriasis rubra pilaris and Darier's disease. 
22.) Treatment of pyoderma faciale with isotretinoin in a patient with ulcerative colitis. 
23.) Clinical remission of xeroderma pigmentosum-associated squamous cell carcinoma with isotretinoin and chemotherapy: case report. 
24.) Effect of isotretinoin therapy on natural killer cell activity in patients with xeroderma pigmentosum. 
25.) Evidence for anti-inflammatory activities of oral synthetic retinoids: experimental findings and clinical experience. 
26.) Adult pityriasis rubra pilaris: a 10-year case series. 
27.) Isotretinoin treatment of pityriasis rubra pilaris. 
28.) Phase I trial of retinoic acid and cis-platinum for advanced squamous cell cancer of the head and neck based on experimental evidence of drug synergism. 
29.) Follicular mucinosis successfully treated with isotretinoin. 
30.) Improvement of scleromyxedema associated with isotretinoin therapy. 
31.) [Scleromyxedema therapy with isotretinoin]. 
32.) Comparative study of systemic interferon alfa-2a with oral isotretinoin and oral isotretinoin alone in the treatment of recurrent condylomata accuminata. 
33.) Treatment of condylomata acuminata with oral isotretinoin. 
34.) [Gilbert disease and isotretinoin] 
35.) Zinc pretreatment inhibits isotretinoin teratogenicity and induces embryonic metallothionein in CD-1 mice. 
36.) Negligible systemic absorption of topical isotretinoin cream: implications for teratogenicity. 
37.) Treatment of patients who have fibrodysplasia ossificans progressiva with isotretinoin. 
38.) The cytostatic effect of 9-cis-retinoic acid, tretinoin, and isotretinoin on three different human bladder cancer cell lines in vitro. 
39.) Chemotherapy for disseminated actinic keratoses with 5-fluorouracil and isotretinoin. 
40.) A case of atrophoderma vermiculatum responding to isotretinoin. 
41.) Cutaneous sarcoidosis: complete remission after oral isotretinoin therapy. 
42.) Isotretinoin for refractory lupus erythematosus. 
43.) [Use of oral isotretinoin in the treatment of cutaneous lupus erythematosus]. 
44.) Successful treatment of hypertrophic lupus erythematosus with isotretinoin. 
45.) Isotretinoin in the treatment of systemic sclerosis. 
46.) Isotretinoin and lung function in systemic sclerosis. 
47.) [Keratosis follicularis spinulosa decalvans. Therapy with isotretinoin and etretinate in the inflammatory stage]. 
48.) Treatment of oral erosive lichen planus with systemic isotretinoin. 
49.) Topical application of isotretinoin gel improves oral lichen planus. A 
50.) Systemic isotretinoin treatment of oral and cutaneous lichen planus. 
51.) Variant of keratoderma hereditaria mutilans (Vohwinkel's syndrome). Treatment with orally administered isotretinoin. 
52.) Lupus miliaris disseminatus faciei: efficacy of isotretinoin. 
53.) Epidermolysis bullosa simplex responding to isotretinoin. 
54.) Remission after 13-cis retinoic acid in thrombotic thrombocytopenic purpura. 
============================================================ 
LO MALO/ THE BAD 
============================================================ 
55.) [Acne, hyperandrogenism and oral isotretinoin resistance. 23 cases. Therapeutic implications] 
56.) Predictive factors for failure of isotretinoin treatment in acne patients: results from a cohort of 237 patients. 
57.) [Aggravation of acne by isotretinoin. 6 cases, predictive factors] 
58.) Acne fulminans and erythema nodosum during isotretinoin therapy responding to dapsone. 
59.) [Muscular damage during isotretinoin treatment] 
60.) [Lung disease induced by isotretinoin] 
61.) Vestibular dysfunction in a child with embryonic exposure to accutane. 
62.) Extraspinal enthesopathy caused by isotretinoin therapy. 
63.) Generalized metaphyseal modification with cone-shaped epiphyses following long-term administration of 13-cis-retinoic acid. 
64.) Retinoid-induced ossification of the posterior longitudinal ligament. 
65.) Isotretinoin-induced vasculitis imitating polyarteritis nodosa, with perinuclear antineutrophil cytoplasmic antibody in titers correlated with clinical symptoms. 
66.) Arthropathy associated with cystic acne, hidradenitis suppurativa, and perifolliculitis capitis abscedens et suffodiens: treatment with isotretinoin. 
67.) [Acne in the male resistant to isotretinoin and responsibility of androgens: 9 cases, therapeutic implications (see comments)] 
68.) Ocular side effects of accutane therapy. 
69.) Isotretinoin and curly hair. 
70.) The effect of isotretinoin on biotinidase activity. 
71.) Failure of isotretinoin in Kaposi's sarcoma. 
============================================================ 
LO FEO / THE UGLY 
============================================================ 
72.) Suicide in dermatological patients. 
73.) Young women taking isotretinoin still conceive. Role of physicians in preventing disaster. 
74.) [Isotretinoin (Roaccutane) in women of childbearing age: failure of following prescription guidelines] 
75.) Topical application of 13-cis-retinoic acid in the treatment of chronic plaque psoriasis. 
76.) In vivo effects of 13-cis retinoic acid treatment on the concentration of proteins and lipids in serum. 
77.) Effect of systemic administration of isotretinoin on blood lipids and fatty acids in acne patients. 
78.) Ocular side effects associated with 13-cis-retinoic acid therapy for acne vulgaris: clinical features, alterations of tearfilm and conjunctival flora. 
79.) Retinoids and fibrinolysis. 
80.) Massive isotretinoin intoxication. 
81.) [Isotretinoin (RoAccutane) embryopathy. A case report] 
82.) Similarities in genetic mental retardation and neuroteratogenic Syndromes. 
83.) Development of human papillomavirus type 16 associated squamous cell carcinoma of the scrotum in a patient with Darier's disease treated with systemic isotretinoin. 
84.) Isotretinoin therapy is associated with early skeletal radiographic changes. 
85.) Bone densities in patients receiving isotretinoin for cystic acne. 
86.) Oral isotretinoin therapy in severe acne induces transient suppression of biochemical markers of bone turnover and calcium homeostasis. 
87.) Miliaria crystallina occurring in a patient treated with isotretinoin. 
88.) Steady-state pharmacokinetics of isotretinoin and its 4-oxo metabolite: implications for fetal safety. 
89.) Isotretinoin intoxication in attempted suicide. 
90.) Isotretinoin: possible cause of acute seizure and confusion. 
91.) Median canaliform dystrophy following isotretinoin therapy [letter] 
92.) Mood changes associated with isotretinoin and substance abuse [letter] 
93.) Urethritis associated with isotretinoin therapy [letter] 
94.) Renal impairment induced by isotretinoin [letter] 
95.) Isotretinoin-induced pemphigus. 
96.) Acute arthritis after isotretinoin. 
============================================================ 
LO BUENO / THE GOOD 
============================================================ 
1.) Oral retinoids in the treatment of seborrhoea and acne. 
============================================================ 
Author 
Orfanos CE; Zouboulis CC 
Address 
Department of Dermatology, University Medical Center Benjamin Franklin, 
Free University of Berlin, Germany. 
Source 
Dermatology, 196(1):140-7 1998 
Abstract 
Isotretinoin is an extremely effective drug if given systemically in severe 
forms of seborrhoea and acne, being the only retinoid with potent 
sebostatic properties. Its unique activity on the sebaceous gland still 
remains unclear since isotretinoin barely binds to cellular 
retinoic-acid-binding proteins and to retinoic acid receptors. Its 
bioavailability is approximately 25% and can be increased by food 1.5-2 
times; after 30 min, the drug is detectable in the blood and maximal 
concentrations are reached 2-4 h after oral intake. The major metabolites 
of isotretinoin in blood are 4-hydroxy- and 4-oxo-isotretinoin, while 
several glucuronides are detectable in the bile. 4-Oxo-isotretinoin is 
present in plasma in a 2- to 4-fold higher concentration 6 h after a single 
dose. Steady-state concentrations appear after 1 week. The half-life 
elimination rate of the parent compound ranges from 7 to 37 h while that of 
some metabolites does so from 11 to 50 h. Isotretinoin crosses the placenta 
and is recognized as a strong teratogenic compound. About 10-30% of the 
drug is metabolized via its isomer tretinoin. Excretion of isotretinoin 
occurs after conjugation with the faeces or after metabolization with the 
urine. The epidermal levels of isotretinoin are rather low and no 
progressive accumulation, either in serum or in the skin, is found. After 
discontinuation of therapy, isotretinoin disappears from serum and skin 
within 2-4 weeks. Isotretinoin is the most effective drug in reducing 
sebaceous gland size (up to 90%) by decreasing proliferation of basal 
sebocytes, suppressing sebum production and inhibiting sebocyte 
differentiation in vivo. The molecular basis for its antisebotrophic 
activity has not been fully elucidated. Isotretinoin also exhibits 
anti-inflammatory activities. Systemic isotretinoin is today the regimen of 
choice in severe seborrhoea, since it reduces sebocyte lipid synthesis by 
75% with daily doses as low as 0.1 mg/kg after 4 weeks. Patients who have 
received oral isotretinoin therapy for seborrhoea do not usually experience 
a relapse for months or years. In severe acne, a 6- to 12-month treatment 
with isotretinoin 1 mg/kg/day reduced to 0.5 or 0.2 mg/kg/day according to 
the response is recommended (cumulative dose of > 120 mg/kg). Contraception 
is essential during isotretinoin treatment in women of childbearing age 1 
month before, during and for 3 months after discontinuation of treatment. 

============================================================ 
2.) Treatment of acne with intermittent isotretinoin. 
============================================================ 
Goulden V; Clark SM; McGeown C; Cunliffe WJ 
Dermatology Department, Leeds General Infirmary, UK. 
Br J Dermatol (ENGLAND) Jul 1997 137 (1) p106-8 ISSN: 0007-0963 
Language: ENGLISH 
Document Type: CLINICAL TRIAL; JOURNAL ARTICLE 
Journal Announcement: 9711 
Subfile: INDEX MEDICUS 
Adults with acne represent an increasingly important population of acne 
sufferers referred for treatment. Acne, in these patients, is generally 
mild or moderate in severity but tends to be resistant to conventional 
antibiotic therapy. A study was carried out to assess the efficacy of 
intermittent moderate dose isotretinoin as a treatment for acne. Eighty 
consecutive patients, over the age of 25 years, referred with acne 
unresponsive to, or relapsing rapidly after three or more courses of 
conventional antibiotic therapy were recruited. Acne severity was 
assessed on the face, chest and back using the Leeds grading scale and the 
number of inflamed lesions was counted at the site showing the highest 
acne grade. The patients were 22 men and 58 women. The treatment regimen 
consisted of isotretinoin, 0.5 mg/kg per day for 1 week in every 4 week 
for a total period of 6 months. Seventy-five patients completed the study. 
The therapy was very well tolerated with mild cheilitis as the only side- 
effect. At the end of treatment, both total acne grade and lesion counts 
were significantly reduced (P < 0.0001). The acne had resolved in 68 
(88%) patients. Twelve months after treatment, acne grades and inflamed 
lesion counts remained significantly improved (P < 0.0001) in the 68 
patients who responded; however, 26 (39%) patients had relapsed. There 
was a significantly higher incidence of relapse in patients with 
predominantly truncal acne (P = 0.01). Patients who relapsed also had a 
significantly higher total acne grade, lesion count (P < 0.0001) and sebum 
excretion rate (P < 0.001) compared with those whose acne resolved. This 
study suggests that intermittent moderate dose isotretinoin may be a cost- 
effective alternative to full dose isotretinoin in a carefully selected 
group of adult patients with-acne. Selection criteria should include 
predominantly facial acne, total acne grade less than 1, inflamed lesion 
count less than 20 and sebum excretion rate less than 1.25 micrograms/cm2 
per min. 

============================================================ 
3.) Isotretinoin for acne vulgaris. 
============================================================ 
AU: al-Khawajah-MM 
AD: Department of Medicine, College of Medicine, King Saud University, 
Riyadh, Saudi Arabia. 
SO: Int-J-Dermatol. 1996 Mar; 35(3): 212-5 
ISSN: 0011-9059 
PY: 1996 
LA: ENGLISH 
CP: UNITED-STATES 
AB: BACKGROUND. The clinical efficacy of oral isotretinoin in the treatment 
of severe acne is now well established and so are the clinical and 
laboratory adverse effects of the drug. Isotretinoin was first introduced 
in Saudi Arabia late in 1987. In this 7-year retrospective study, efficacy 
and side effects of isotretiunoin are reviewed in Saudi patients with acne 
vulgaris seen in a university skin clinic in Riyadh, Saudi Arabia. 
MATERIALS AND METHODS. A total of 262 patients had been treated with 
isotretinoin. Their case records were studied with reference to demographic 
data, clinical findings, dosage of isotretinoin, response to the drug, and 
the prevalence and severity of clinical and laboratory adverse effects. 
RESULTS. Only 156 case records (69.9% women) could be evaluated. Most 
patients received 0.60 to 0.75 mg of isotretinoin per kg per day for a 
period ranging from 16 to 35 weeks (mean +/- SD: 21.2 +/- 3.3 weeks); a 
total cumulative dose of 75 to 146 mg per kg (mean +/- SD: 104 +/- 10.6 mg 
per kg). Approximately 56% of the patients had therapy-resistant moderate 
acne and only 14% had nodulocystic acne. Of the patients, 90.4% had an 
excellent response and 3.8% were poor responders. Adverse effects occurred 
in 99% of the patients, but in no case did they lead to discontinuation of 
the drug. Except for minor differences in prevalence, the clinical side 
effects were similar to those reported in the literature. Elevation of 
plasma triglyceride levels was the most significant laboratory adverse 
effect. CONCLUSIONS. This is the first report on the experience with 
isotretinoin in the treatment of acne in the Middle East. Moderate doses of 
isotretinoin are well tolerated and produce excellent results in Saudi 
patients with acne. 

============================================================ 
4.) [Therapy of severe acne and acne rosacea with oral 13-cis-retinoic acid]. 
============================================================ 
Acta Vitaminol Enzymol 1984;6(4):325-37 

Gandola M 
Forty patients suffering of different forms of acne (papulo-pustular, 
nodulo-cystic, conglobata, rosacea), all in severe conditions and 
non-responding to other treatments, have been administered 13-cis-retinoic 
acid p.o. The treatment resulted in a complete and ultimate healing in 31 
pts (77.5%) and a marked amelioration in the remaining 9 cases. The initial 
drug dosage was 40 mg/die (an average of 0.66 mg/kg/die) but it was reduced 
along the treatment to 2.5 mg/die, a still effective dose. The average 
treatment duration was 24 weeks (range: 12 to 40). The tolerance was 
generally excellent, but some adverse effect have been recorded, mainly 
localized in the skin and mucosa. Increases of total serum cholesterol (66% 
of the cases) and of triglyceride (72%) level have been observed. This 
effect was reversible at the end of the treatment. As a conclusion we can 
confirm that the 13-cis-retinoic acid is the most effective drug for the 
pharmacotherapy of severe acne. 

============================================================ 
5.) Roaccutane treatment guidelines: results of an international survey. 
============================================================ 
Author 
Cunliffe WJ; van de Kerkhof PC; Caputo R; Cavicchini S; Cooper A; Fyrand 
OL; Gollnick H; Layton AM; Leyden JJ; Mascar&acute;o JM; Ortonne JP; Shalita A 
Address 
Leeds General Infirmary, UK. 
Source 
Dermatology, 194(4):351-7 1997 
Abstract 
BACKGROUND: Oral isotretinoin (Roaccutane) revolutionized the treatment of 
acne when it was introduced in 1982. METHODS: Twelve dermatologists from 
several countries with a special interest in acne treatment met to formally 
review the survey of their last 100 acne patients treated with oral 
isotretinoin. The primary purpose of the survey was to identify the types 
of acne patients who were prescribed oral isotretinoin and how the patients 
were managed. RESULTS: Of the 1,000 patients reviewed, 55% of those who 
received oral isotretinoin had those indications treated historically, i.e. 
severe nodular cystic acne or severe inflammatory acne, not responding to 
conventional treatment. Forty-five percent of patients who were prescribed 
oral isotretinoin however had either moderate or mild acne. Most patients 
in this group had moderate acne (85%). However, 7.3% had mild acne on 
physical examination. The criteria for prescribing oral isotretinoin in 
this less severe group of patients included acne that improves < 50% after 
6 months of conventional oral antibiotic and topical combination therapy, 
acne that scars, acne that induces psychological distress and acne that 
significantly relapses during or quickly after conventional therapy. 
Treatment is usually initiated at daily doses of 0.5 mg/kg (but may be 
higher) and is increased to 1.0 mg/kg. Most of the physicians aimed to 
achieve a cumulative dose of > 100-120 mg/kg. Mucocutaneous side-effects 
occur frequently but are manageable while severe systemic side-effects are 
rarely problematic (2%). The teratogenicity of oral isotretinoin demands 
responsible consideration by both female patients and their physicians. 
Significant cost savings when treating acne patients with oral isotretinoin 
as compared to other treatment modalities were further proven in this 
study. CONCLUSIONS: Our recommendation is that oral isotretinoin should be 
prescribed not only to patients with severe disease but also to patients 
with less severe acne, especially if there is scarring and significant 
psychological stress associated with their disease. Acne patients should, 
where appropriate, be prescribed isotretinoin sooner rather than later. 
Language 

============================================================ 
6.) The treatment of acne fulminans: a review of 25 cases. 
============================================================ 
Br J Dermatol 1999 Aug;141(2):307-309 

Seukeran DC, Cunliffe WJ 
Department of Dermatology, Leeds General Infirmary, Leeds LS1 3EX, U.K. 

The treatment of acne fulminans has been difficult. It is difficult to 
perform a controlled treatment trial due to the rarity of the complication. 
However, it is possible to compare four different therapeutic regimens 
which have evolved with time in the management of 25 patients over a period 
of 25 years. Oral antibiotics produced a slow response in the resolution of 
acne and systemic symptoms. The addition of a systemic steroid produced a 
quick resolution of systemic features, but the time until resolution of the 
acne was longer than when it was used in combination with oral 
isotretinoin. The protocols which used a combination of prednisolone and 
isotretinoin led to faster control of systemic features as well as 
clearance of acne when compared with other protocols. This was particularly 
so if the oral steroid was used sooner rather than later. We conclude that 
the preferred treatment of acne fulminans is oral prednisolone 0.5-1 mg/kg 
daily for 4-6 weeks (thereafter slowly reduced to zero) with oral 
isotretinoin being added to the regimen at the fourth week, initially at 
0.5 mg/kg daily and gradually increased to achieve complete clearance. 

============================================================ 
7.) Long-term results of isotretinoin in the treatment of 68 patients with 
hidradenitis suppurativa. 
============================================================ 
Author 
Boer J; van Gemert MJ 
Address 
Department of Dermatology, Deventer Hospital, The Netherlands. 
Source 
J Am Acad Dermatol, 40(1):73-6 1999 Jan 
Abstract 
BACKGROUND: Oral isotretinoin has been used to treat mild to severe 
hidradenitis suppurativa (HS). OBJECTIVE: We reviewed the results of 
low-dose isotretinoin for 4 to 6 months in the treatment of 68 patients 
with HS. METHODS: This is a retrospective study. Data are presented in 
terms of response rate, long-term follow-up, and the relation between 
response rate and severity. RESULTS: In 16 patients (23.5%), the condition 
completely cleared during initial therapy and 11 patients (16.2%) 
maintained their improvement during the follow-up period. Treatment was 
more successful in the milder forms of HS. CONCLUSION: Monotherapy with 
isotretinoin for patients with HS usually has a limited therapeutic effect. 

============================================================ 
8.) Multiple keratoacanthomas, giant keratoacanthoma and keratoacanthoma 
centrifugum marginatum: development in a single patient and treatment with 
oral isotretinoin. 
============================================================ 
AU: Schaller-M; Korting-HC; Wolff-H; Schirren-CG; Burgdorf-W 
AD: Department of Dermatology, Ludwig-Maximilians-University, Munich, Germany. 
SO: Acta-Derm-Venereol. 1996 Jan; 76(1): 40-2 
ISSN: 0001-5555 
PY: 1996 
LA: ENGLISH 
CP: NORWAY 
AB: A 78-year-old man is described, who over 18 years developed three 
different types of keratoacanthoma: multiple keratoacanthomas, 
keratoacanthoma centrifugum marginatum and giant keratoacanthoma. 
Histological examination of the different neoplasms showed similar changes, 
all typical of a keratoacanthoma. In situ hybridisation revealed no human 
papilloma virus in the tumours. Complete examination showed no associated 
internal malignancy. After repeated surgical treatment oral isotretinoin 
treatment was administered (1 mg/kg per day). This treatment produced 
clearing of existing keratoacanthomas and, during a period of 2 months, 
further keratoacanthoma formation was completely suppressed. Treatment was 
stopped after 3 months by the patient because of side-effects. Numerous 
keratoacanthomas developed during the following 6 weeks. 

============================================================ 
9.) Grover's disease treated with isotretinoin. Report of four cases. 
============================================================ 
J Am Acad Dermatol 1985 Jun;12(6):981-4 

Helfman RJ 
Grover's disease (transient acantholytic dermatosis; TAD), a disorder of 
unknown etiology, may resemble Darier's disease and frequently resists 
conventional therapies. The lesions can be extensive and pruritus can be a 
prominent feature. Four patients with Grover's disease were treated with 
isotretinoin. Three patients with relatively acute disease responded with 
remissions of up to 10 months after treatment. One patient with disease of 
8 months' duration obtained partial relief but experienced a relapse when 
medication was stopped. 

============================================================ 
10.) Transient acantholytic dermatosis treated with isotretinoin. 
============================================================ 
J Am Osteopath Assoc 1990 Feb;90(2):179-82 

Mancuso A, Cohen EH 
Transient acantholytic dermatosis is a self-limiting benign disease. It is 
characterized by multiple pruritic erythematous papules and papulovesicles 
found predominantly on the trunk and extremities. This primary acantholytic 
dermatosis affects individuals older than 40 years. We present a case study 
of an individual who received a regimen of isotretinoin (Accutane) for 
treatment of severe pruritus after conventional forms of therapy failed to 
alleviate his condition and abate the formation of new lesions. 

============================================================ 
11.) A case of bullous transient acantholytic dermatosis. 
============================================================ 
J Dermatol 1994 Mar;21(3):194-6 

Yoo JH, Cho KH, Youn JI 
Department of Dermatology, Seoul National University College of Medicine, 
Korea. 

We report a case of a bullous variant of transient acantholytic dermatosis 
in a 59-year-old female. Each bullous lesion lasted several weeks and 
healed without scarring. The lesions were migratory and recurrent without a 
cleared period. Histopathologic examination revealed an intraepidermal 
vesicle low in the epidermis. The lesions cleared after 2 months of 
isotretinoin therapy. 

============================================================ 
12.) Systemic retinoid medication and periodontal health in patients with 
Papillon-Lefevre syndrome. 
============================================================ 
AU: Lundgren-T; Crossner-CG; Twetman-S; Ullbro-C 
AD: Department of Dentistry, King Faisal Specialist Hospital and Research 
Centre, Riyadh, Kingdom of Saudi Arabia. 
SO: J-Clin-Periodontol. 1996 Mar; 23(3 Pt 1): 176-9 
ISSN: 0303-6979 
PY: 1996 
LA: ENGLISH 
CP: DENMARK 
AB: Periodontal health in relation to systemic retinoid medication was 
evaluated retrospectively in patients with Papillon-Lefevre Syndrome (PLS). 
The material consisted of 18 children/young adults ranging from 8 to 28 
years of age, all with a confirmed diagnosis of PLS. 9 participants, 
comprising a medication group, had been on long-term (range 1.5-9 years) 
retinoid medication for their cutaneous lesions. The remaining 9 served as 
controls. Regardless of whether or not retinoid medication was received, 
every patient experienced an early and devastating periodontitis, with 
atypical edematous and erythematous gingiva, suppuration from deep gingival 
pockets and premature loss of teeth. No correlation could be found between 
the severity of skin involvement and the severity of periodontal 
involvement. An improvement with age could be seen for the cutaneous 
lesions but not for the periodontal condition. Systemic medication with 
retinoids had a favorable therapeutic effect on cutaneous lesions, and no 
severe complication/side effect could be seen after several years of 
continuous use. However, from the results of this study it can be concluded 
that, at least in a situation with poor compliance of daily oral home-care, 
no positive effect on the periodontal health in patients with PLS could be 
seen by the retinoid medication. 

============================================================ 
13.) Isotretinoin and recombinant interferon alfa-2a therapy of metastatic 
malignant melanoma. 
============================================================ 
AU: Triozzi-PL; Walker-MJ; Pellegrini-AE; Dayton-MA 
AD: Arthur G. James Cancer Hospital and Research Institute, The Ohio State 
Comprehensive Cancer Center, Columbus, Ohio, USA. 
SO: Cancer-Invest. 1996; 14(4): 293-8 
ISSN: 0735-7907 
PY: 1996 
LA: ENGLISH 
CP: UNITED-STATES 
AB: Twenty-five patients with metastatic malignant melanoma were treated 
with isotretinoin (13-cis-retinoic acid) orally at 1 mg/kg daily and 
recombinant interferon alfa-2a (INF-alpha) subcutaneously at 3 million 
units daily for 16-48 weeks. Therapy was well tolerated; fatigue and 
hyperlipidemia were the most frequent dose-limiting toxicity and 
necessitated dose reductions in 14 patients. Two patients achieved a 
complete response, and 3 responded partially for a total response rate of 
20% (95% confidence interval: 4-36%). Responses occurred primarily in 
patients with limited tumor burden and disease confined to the skin and 
lymph nodes. Significant elevations in peripheral blood 
2'-5'-oligoadenylate synthetase activity and natural killer activity were 
observed with therapy. The magnitude of these changes, however, was not 
predictive of response. Biopsy specimens of two responding lesions showed 
extensive necrosis of tumor. One specimen showed large aggregates of 
melanophages in association with tumor. The combination of isotretinoin and 
IFN-alpha is an active, easily administered regimen with acceptable 
toxicity for metastatic malignant melanoma. 

============================================================ 
14.) Efficacy of the association of 13-cis-retinoic acid (13cRA) and 
alpha-interferon 2a (alpha-IFN 2a) in moderate-severe cervical 
intraepithelial neoplasia (CIN II-III): a pilot study. 
============================================================ 
AU: Toma-S; Ragni-N; Raffo-P; Boselli-F; Gustavino-C; Rugiati-S; 
Formelli-F; Palumbo-R; Rosso-R; De-Cecco-L 
AD: National Institute for Cancer Research-IST, Institute of Oncology, 
University of Genova, Italy. 
SO: Anticancer-Res. 1996 Mar-Apr; 16(2): 931-6 
ISSN: 0250-7005 
PY: 1996 
LA: ENGLISH 
CP: GREECE 
AB: Recent in vitro studies have suggested a possible therapeutic synergism 
between alpha-IFN 2a and 13cRA in certain neoplasias, while encouraging in 
vivo findings strongly support the enhanced effectiveness of the two agents 
when used in combination. The specific aim of our study was to evaluate the 
efficacy and the toxicity of the association of 13cRA and alpha-IFN 2a in 
patients with CIN II and CIN III who refused surgical treatment. Twenty-one 
patients (aged between 25 and 58 years), of which 14 were CIN II and 7 CIN 
III, entered the study. 13cRA (orally at 0.5-1 mg/Kg/day) and alpha-IFN 2a 
(intramuscular at 3x10(6) I.U./day for the first 15 days, then 3 times/week 
for the following four weeks) were administered simultaneously for eight 
consecutive weeks. 13/21 (62%) histologically verified objective responses 
(6 complete and 7 partial) were achieved. We also obtained 8 stable 
diseases. Compliance was generally good and no delays in therapy due to 
toxicity were recorded (except for two patients presenting WHO degree III 
cutaneous and mucosal toxicity which regressed one week after suspending 
treatment). Human Papilloma Virus (HPV) was initially detected in 16/21 
(76%) patients, while HPV negativization after treatment was observed in 
3/16 (19%). Although preliminary and requiring long-term assessment, the 
encouraging results of this study confirm the need for further 
investigation on the role of systemic medical therapy in the treatment of 
CINs. 

============================================================ 
15.) Combined modality therapy for cutaneous T-cell lymphoma. 
============================================================ 
AU: Duvic-M; Lemak-NA; Redman-JR; Eifel-PJ; Tucker-SL; Cabanillas-FF; 
Kurzrock-R 
AD: Department of Medical Specialties, University of Texas, M. D. Anderson 
Cancer Center, Houston 77030, USA. 
SO: J-Am-Acad-Dermatol. 1996 Jun; 34(6): 1022-9 
ISSN: 0190-9622 
PY: 1996 
LA: ENGLISH 
CP: UNITED-STATES 
AB: BACKGROUND: Cutaneous T-cell lymphoma (CTCL) may respond to many 
therapies, but long-term disease-free survival is uncommon. Patients with 
advanced disease have a median survival of approximately 3 years. 
OBJECTIVE: Our purpose was to combine known effective agents sequentially 
to determine whether we could achieve remission in more patients or for 
longer duration. METHODS: Patients with mycosis fungoides (n = 23) or 
Sezary syndrome (n = 5) were treated with 4 months of recombinant 
interferon alfa together with isotretinoin, followed by total skin electron 
beam therapy alone (for stage I to II disease) or preceded by chemotherapy 
(for stage III to IV disease). Maintenance therapy consisted of interferon 
for 1 year and topical nitrogen mustard for 2 years. RESULTS: Twenty-eight 
patients were treated. The overall response rate (complete and partial 
remissions) was 82%. Although the median duration of remission was 5 months 
in patients with stage III to IV disease, two patients remain in complete 
remission at 39 + and 46 + months. In patients with stage I to II disease 
the median duration of remission has not been reached at a median follow-up 
of 18 months. Five patients, all with stage III to IV disease, have died. 
Overall, the regimen was well tolerated with one treatment-related death 
from neutropenic sepsis. CONCLUSION: Combined modality therapy may be 
effective for the treatment of CTCL with similar response rates to other 
current therapies. 

============================================================ 
16.) Factors associated with the therapeutic efficacy of retinoic acids on 
malignant lymphomas. 
============================================================ 
Cheng AL; Chuang SE; Su IJ 
Department of Internal Medicine, National Taiwan University Hospital, 
Taipei, Taiwan, ROC. 
J Formos Med Assoc (TAIWAN) Jul 1997 96 (7) p525-34 ISSN: 0929-6646 
Language: ENGLISH 
Document Type: JOURNAL ARTICLE 
Journal Announcement: 9711 
Subfile: INDEX MEDICUS 
We recently reported the successful use of retinoic acids in the 
treatment of refractory lymphoma. The biologic determinants predicting 
response of lymphomas to retinoic acid remain unknown. This study was 
conducted to explore this question using in vitro models. Sensitivity of 
representative lymphoma cells to 13-cis-retinoic acid was determined. 
Sensitive and resistant cell lines were then compared for their baseline 
and/or retinoic-acid-regulated expression of total cellular retinoic acid 
binding protein, retinoic acid receptor (RAR)-alpha, RAR-beta, RAR-gamma 
mRNA, retinoid X receptor (RXR)-alpha, RXR-beta, RXR-gamma mRNA, 
transforming growth factor (TGF)-beta 1 and TGF-beta 1 receptors, and Fas 
(Apo-I) mRNA. The results showed that four of five T, two of three 
Hodgkin's, and none of six B cell lymphoma cell lines were sensitive (IC30 
< 1.5 mmol/L) to 13-cis-retinoic acid. Further analyses revealed several 
of the above-mentioned parameters may be relevant to retinoic acid 
sensitivity. Baseline expression of TGF-beta 1 receptors was present in 
all of the five sensitive cell lines examined, but in only one of the four 
resistant cell lines. The correlation of Fas expression and retinoic acid 
sensitivity was good for B cell lines, but not apparent for T cell or 
Hodgkin's cell lines. On exposure to retinoic acid, an immediate and 
prolonged upregulation of RAR-alpha mRNA expression, lasting for more than 
12 hours, occurred in all sensitive cell lines, but only minimal or 
transient induction was seen in resistant cells. Together, these data 
suggested that; 1) retinoic acid has a preferential effect on T cell and 
Hodgkin's lymphoma cell lines; 2) autoregulation of RAR-alpha by retinoic 
acids, and the presence of TGF-beta 1 receptors may be relevant to the 
response of lymphomas to treatment with retinoic acids. 

============================================================ 
17.) [A probe using isotretinoin for treatment of poorly differentiated 
leukemia] 
============================================================ 
Proba zastosowania izotretynoiny w leczeniu biaLaczki 
niskozro.ANG.znicowanokomorkowej. 
Duda-Krol W; Jorasz I; Lewandowska D; Polubiec A 
Katedry i Kliniki Chorob Wewnetrznych i Hematologii Akademii Medycznej w 
Warszawie. 
Wiad Lek (POLAND) 1996 49 (7-12) p92-4 ISSN: 0043-5147 
Language: POLISH Summary Language: ENGLISH 
Document Type: 
JOURNAL ARTICLE English Abstract 
Journal Announcement: 9710 
Subfile: INDEX MEDICUS 
Isotretinoin (Roaccutane) was used in a patient with low differentiated 
cell leukemia. Poor general condition, very low blood cell count as well 
patient's lack of consent made chemotherapy impossible. The effect of 
isotretinoin treatment was full hematological and clinical remission. The 
general patient's condition did not require additional medication. 

============================================================ 
18.) Treatment of 34 patients with myelodysplastic syndromes with 13-CIS 
retinoic acid. 
============================================================ 
AU: Bourantas-KL; Tsiara-S; Christou-L 
AD: Department of Internal Medicine, University of Ioannina, Greece. 
SO: Eur-J-Haematol. 1995 Oct; 55(4): 235-9 
ISSN: 0902-4441 
PY: 1995 
LA: ENGLISH 
CP: DENMARK 
AB: Thirty-four patients with myelodysplastic syndromes, 23 men and 11 
women, aged between 47 and 80 years, with all types of myelodysplastic 
syndromes were treated with 13-cis-retinoic acid. The dose of retinoic acid 
ranged between 10 and 60 mg/m2/daily and was administered in combination 
with vitamin E to diminish side effects. The duration of treatment was 3 
months to 5 years. Partial remission was achieved in 4 patients, 1 with RA 
type, 2 with RAEB and 1 with CMML. Survival ranged from 1 to 5 years. 
Patients who received retinoic acid developed mild side effects. In 
conclusion, the administration of 13-cis-retinoic acid improves the 
hematological picture in a small number of MDS patients (11.7%). 

============================================================ 
19.) Topical isotretinoin in Darier's disease. 
============================================================ 
AU: Burge-SM; Buxton-PK 
AD: Department of Dermatology, Stoke Mandeville Hospital NHS Trust, 
Aylesbury, Bucks, UK. 
SO: Br-J-Dermatol. 1995 Dec; 133(6): 924-8 
ISSN: 0007-0963 
PY: 1995 
LA: ENGLISH 
CP: ENGLAND 
AB: Topical 0.05% isotretinoin (Isotrex gel) was used to treat a test patch 
of skin in 11 patients with Darier's disease. Hyperkeratosis and papules 
improved in six patients after treatment for 3 months. Erythema, burning 
and irritation were common adverse effects, and these were severe in three 
patients, one of whom stopped treatment. Patients with mild Darier's 
disease may find topical isotretinoin helpful, but it is likely that most 
patients with widespread disease will require treatment with systemic 
retinoids. 

============================================================ 
20.) Topical treatment of ichthyoses and Darier's disease with 
13-cis-retinoic acid. A clinical and immunohistochemical study. 
============================================================ 
Arch Dermatol Res 1993;285(4):221-6 

Steijlen PM, Reifenschweiler DO, Ramaekers FC, van Muijen GN, Happle R, 
Link M, Ruiter DJ, van de Kerkhof PC 
Department of Dermatology, University Hospital Nijmegen, The Netherlands. 

In a bilaterally paired double-blind comparison study, a cream containing 
0.1% 13-cis-retinoic acid (13-cis-RA) and cream base only were applied over 
4 weeks in seven patients with non-erythrodermic lamellar ichthyosis 
(NELI), two patients with Darier's disease and one patient with autosomal 
dominant ichthyosis vulgaris (ADIV). In two patients with NELI and two 
patients with Darier's disease a half-side effect was observed in favour of 
the side treated with 13-cis-RA. In three patients an induction of 
cytokeratin-4, and in one of these patients expression of cytokeratin-13, 
were observed after therapy. Topical 13-cis-RA appears to be a promising 
approach in the treatment of disorders of keratinization. The selective 
modulation of the cytokeratin pattern may provide an immunohistochemical 
tool to investigate the mode of action of retinoids. 

============================================================ 
21.) Evaluation of 13-cis retinoic acid in lamellar ichthyosis, pityriasis 
rubra pilaris and Darier's disease. 
============================================================ 
Cutis 1980 Apr;25(4):380-1, 385 

Gilgor RS, Chiaramonti A, Goldsmith LA, Lazarus GS 
A new synthetic oral retinoid, 13-cis retinoic acid, is fairly well 
tolerated in patients and appears to be effective in those with Darier's 
disease and lamellar ichthyosis. It is less effective in those with 
pityriasis rubra pilaris. The mechanism of action of 13-cis retinoic acid 
in disorders of keratinization is unknown at the present time; however, it 
does not appear to cause lysosomal proliferation in therapeutic doses. 

============================================================ 
22.) Treatment of pyoderma faciale with isotretinoin in a patient with 
ulcerative colitis. 
============================================================ 
Cutis 1999 Aug;64(2):107-9 

Rosen T, Unkefer RP 
Baylor College of Medicine, Houston, Texas, USA. 

The explosive onset of fluctuant facial papulonodules, usually in young 
women, is characteristic of pyoderma faciale. This disorder is neither a 
true pyoderma nor a variant of acne, but rather a severe form of rosacea. 
The most effective therapeutic modality appears to be isotretinoin, 
especially if preceded by a brief course of oral corticosteroids or a short 
interval of application of potent topical corticosteroids. Despite our 
concern about the potential adverse effects of systemic retinoids on 
underlying inflammatory bowel disease, isotretinoin was given to a patient 
with refractory pyoderma faciale. Response was dramatic, and no ill effects 
were encountered. 

============================================================ 
23.) Clinical remission of xeroderma pigmentosum-associated squamous cell 
carcinoma with isotretinoin and chemotherapy: case report. 
============================================================ 
J Chemother 1999 Aug;11(4):313-7 

Saade M, Debahy NE, Houjeily S 
Division of Hematology-Oncology, Lebanese University Medical School, 
Beirut. [email protected] 

We report the case of a 7-year old boy with xeroderma pigmentosum and a 
large squamous cell carcinoma of the cheek. He received a combination of 
isotretinoin (1 mg/kg/day) and chemotherapy for a period of 3 months and 
showed complete remission of the tumor. Treatment modalities of 
malignancies in xeroderma pigmentosum are reviewed and discussed in 
relation to the literature. The advantages of our protocol were emphasized 
because of the rapid improvement in a short time with minimal side effects. 

============================================================ 
24.) Effect of isotretinoin therapy on natural killer cell activity in 
patients with xeroderma pigmentosum. 
============================================================ 
Author 
Anolik JH; Di Giovanna JJ; Gaspari AA 
Address 
Department of Dermatology, National Institute of Arthritis, Musculoskeletal 
and Skin Diseases, National Institutes of Health, USA. 
Source 
Br J Dermatol, 138(2):236-41 1998 Feb 
Abstract 
Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder 
characterized by sun sensitivity, defective DNA repair, markedly increased 
susceptibility to skin cancer, and a variety of immunological defects, 
including defective natural killer (NK) cell activity. Retinoid therapy has 
been demonstrated to protect effectively against the development of skin 
cancers in patients with XP, although its mechanism of action is unknown. 
We describe a series of eight XP patients, six of whom were given oral 
isotretinoin. The NK cell activity was not affected by low-dose 
isotretinoin, i.e. 0.5 mg/kg per day. However, higher doses of 
isotretinoin, e.g. 1.0 mg/kg per day, produced a significant decrease in NK 
cell function, at the same time as producing a reduction in the frequency 
of development of skin cancers. Retinoid therapy may have a skin cancer 
preventing effect by enhancing other immune effector mechanisms or via 
epithelial cell differentiation. 

============================================================ 
25.) Evidence for anti-inflammatory activities of oral synthetic retinoids: 
experimental findings and clinical experience. 
============================================================ 
Br J Dermatol 1983 Jul;109 Suppl 25:55-60 

Orfanos CE, Bauer R 
Oral retinoids obviously influence dermal components such as cutaneous 
capillaries and dermal inflammatory cells in addition to their well-known 
action on keratinizing epithelia. On this basis, they act as an 
anti-inflammatory drug. In particular, they reduce the elevated skin 
temperature, inhibit the motility of neutrophils and eosinophils and their 
migration into the epidermis, decrease DNA synthesis of human lymphocytes 
by blocking their response to lectins and stimulate Langerhans cells, 
monocytes and macrophages in various in vitro and in vivo models. These 
data indicate that oral retinoids may not only normalize disorders of 
keratinization but also exert distinct therapeutic effects on various skin 
diseases with dermal inflammatory involvement regardless of their 
particular aetiology. In some respects, retinoids resemble corticosteroids, 
acting as a modified hormone. Preliminary clinical experiences with oral 
retinoid treatment in skin diseases such as cutaneous disseminated LE, 
bullous pemphigoid, Duhring's disease, pemphigus, Behcet's disease and 
necrotizing vasculitis with eosinophilia support these data. Monotherapy or 
combined administration of oral retinoids with corticosteroids in low doses 
seems therapeutically beneficial in these disorders. 

============================================================ 
26.) Adult pityriasis rubra pilaris: a 10-year case series. 
============================================================ 
J Am Acad Dermatol 1997 Jun;36(6 Pt 1):959-64 

Clayton BD, Jorizzo JL, Hitchcock MG, Fleischer AB Jr, Williford PM, 
Feldman SR, White WL 
Department of Dermatology, Bowman Gray School of Medicine, Winston-Salem, 
NC 27157, USA. 

BACKGROUND: Pityriasis rubra pilaris (PRP) often has a devastating impact 
on the lives of patients. Descriptions of its histopathologic features are 
not uniform. Finding a successful therapy can be challenging. OBJECTIVE: 
Our purpose was to examine the histopathologic features and response of 
patients to our standard therapy of an oral retinoid and concomitant or 
later addition of low-dose weekly methotrexate. METHODS: A retrospective 
chart review was done on 24 patients with PRP seen from March 1986 to March 
1996. Biopsy specimens from 19 patients were reexamined. Telephone 
follow-up was conducted to determine maintenance of remission. RESULTS: All 
patients had the adult acquired form of PRP. Biopsy specimens from nine 
patients were characterized by prototypical findings of PRP, while the 
others included both typical and other features. Twenty-two patients were 
treated with either isotretinoin, 40 mg twice daily, or etretinate, 25 to 
75 mg/day. Six patients with more disabling involvement had low-dose weekly 
methotrexate ranging from 5 to 30 mg started concurrently. Five patients 
had weekly methotrexate added at a later time. Seventeen patients showed 
25% to 75% response after 16 weeks of therapy. All patients whose skin 
cleared maintained their remission. CONCLUSION: Initial oral retinoid plus 
concurrent or later low-dose weekly methotrexate resulted in 25% to 75% 
improvement of PRP in 17 of 24 patients after 16 weeks of therapy. Some of 
the atypical features seen in biopsy specimens emphasize the importance of 
clinical and histopathologic correlation in establishing the diagnosis. 

============================================================ 
27.) Isotretinoin treatment of pityriasis rubra pilaris. 
============================================================ 
J Am Acad Dermatol 1987 Feb;16(2 Pt 1):297-301 

Dicken CH 
Five patients with pityriasis rubra pilaris were treated with isotretinoin 
from September 1982 through 1985. Isotretinoin at an average dose of 1.16 
mg/kg/day for 16 to 24 weeks caused complete or almost complete clearing in 
four of the five patients. 

============================================================ 
28.) Phase I trial of retinoic acid and cis-platinum for advanced squamous 
cell cancer of the head and neck based on experimental evidence of drug 
synergism. 
============================================================ 
Otolaryngol Head Neck Surg 1998 May;118(5):597-602 

Weisman RA, Christen R, Los G, Jones V, Kerber C, Seagren S, Glassmeyer S, 
Orloff LA, Wong W, Kirmani S, Howell S 
Department of Surgery, University of California, San Diego, San Diego 
Veterans Administration Medical Center, USA. 

OBJECTIVE: Cis-platinum and 13-cis-retinoic acid have received much 
attention in the treatment of head and neck squamous cell cancer. Even 
though they have different mechanisms of action, little information is 
available on their interaction. This paper reviews experimental evidence 
for retinoic acid-cis-platinum synergy and presents toxicity data from 
patients with stage IV head and neck squamous cell cancer participating in 
a phase I trial combining 13-cis-retinoic acid and cis-platinum. METHODS: 
Patients were given 13-cis-retinoic acid orally daily for 7 days before and 
daily during high-dose (150 mg/m2 per week for 4 weeks) intraarterial 
cis-platinum treatment with concurrent radiation. Toxicity was scored with 
use of the cancer and leukemia group B scale. RESULTS: In the phase I 
clinical trial, 15 patients were treated to determine a maximum tolerated 
dosage for 13-cis-retinoic acid of 20 mg/day. Grade 4 hematologic toxicity 
was dose limiting in 3 of 8 patients treated with 40 mg/day and in 1 
patient treated with 60 mg/day. There were no deaths caused by toxicity; 12 
of the 15 patients received all four weekly doses and the remaining 3 
received three doses. Of 10 patients with fully evaluable data, all 
achieved a complete response at the primary site and 9 had a complete 
response in the neck. One patient had persistent neck disease after 
chemoradiation, and this tumor was removed with neck dissection. 
CONCLUSIONS: 13-Cis-retinoic acid and cis-platinum are strongly synergistic 
against head and neck squamous cell cancer in vitro. Pretreatment with 
retinoic acid results in stronger synergy than concurrent drug exposure 
alone. Preliminary clinical experience with combined retinoic acid and 
cis-platinum in a design that parallels the in vitro study indicates that 
toxicity is acceptable with 13-cis-retinoic acid dosages of 20 mg/day in a 
high-dose-intensity intraarterial chemoradiation regimen. 

============================================================ 
29.) Follicular mucinosis successfully treated with isotretinoin. 
============================================================ 
Eur J Dermatol 1999 Jan-Feb;9(1):22-4 

Guerriero C, De Simone C, Guidi B, Rotoli M, Venier A 
Department of Dermatology, Catholic University of Sacred Heart, Largo A. 
Gemelli, 8, 00168 Rome, Italy. 

We describe the case of a 33-year-old Caucasian male with follicular 
mucinosis successfully treated with isotretinoin. Follicular mucinosis is a 
primary idiopathic disease or a secondary, lymphoma-associated dermatosis. 
An effective standard therapy for this disease is unknown. In our case, 
isotretinoin led to a dramatic improvement of the skin lesions in about two 
weeks.To the best of our knowledge, the benefits of isotretinoin in the 
treatment of follicular mucinosis have never been reported previously. The 
efficacy of this drug could be mediated by a regulatory effect on the 
infiltrating cells and/or by a modulation of the target organ (skin) 
response to the infiltrating cells. 

============================================================ 
30.) Improvement of scleromyxedema associated with isotretinoin therapy. 
============================================================ 
J Am Acad Dermatol 1991 May;24(5 Pt 2):854-7 

Hisler BM, Savoy LB, Hashimoto K 
Dermatology Service, Veterans Administration Medical Center, Allen Park, MI 
48226. 

The treatment of scleromyxedema has been largely ineffective. We report 
improvement of scleromyxedema with myopathy after treatment with 
isotretinoin, 40 mg twice a day. We review other therapeutic modalities 
used for this disorder and discuss properties of isotretinoin that may have 
contributed to the favorable response. 

============================================================ 
31.) [Scleromyxedema therapy with isotretinoin]. 
============================================================ 
Z Hautkr 1988 Feb 15;63(2):137-8, 141 

Lominska-Lasota K, Rosen-Uzelac G, Reichl W, Bauer R 
Universitats-Hautklinik und Poliklinik, der Rheinischen 
Friedrich-Wilhelm-Universitat Bonn. 

We report on a 56-year-old male patient suffering from scleromyxedema, who 
was successfully treated with isotretinoin (13-cis retinoic acid, 
Roaccutan). After 10 months therapy, we observed considerable reduction of 
the cutaneous infiltration and the skin thickening; the papular eruptions 
had almost completely disappeared. The mobility of the joints, however, 
could only be slightly improved. 

============================================================ 
32.) Comparative study of systemic interferon alfa-2a with oral 
isotretinoin and oral isotretinoin alone in the treatment of recurrent 
condylomata accuminata. 
============================================================ 
Author 
Cardamakis EK; Kotoulas IG; Dimopoulos DP; Stathopoulos EN; Michopoulos JT; 
Tzingounis VA 
Address 
Department of Obstetrics and Gynecology, University of Patras, Rio-Patras, 
Greece. 
Source 
Arch Gynecol Obstet, 258(1):35-41 1996 
Abstract 
OBJECTIVES: We attempted to test the hypothesis that the combination of 
systemic interferon alfa-2a and oral isotretinoin is more effective than 
isotretinoin alone in the treatment of recurrent condylomata accuminata. 
STUDY DESIGN: Fifty seven women with recurrent condylomata accuminata were 
randomly assigned in two groups. Group A (n = 24) received isotretinoin 
alone (Roaccutan, Roche) 1 mg/kgr orally daily for 3 months or until a 
remission was achieved; Group B (n = 33) received Interferon alfa-2a 
(Roferon-A, Roche) 3 million units subcutaneously three times for 8 weeks 
plus isotretinoin 1 mg/Kg orally for 3 months or until a remission was 
achieved. RESULTS: There was no statistically significance in remission 
rates between the two groups (18/24 vs 28/33, p > 0.1). However the 
duration of treatment was statistically significantly shorter in Group B 
(1.9 vs 2.5 months, p < 0.01). Side effects were minimal. 
Language 

============================================================ 
33.) Treatment of condylomata acuminata with oral isotretinoin. 
============================================================ 
Author 
Tsambaos D; Georgiou S; Monastirli A; Sakkis T; Sagriotis A; Goerz G 
Address 
Department of Dermatology, University of Patras, Greece. 
Source 
J Urol, 158(5):1810-2 1997 Nov 
Abstract 
PURPOSE: The aim of our study was to evaluate the efficacy and safety of 
oral isotretinoin in the treatment of condylomata acuminata. MATERIALS AND 
METHODS: A total of 56 male patients with a history of condylomata 
acuminata refractory to at least 1 standard therapeutic regimen was treated 
orally with isotretinoin (1 mg./kg. daily) during a 3-month period. 
RESULTS: At the end of treatment 21 of the 53 evaluated patients (39.6%) 
had complete response, 7 (13.2%) had partial response and 25 (47.1%) had no 
response. A statistically significant inverse relationship was found 
between age and area of treated lesions and response to medication. Two 
complete responders (9.5%) revealed recurrence during the 1-year followup. 
CONCLUSIONS: Oral isotretinoin may be regarded as an effective, fairly well 
tolerated and noninvasive alternative form of therapy for immature and 
small condylomata acuminata. 

============================================================ 
34.) [Gilbert disease and isotretinoin] 
============================================================ 
Author 
Le Gal FA; Pauwels C 
Address 
Centre Hospitalier, Service de Dermatologie, Saint-Germain-en-Laye. 
Source 
Ann Dermatol Venereol, 124(6-7):463-6 1997 
Abstract 
INTRODUCTION: Because of the potential hepatotoxicity of retinoids, 
prescription of isotretinoin is always very carefully made in healthy 
subjects, and prohibited in case of concomitant hepatopathy. Gilbert's 
syndrome consists of chronic, mild, unconjugated hyperbilirubinemia. In 
this syndrome, isotretinoin has been reported twice to be perfectly 
tolerated, and once even beneficial. We report here a new case of good 
tolerance and even improvement of a Gilbert's syndrome during isotretinoin 
therapy. CASE REPORT: A 17-year-old man with Gilbert's syndrome presented 
with a nodulocystic acne. Topical agents had been inefficient, and cyclines 
bad tolerated. Thus isotretinoin has been gradually introduced, with a 
regular monitoring of the liver function. We observed a steady decrease of 
the bilirubinemia during the course of isotretinoin, and then a 
reappearance of hyperbilirubinemia as soon as posology was diminished and 
particularly after completion of isotretinoin therapy. DISCUSSION: A review 
of the literature finds only very few cases of hepatic injuries caused by 
isotretinoin, contrary to etretinate. Safety of isotretinoin in Gilbert's 
syndrome was first observed in 1984, but its beneficial effects have only 
recently been described by Wang et al., and we report here a similar case. 
Pharmacological mechanisms remain hypothetic. However, considering the 
prevalence of Gilbert's syndrome and its usual first expression during 
postpubertal period, it seems to us interesting for therapeutic practice to 
know that isotretinoin is not less safe in these patients. 

============================================================ 
35.) Zinc pretreatment inhibits isotretinoin teratogenicity and induces 
embryonic metallothionein in CD-1 mice. 
============================================================ 
J Nutr 1998 Jul;128(7):1239-46 

Blain D, Kubow S, Chan HM 
School of Dietetics and Human Nutrition, Macdonald Campus of McGill 
University, Ste. Anne de Bellevue, Quebec, Canada H9X 3V9. 

Isotretinoin (ITR), a teratogen in many species, is associated with 
increased oxidative stress. Metallothionein (MT) is an important tissue 
antioxidant whose concentrations are induced by zinc. To study the role of 
supplemental Zn as an inducer of embryonic MT, we injected pregnant CD-1 
mice subcutaneously with saline vehicle, or 20 or 40 mg/kg Zn on 
gestational day (GD) 6.5. After 48 h, embryonic MT concentrations increased 
in a dose-related manner (r = 0.64, P < 0.05) with Zn treatment. The 
possible protective role of Zn pretreatment against ITR teratogenicity was 
investigated in vivo and in vitro. CD-1 mice were pretreated with saline or 
Zn (20 and 40 mg/kg) on GD 8.5 and 9.5. ITR was administered to both groups 
of mice via three intragastric intubations of 100 mg ITR/kg at 4 h 
intervals on GD 10.5. On GD 18.5, Zn pre-treated mice demonstrated 
decreased ITR-mediated growth retardation, cleft palates and postpartum 
mortality. A reduction in embryonic MT concentrations was observed in mice 
exposed to ITR. Mouse embryos cultured on GD 8.5 with an addition of 15 
micromol/L Zn for 48 h had a sixfold greater MT concentration (688 microg/g 
protein) than controls. The Zn pretreatment of cultured embryos prevented 
malformations and lessened growth retardation caused by 24 h exposure to 17 
micromol/L ITR. These results suggest that Zn-mediated induction of MT in 
mouse embryos could protect against ITR teratogenicity. 

============================================================ 
36.) Negligible systemic absorption of topical isotretinoin cream: 
implications for teratogenicity. 
============================================================ 
Chen C; Jensen BK; Mistry G; Wyss R; Zultak M; Patel IH; Rakhit AK 
Department of Clinical Pharmacology, Hoffmann-La Roche, Inc., Nutley, 
New Jersey 07110, USA. 
J Clin Pharmacol (UNITED STATES) Apr 1997 37 (4) p279-84 ISSN: 0091- 
2700 
Language: ENGLISH 
Document Type: CLINICAL TRIAL; JOURNAL ARTICLE 
Journal Announcement: 9708 
Subfile: INDEX MEDICUS 
The objective of the study was to assess the extent of systemic exposure 
of retinoic acid metabolites after excessive application of 0.1% 
isotretinoin cream in patients with photodamaged skin. This was a single- 
center, open-label, noncomparative, multiple-dose study of isotretinoin 
cream. Eighteen female patients with photodamaged skin received a 10 g 
topical application of isotretinoin cream once daily to a surface area of 
approximately 2,300 cm2 for 42 days. The patients were not allowed to 
have high vitamin A-containing foods, vitamin A supplements, or 
concomitant medications during the entire study period. Plasma levels of 
four retinoic acids (isotretinoin, tretinoin, 4-oxo-isotretinoin, and 4- 
oxo-tretinoin) were evaluated after 42 days of isotretinoin application 
and compared with baseline (pretreatment) levels. The mean area under the 
curve (AUC) in plasma increased by 48% (+/-SE 9.2) and 77% (+/-13) from 
the 24-hour pretreatment baseline level for isotretinoin and 4-oxo- 
isotretinoin, respectively, after treatment with excessive amounts of 
isotretinoin cream, suggesting systemic absorption of isotretinoin cream. 
This increase in systemic exposure of retinoic acids was less than that 
reported earlier after the U.S. recommended daily allowance of 5,000 i.u. 
of vitamin A supplementation (isotretinoin 141 +/- 19% and 4-oxo- 
isotretinoin 171 +/- 27%). The minimal systemic availability of 
isotretinoin cream compared with the U.S. recommended daily allowance for 
vitamin A supplements provides reasonable evidence for lack of its 
potential teratogenic risk. 

============================================================ 
37.) Treatment of patients who have fibrodysplasia ossificans progressiva 
with isotretinoin. 
============================================================ 
Author 
Zasloff MA; Rocke DM; Crofford LJ; Hahn GV; Kaplan FS 
Address 
Human Genetics Branch, National Institute of Childhood Diseases, Bethesda, 
MD, USA. 
Source 
Clin Orthop, (346):121-9 1998 Jan 
Abstract 
Retinoids are a plausible family of therapeutic agents for fibrodysplasia 
ossificans progressiva due to their ability to inhibit differentiation of 
mesenchymal tissue into cartilage and bone. A prospective study was 
conducted to assess the efficacy of isotretinoin (13-cis-retinoic acid) in 
the prevention of heterotopic ossification in patients who had 
fibrodysplasia ossificans progressiva. Eleven anatomic regions were 
assessed in each of 21 patients by clinical examination, radiographs, and 
bone scans. An anatomic region was considered to be involved if there was 
clinical, radiographic, or radionuclide evidence of orthotopic or 
heterotopic ossification anywhere in the region. There were 143 involved 
anatomic regions and 88 uninvolved anatomic regions at the beginning of the 
study. Only one of the 88 anatomic regions that was completely uninvolved 
at the beginning of the study became involved during isotretinoin therapy. 
However, 16 of the 21 patients (76%) had major flare ups develop in 38 of 
143 (27%) previously involved anatomic regions while administered 
isotretinoin therapy. Isotretinoin at steady state doses of 1 to 2 mg/kg 
per day decreased the incidence of heterotopic ossification at uninvolved 
anatomic regions compared with an external control group, as long as the 
medication was started before the appearance of any orthotopic or 
heterotopic ossification in that anatomic region. The data did not allow 
the determination of whether isotretinoin was effective or detrimental in 
preventing disease flareups in regions that had even minimal orthotopic or 
heterotopic ossification at the time the therapy began. Extreme caution 
should be exercised when using this medication in patients who have 
fibrodysplasia ossificans progressiva. 

============================================================ 
38.) The cytostatic effect of 9-cis-retinoic acid, tretinoin, and 
isotretinoin on three different human bladder cancer cell lines in vitro. 
============================================================ 
Author 
Laaksovirta S; Rajala P; Nurmi M; Tammela TL; Laato M 
Address 
Division of Urology, Tampere University Hospital, Finland. 
Source 
Urol Res, 27(1):17-22 1999 
Abstract 
Retinoids have been shown to have activity in both preclinical and clinical 
bladder cancer studies but their exact role in its treatment and prevention 
remains obscure. In this study cytostatic activity of a novel 
9-cis-retinoic acid (9-cis-RA) was compared with two other retinoids: 
tretinoin and isotretinoin, in three different bladder cancer cell lines: 
RT4 (well differentiated), 5637 (moderately differentiated) and T24 (poorly 
differentiated). The three retinoids were incubated at concentrations of 
0.3, 3 and 30 microg/ml with bladder cancer cells in microtitre plates for 
3 and 6 days. The cytostatic effect was estimated by using luminometric 
measuring of ATP activity of viable cells in suspension. Compared with the 
older retinoids, tretinoin and isotretinoin, the highest concentration of 
9-cis-RA had a cytostatic efficacy in all three bladder cancer cell lines 
tested. A clear dose response relationship was observed in 
isotretinoin-treated cultures after 6 days and in all 9-cis-RA-treated 
cultures. Tretinoin was either ineffective or had a stimulating effect on 
poorly differentiated tumour cells. To conclude, isotretinoin and 9-cis-RA 
had a cytostatic effect on human bladder cancer cells in vitro. However, 
the possibility of stimulating cancer growth at small doses, at least with 
tretinoin, and toxicity at high doses must be considered when planning 
clinical trials. 

============================================================ 
39.) Chemotherapy for disseminated actinic keratoses with 5-fluorouracil 
and isotretinoin. 
============================================================ 
Author 
Sander CA; Pfeiffer C; Kligman AM; Plewig G 
Address 
Department of Dermatology, Ludwig-Maximilians-Universitaet, Munich, Germany. 
Source 
J Am Acad Dermatol, 36(2 Pt 1):236-8 1997 Feb 
Abstract 
BACKGROUND: Disseminated actinic keratoses are a therapeutic problem. 
OBJECTIVE: Our purpose was to evaluate the efficacy of a combination of 
topical 5-fluorouracil twice a day and 20 mg of oral isotretinoin daily for 
disseminated actinic keratoses. METHODS: Twenty-seven patients who had 
disseminated actinic keratoses (3 women, 24 men) were treated with 
5-fluorouracil (5%) twice a day applied to the photodamaged area bearing 
actinic keratoses along with oral isotretinoin, 20 mg daily. The median 
treatment time was 21 days. RESULTS: Actinic keratoses disappeared and 
signs of photodamaged skin improved in all patients. Side effects were 
burning and itching as well as painful erosions during the final stage of 
treatment. CONCLUSION: The combination of topical 5-fluorouracil and 
isotretinoin is highly effective in the treatment of disseminated actinic 
keratoses on photodamaged skin. 

============================================================ 
40.) A case of atrophoderma vermiculatum responding to isotretinoin. 
============================================================ 
Author 
Weightman W 
Address 
Department of Dermatology, Queen Elizabeth Hospital, Woodville, Australia. 
Source 
Clin Exp Dermatol, 23(2):89-91 1998 Mar 
Abstract 
Atrophoderma vermiculatum (AV) is a rare disorder leading to reticular or 
honeycomb scarring of the face and responding poorly to treatment. A case 
is now presented of the successful induction of remission in the 
inflammatory component of the disease following a prolonged course of 
isotretinoin; improvement was then maintained after cessation of the 
treatment. In severe cases of AV with significant scarring, a trial of 
isotretinoin therapy is thus worthwhile in an attempt to stop progression 
of the disease and improve its cosmetic appearance. 

============================================================ 
41.) Cutaneous sarcoidosis: complete remission after oral isotretinoin 
therapy. 
============================================================ 
Author 
Georgiou S; Monastirli A; Pasmatzi E; Tsambaos D 
Address 
Department of Dermatology, University of Patras, Rio-Patras, Greece. 
Source 
Acta Derm Venereol, 78(6):457-9 1998 Nov 
Abstract 
We report a 31-year-old female patient with cutaneous sarcoidosis, who 
showed a complete remission of her single system skin disease after an 
8-month therapy with oral isotretinoin (1 mg/kg/day). At 15-month 
follow-up, the patient still remained free of recurrence and visceral 
involvement. 

============================================================ 
42.) Isotretinoin for refractory lupus erythematosus. 
============================================================ 
J Am Acad Dermatol 1991 Jan;24(1):49-52 

Shornick JK, Formica N, Parke AL 
Division of Dermatology, University of Connecticut Health Center, Farmington. 

We describe six patients with cutaneous manifestations of lupus 
erythematosus who were treated with isotretinoin, 1 mg/kg/day. In each case 
the cutaneous lesions had proved resistant to systemic corticosteroids and 
antimalarial therapy. Treatment with isotretinoin resulted in rapid 
clinical improvement in all cases. Recurrences were similarly rapid when 
the drug was discontinued. Side effects were minimal and easily controlled 
by adjustments in dose or by the use of lubricants. 

============================================================ 
43.) [Use of oral isotretinoin in the treatment of cutaneous lupus 
erythematosus]. 
============================================================ 
G Ital Dermatol Venereol 1989 Jun;124(6):311-5 
[Article in Italian] 


Vena GA, Coviello C, Angelini G 
Twenty-four in- or out-patients (12 males and 12 females) with chronic 
cutaneous (CCLE) (n = 19) or subacute cutaneous (SCLE) (n = 5) lupus 
erythematosus have been treated with oral isotretinoin. The initial dose 
0.15 mg/kg/day was progressively increased to a maximum of 0.50 mg/kg/day; 
the total treatment period was 16 weeks. One female patient with SCLE 
stopped the therapy for sudden fever. None of the other known side effects 
induced interruption of treatment. In 20 subjects (86.9%) isotretinoin 
therapy was associated with clearing or improvement of clinical lesions and 
histopathologic changes. Best responses with isotretinoin therapy was seen 
in patients with CCLE. No changes were observed in the laboratory 
parameters before, during, and at the end of the study. In the light of 
these results, isotretinoin can be considered as an effective and 
well-tolerated drug in the treatment of cutaneous lupus erythematosus. 

============================================================ 
44.) Successful treatment of hypertrophic lupus erythematosus with 
isotretinoin. 
============================================================ 
J Am Acad Dermatol 1987 Aug;17(2 Pt 2):364-8 

Green SG, Piette WW 
A patient with systemic lupus erythematosus had the additional finding of 
hypertrophic lupus erythematosus. The lesions cleared with an 11-week 
course of isotretinoin alone. She has remained without recurrence for 9 
months. This is the first reported case of total resolution of hypertrophic 
lupus erythematosus with a short course of isotretinoin. 

============================================================ 
45.) Isotretinoin in the treatment of systemic sclerosis. 
============================================================ 
Br J Dermatol 1989 Sep;121(3):367-74 

Maurice PD, Bunker CB, Dowd PM 
Department of Dermatology, Middlesex Hospital, London, U.K. 

Thirteen patients with systemic sclerosis were treated with isotretinoin. 
Nine patients completed between 6 and 14 months of treatment and all showed 
an improvement in the cutaneous manifestations of their disease. The drug 
did not appear to benefit internal organs affected by the disease. Most 
patients experienced the well-recognized side-effects of retinoids, which 
in three cases necessitated withdrawal from the study within 3 months. 
Serum levels of type III procollagen aminopropeptide did not show a 
consistent decline during treatment, despite a clinical improvement. The 
mode of action of the reported therapeutic effect of isotretinoin in 
systemic sclerosis is unclear. There may be a preferential suppression of 
the synthesis of type I collagen, or the drug may be acting by an unrelated 
mechanism. 

============================================================ 
46.) Isotretinoin and lung function in systemic sclerosis. 
============================================================ 
Clin Exp Dermatol 1991 Jan;16(1):11-3 

Bunker CB, Maurice PD, Little S, Johnson NM, Dowd PM 
Department of Dermatology, University College and Middlesex School of 
Medicine, Middlesex Hospital, London, UK. 

During an open prospective study of the synthetic retinoid isotretinoin in 
ten patients with systemic sclerosis, one patient developed an eosinophilic 
pleural effusion and two patients were noticed to have asymptomatic 
deterioration in pulmonary function tests. The pulmonary function of all 
treated patients was then compared retrospectively with a similar control 
group of patients not treated with isotretinoin. There was a significantly 
greater decrease in the 1-s forced expiratory volume and transfer 
coefficient in the patients with systemic sclerosis being treated with 
isotretinoin in comparison to the untreated control patients. Studies of 
lung function in patients treated with isotretinoin for other indications 
are required. 

============================================================ 
47.) [Keratosis follicularis spinulosa decalvans. Therapy with isotretinoin 
and etretinate in the inflammatory stage]. 
============================================================ 
Hautarzt 1993 Aug;44(8):529-34 

Richard G, Harth W 
Haut- und Poliklinik, Medizinischen Hochschule Erfurt. 

Keratosis follicularis spinulosa decalvans (KFSD) is a rare X-linked 
disorder of keratinization of the hair follicle associated with corneal 
dystrophy. The clinical picture is characterized by solid follicular 
hyperkeratosis, especially on the exposed skin, sparse eyebrows/eyelashes, 
follicular scaling and scarring alopecia of the scalp, dry skin and ocular 
symptoms with keratitis and photophobia. We describe the three stages of 
the disease: onset, inflammation and partial remission and the treatment 
appropriate in each. Two patients in the inflammatory stage of KFSD, with 
recurrent deep, fibrosing folliculitis and perifolliculitis followed by 
spreading and scarring alopecia on the scalp, responded to oral therapy 
with retinoids. In both cases there was a distinct and lasting remission of 
the inflammation and stabilization of the spreading alopecia after 
treatment with etretinate (Tigason), up to 0.8 mg/kg body weight, or 
isotretinoin (Roaccutan), 0.5 mg/kg body weight, for 12 weeks. The 
follicular spinulous hyperkeratosis became softer, but persisted. Thus, 
oral therapy with retinoids appears helpful in the inflammatory stage of 
KFSD, even though there is little improvement in the follicular 
hyperkeratosis. 

============================================================ 
48.) Treatment of oral erosive lichen planus with systemic isotretinoin. 
============================================================ 
Oral Surg Oral Med Oral Pathol 1986 Oct;62(4):393-6 
Camisa C, Allen CM 
Six patients with symptomatic oral erosive lichen planus were treated with 
systemic isotretinoin (10 to 60 mg daily) for 8 weeks. Five (83%) showed 
subjective and objective improvement at completion of therapy, but the 
improvement was slight. Relapse occurred in four patients within 2 months 
after the drug was stopped; one was lost to follow-up. Because of the 
minimal improvement and adverse side effects, no patient wished to be 
re-treated with isotretinoin. 

============================================================ 
49.) Topical application of isotretinoin gel improves oral lichen planus. A 
============================================================ 
double-blind study. 
Arch Dermatol 1986 May;122(5):534-6 

Giustina TA, Stewart JC, Ellis CN, Regezi JA, Annesley T, Woo TY, Voorhees JJ 
In a double-blind study, 20 patients with oral lichen planus were treated 
twice daily with 0.1% isotretinoin gel or the vehicle alone for two months. 
Subsequently, patients who used the placebo received the active preparation 
for another two months. Patients treated with the active medication 
displayed significantly greater improvement than patients receiving the 
placebo. Patients who were treated initially with the placebo showed 
statistically significant improvement after receiving the topical 
isotretinoin treatment for two months. Side effects from using the gel were 
primarily a transient burning sensation or irritation on initial application. 

============================================================ 
50.) Systemic isotretinoin treatment of oral and cutaneous lichen planus. 
============================================================ 
Cutis 1985 Apr;35(4):385-6, 390-1, 393 

Woo TY 
Lichen planus of the skin and mucous membranes may be disabling. Severe 
pruritus or bullous lesions may be incapacitating when they occur while 
erosive oral lesions may be extremely painful. Various treatment modalities 
have been attempted including corticosteroids (parenteral, intralesional, 
and topical) and photochemotherapy. Recent successful therapeutic trials of 
topical retinoic acid and oral etretinate have been completed. Two patients 
with cutaneous and severe erosive oral lichen planus unresponsive to 
conventional therapies responded to a trial of oral isotretinoin with 
prompt and successful remission of cutaneous and oral lesions. This 
suggests that systemic isotretinoin may have a unique position in the 
treatment of mucous membrane lichen planus that is refractory to 
conventional therapies. 

============================================================ 
51.) Variant of keratoderma hereditaria mutilans (Vohwinkel's syndrome). 
Treatment with orally administered isotretinoin. 
============================================================ 
Arch Dermatol 1984 Oct;120(10):1323-8 

Camisa C, Rossana C 
Keratoderma hereditaria mutilans (KHM), or Vohwinkel's syndrome, is a rare 
genodermatosis consisting of hyperkeratosis of the palms and soles with a 
characteristic "honeycomb" appearance, keratotic structures taking the 
shape of a starfish and/or knuckle pads on the dorsal surfaces of the 
hands, and constricting bands (pseudoainhum) encircling digits of the hands 
and feet. We describe three cases of a variant of KHM with an associated 
ichthyosiform dermatosis in a pedigree consisting of 19 affected 
individuals through six generations. An autosomal dominant inheritance 
pattern for KHM was confirmed. One of the patients was successfully treated 
with isotretinoin, 0.6 mg/kg/day orally. We offer five hypothetical genetic 
models to account for the simultaneous expression of palmar-plantar 
keratoderma and ichthyosiform dermatosis. 

============================================================ 
52.) Lupus miliaris disseminatus faciei: efficacy of isotretinoin. 
============================================================ 
J Am Acad Dermatol 1987 Jun;16(6):1271-2 
Berbis P, Privat Y 
Publication Types: 
Letter 
============================================================ 
============================================================ 
53.) Epidermolysis bullosa simplex responding to isotretinoin. 
============================================================ 
Arch Dermatol 1988 Sep;124(9):1445-6 

Andreano JM, Tomecki KJ 
Publication Types: 
Letter 
============================================================ 
============================================================ 
54.) Remission after 13-cis retinoic acid in thrombotic thrombocytopenic 
purpura. 
============================================================ 
Lancet 1998 Aug 8;352(9126):454-5 

Raife TJ, McArthur J, Peters C, Kisker CT, Lentz SR 
Publication Types: 
Letter 
============================================================ 
LO MALO/ THE BAD 
============================================================ 
55.) [Acne, hyperandrogenism and oral isotretinoin resistance. 23 cases. 
Therapeutic implications] 
============================================================ 
Author 
Lehucher-Ceyrac D; Chaspoux C; Weber MJ; Morel P; Vexiau P 
Address 
Service Dermatologie, H^opital Saint-Louis, Paris. 
Source 
Ann Dermatol Venereol, 124(10):692-5 1997 
Abstract 
BACKGROUND: We earlier demonstrated that oral isotretinoin can be 
associated with hyperandrogenism in women with acne. The aim of this study 
was to evaluate the causal relationships of the different etiologies in 
case of unsuccessful treatment. PATIENTS AND METHODS: The study group 
included 120 patients with late-onset acne resistant to different treatment 
and signs of hyperandrogenism. A complete hormone work-up was obtained in 
all patients. There was a group of 23 patients who failed to respond to 
isotretinoin and 97 patients in the control group. Unsuccessful treatment 
was defined as persistance of grade 2 lesions after a mean cumulative dose 
of 166 mg/kg isotretinoin. RESULTS: In the non-responders to isotretinoin, 
hyperandrogenism was observed in 22 out of 23 cases: pituitary (n = 2), 
adrenal (n = 5), ovarian (n = 13), peripheral (n = 2). In the control 
group, hyperandrogenism was found in 89 out of 97 patients: pituitary (n = 
6), adrenal (n = 45), ovarian (n = 33), peripheral (n = 5). The 
distribution of two etiologies, ovary and adrenal, demonstrated a 
significant difference between isotretinoin non-responders and controls, 
the former having a higher frequency of ovarian hyperandrogenism. 
DISCUSSION: These findings confirm that untreated hyperandrogenism, 
particularly ovarian hyperandrogenism, is a source of unsuccessful 
treatment with oral isotretinoin. 

============================================================ 
56.) Predictive factors for failure of isotretinoin treatment in acne 
patients: 
results from a cohort of 237 patients. 
============================================================ 
Author 
Lehucher-Ceyrac D; de La Salmoni`ere P; Chastang C; Morel P 
Address 
Service de Dermatologie, H^opital Saint-Louis, Paris, France. 
Source 
Dermatology, 198(3):278-83 1999 
Abstract 
BACKGROUND: The efficacy of oral isotretinoin in acne has been established, 
though the role of the mean daily dose (MDD) is still unclear. OBJECTIVE: 
To determine the predictive factors of resistance to oral isotretinoin and 
the role of the MDD of isotretinoin on relapse of acne while taking into 
account patient characteristics and the total cumulative dose (TCD). 
METHODS: Two hundred and thirty-seven patients treated with oral 
isotretinoin for the first time were enrolled by a single dermatologist. 
Patients with closed comedonal acne and with hyperandrogenism received 
adequate therapy prior to isotretinoin. RESULTS: Closed comedonal acne was 
the only predictive factor of resistance to isotretinoin with an adjusted 
OR = 2.7 (95% CI: 1.0-7.3). The estimated rates of relapse at 1, 3 and 5 
years were 14, 40 and 48%, respectively. Age and grade of facial acne were 
the only predictive factors for relapse with adjusted relative risks of 0.6 
(95% CI: 0.4-0.8) for age >/= 20 and 1.5 (95% CI: 1.0-2.2) for grade > 3. 
CONCLUSION: MDD, TCD, closed comedonal acne and hyperandrogenism that have 
been adequately treated prior to isotretinoin treatment had no prognostic 
value for relapse. 

============================================================ 
57.) [Aggravation of acne by isotretinoin. 6 cases, predictive factors] 
============================================================ 
Author 
Lehucher Ceyrac D; Chaspoux C; Sulimovic L; Morel P; Lefrancq H 
Address 
Service Dermatologie, H^opital Saint-Louis, Paris. 
Source 
Ann Dermatol Venereol, 125(8):496-9 1998 Aug 
Abstract 
OBJECTIVE: Acne flare-ups are frequent in the early phase of isotretinoin 
treatment. Severity varies from one patient to another. Clinical factors 
favoring a potentially severe course were assessed on the basis of 6 cases. 
CASE REPORTS: Six male patients, mean age 16.5 years, with inflammatory 
acne with a major retentional component were studied. Isotretinoin 
administered at a daily dose 0.5 mg/kg led to explosive development of 
massive nodulocystic lesions or pyogenic granulomas within two months. The 
lesions healed at withdrawal of isotretinoin and administration of 
antibiotics and antiinflammatory drugs. There was important scar sequellae. 
DISCUSSION: Four concomitant factors were identified which contribute to 
the development of acne flare-ups: sex (male), young age, retentional form 
of acne and daily isotretinoin dose 0.5 mg/kg. 
Language 

============================================================ 
58.) Acne fulminans and erythema nodosum during isotretinoin therapy 
responding 
to dapsone. 
============================================================ 
Author 
Tan BB; Lear JT; Smith AG 
Address 
Department of Dermatology, Central Outpatients, Stoke-on-Trent, UK. 
Source 
Clin Exp Dermatol, 22(1):26-7 1997 Jan 
Abstract 
Acne vulgaris is very common, 85% of teenagers being affected at any one 
time. In most cases, the disease is mild and patients do not present to the 
dermatologist. Most are instead treated with over-the-counter products and 
conventional treatment such as peeling agents or topical and systemic 
antibiotics. Isotretinoin has revolutionized the treatment of severe acne 
unresponsive to oral antibiotics. Explosive and very severe acne such as 
pyoderma faciale, acne conglobata and acne fulminans are rare, the features 
that distinguish acne fulminans from the other conditions being systemic 
upset with fever, joint pain, malaise and leucocytosis, while there have 
been two reports of the condition associated with erythema nodosum. The 
recommended treatment for acne fulminans is a combination of oral steroids 
and systemic antibiotics, isotretinoin probably not being the treatment of 
choice. We now report a patient who developed acne fulminans and erythema 
nodosum within 3 weeks of starting isotretinoin and then responded to 
dapsone without oral steroids. 

============================================================ 
59.) [Muscular damage during isotretinoin treatment] 
============================================================ 
Author 
Heudes AM; Laroche L 
Address 
Unit&acute;e d'Immuno-Dermatologie, Universit&acute;e de Paris XIII, H^opital Avicenne, 
Bobigny. 
Source 
Ann Dermatol Venereol, 125(2):94-7 1998 Feb 
Abstract 
BACKGROUND: The effect of isotretinoin on muscle is considered to be 
uncommon and benign. We analyzed the files of all our patients given 
isotretinoin over a 5-year period and determined the incidence and gravity 
of its effect on muscles. MATERIALS AND METHODS: Sixty treatments with 
isotretinoin were studied. Myalgia and elevated CPK observed at the 
pretherapeutic consultation and each month or 2 months thereafter were 
recorded. RESULTS: Muscle symptoms were noted in 60 p. 100 of the cases: 
myalgia in 51 p. 100 and elevated CPK in 41 p. 100. In this group, male sex 
(H/F = 2.6) and sports activities (70 p. 100) were found more often. In 5 
patients, CPK level was 5 times the normal, defining rhabdomyolysis. One 
patient interrupted treatment because of persistently high CPK levels. 
DISCUSSION: Myalgia and elevated CPK signal skeletal muscle involvement. 
These signs were more frequent in our series than in reports in the 
literature, probably because we systematically looked for them. Besides use 
of isotretinoin, one case of viral infection and sports activities, no 
other explanatory cause could be found. Isotretinoin could have a 
potentializing effect on other myotoxicity inducers (drugs, infection, 
fever, muscular exertion...). The benign nature of the muscle effect 
appears to be validated although there were some patients who had 
persistent and/or severe signs. 

============================================================ 
60.) [Lung disease induced by isotretinoin] 
============================================================ 
TO: Pneumopathie induite par l'isotretinoine. 
AU: Oliviero-G; Constans-P; Caby-I; De-Rohan-Chabot-P; Lacherade-JC 
AD: Service de Pneumologie et Medecine Interne, CHG Longjumeau. 
SO: Rev-Mal-Respir. 1995; 12(6): 631-3 
ISSN: 0761-8425 
PY: 1995 
LA: FRENCH; NON-ENGLISH 
CP: FRANCE 
AB: A young man without any past history of note had taken isotretinoin for 
disfiguring acne before the summer season. He presented with a severe 
bilateral pneumonia, associated with dyspnoea two months after the start of 
treatment. On the pulmonary radiography there was a bilateral ground glass 
appearance which was worse on the right. The elevated level of eosinophils 
(54% in 564,000 cells/ml) in the alveolar lavage lead to a diagnosis of 
allergic pneumonia. The rapidly favourable outcome following the cessation 
of the medication and with the addition of corticosteroids seemed to us a 
supplementary argument in favour of a diagnosis of eosinophilic pneumonia, 
due to isotretinoin which seemed the primary initiating factor. 

============================================================ 
61.) Vestibular dysfunction in a child with embryonic exposure to accutane. 
============================================================ 
AU: Westerman-ST; Gilbert-LM; Schondel-L 
AD: Hahnemann Medical College, Philadelphia, Pennsylvania, USA. 
SO: Am-J-Otol. 1994 May; 15(3): 400-3 
ISSN: 0192-9763 
PY: 1994 
LA: ENGLISH 
CP: UNITED-STATES 
AB: Children with a history of embryonic exposure to Accutane 
(isotretinoin) are at great risk for major physical malformations, brain 
malformations, and decreased intelligence. A case is presented of a 4-year 
7-month-old black male with a history of embryonic exposure to Accutane who 
was born with embryopathy that includes bilateral major ear deformities. 
The child has a significant bilateral conductive hearing loss, and, in 
addition, a left sided sensorineural loss. Vestibular function testing 
revealed evidence of peripheral and central vestibular dysfunction. A 
course of diphenhydramine hydrochloride and Donnatal (phenobarbital, 
hyoscyamine sulfate, atropine sulfate, and scopolamine hydrobromide) 
significantly alleviated the symptoms of vestibular dysfunction. Otologic 
management of these children should include clinical documentation of the 
external deformities, evaluation of cochlear function, and early auditory 
habilitation. Vestibular function should also be evaluated in all children 
with a history of embryonic exposure to isotretinoin. 

============================================================ 
62.) Extraspinal enthesopathy caused by isotretinoin therapy. 
============================================================ 
J Manipulative Physiol Ther 1999 Jul-Aug;22(6):417-20 

Brandt JR, Mick TJ 
Department of Radiology, Northwestern College of Chiropractic, Bloomington, 
MN 55431-1599, USA. 

OBJECTIVE: To discuss a case of diffuse peripheral enthesopathy in a 
patient previously treated with long-term isotretinoin (Accutane) for 
severe acne. CLINICAL FEATURES: A 47-year old man with 1 month history of 
moderate neck and right upper extremity pain, with hypoesthesia of the 
right second and third fingers. Palpable bony prominences around multiple 
superficial joints were noted on physical examination, raising the initial 
question of osteochondromatosis. Multiple active acne pustules were noted. 
A limited skeletal survey demonstrated diffuse peripheral enthesophyte 
formation and hyperostoses, resembling those of diffuse idiopathic skeletal 
hyperostosis, but without accompanying spinal changes. A history of 
long-term Accutane therapy was then elicited. INTERVENTION AND OUTCOME: The 
enthesopathy was believed to represent an asymptomatic, longstanding, 
iatrogenically induced abnormality. No specific therapy or follow-up was 
indicated. The patient had discontinued use of Accutane years ago. Cervical 
symptoms improved with four sessions of cervical traction and nonsteroidal 
anti-inflammatory medications, but upper extremity symptoms were 
refractory. CONCLUSION: Accutane-induced enthesopathy should be considered 
in individuals with correlating radiologic and clinical features and 
history of retinoic acid therapy for acne. This should be a diagnosis by 
exclusion, after eliminating other potential causes of peripheral 
enthesopathy, particularly diffuse idiopathic skeletal hyperostosis, 
seronegative spondylarthropathy, and fluorosis. 

============================================================ 
63.) Generalized metaphyseal modification with cone-shaped epiphyses 
following long-term administration of 13-cis-retinoic acid. 
============================================================ 
Nishimura G; Mugishima H; Hirao J; Yamato M 
Department of Radiology, Dokkyo University School of Medicine, Tochigi- 
ken, Japan. 
Eur J Pediatr (GERMANY) Jun 1997 156 (6) p432-5 ISSN: 0340-6199 
Language: ENGLISH 
Document Type: JOURNAL ARTICLE 
Journal Announcement: 9710 
Subfile: INDEX MEDICUS 
We report on a 6-year-old girl with short stature which developed 
following the administration of 13-cis-retinoic acid (a synthetic 
derivative of vitamin A or retinoid) for 40 months as adjunct chemotherapy 
for neuroblastoma. Radiographic examination suggested osteophyte 
formation in the cervical spine, which is the most common skeletal 
manifestation of retinoid toxicity [10, 11]. In addition, severe 
metaphyseal cupping with a cone-shaped epiphysis primarily affecting 
rapidly growing long bones was found, which represented impaired 
enchondral ossification. This epi-metaphyseal alteration, though 
unusually severe, was reminiscent of the premature epiphyseal closure 
which has been described as an adverse effect of 13-cis-retinoic acid [10- 
12]. Other minor skeletal changes included posterior scalloping of the 
vertebral bodies and increased interpediculate distances, which were 
related to a widened spinal canal found on CT. A literature search 
disclosed several primary skeletal dysplasias with superficial 
radiological similarities to those of the present patient. However, these 
entities showed significant clinical and radiological differences from our 
patient. CONCLUSION: The precise cause of the generalized skeletal 
alteration in the present patient remained unknown, but it conceivably 
resulted from the administration of 13-cis-retinoic acid. 

============================================================ 
64.) Retinoid-induced ossification of the posterior longitudinal ligament. 
============================================================ 
Skeletal Radiol 1985;14(3):191-3 

Pennes DR, Martel W, Ellis CN 
Vitamin A and its synthetic congeners are known to produce a variety of 
skeletal abnormalities in patients on prolonged treatment with these 
medications. Two patients are described who developed posterior 
longitudinal ligament ossification following treatment with the synthetic 
retinoid 13-cis-retinoic acid. In both cases, this finding became apparent 
after other retinoid-induced skeletal abnormalities were observed and was 
less marked than the ossification of the anterior longitudinal ligament. 
Although spinal cord compression did not occur in our patients, patients on 
long-term retinoid therapy should be carefully observed for this 
complication. 

============================================================ 
65.) Isotretinoin-induced vasculitis imitating polyarteritis nodosa, with 
perinuclear antineutrophil cytoplasmic antibody in titers correlated with 
clinical symptoms. 
============================================================ 
Chochrad D; Langhendries JP; Stolear JC; Godin J 
Internal Medicine Department, Tournai Medical and Surgical Institute, 
Belgium. 
Rev Rhum Engl Ed (FRANCE) Feb 1997 64 (2) p129-31 ISSN: 0035-2659 
Language: ENGLISH 
Document Type: JOURNAL ARTICLE 
Journal Announcement: 9708 
Subfile: INDEX MEDICUS 
The adverse effects of retinoids on bones and joints are being 
increasingly documented. A case is reported in which isotretinoin was 
considered responsible for polyarteritis-like vasculitis. Perinuclear 
antineutrophil cytoplasmic antibodies were present in titers that 
correlated with clinical and laboratory test abnormalities. 

============================================================ 
66.) Arthropathy associated with cystic acne, hidradenitis suppurativa, and 
perifolliculitis capitis abscedens et suffodiens: treatment with isotretinoin. 
============================================================ 
Cutis 1999 Aug;64(2):87-90 

Libow LF, Friar DA 
Armed Forces Institute of Pathology, Dermatopathology Division, Washington, 
DC 20306-6000, USA. 

A patient with arthropathy associated with cystic acne, hidradenitis 
suppurativa, and perifolliculitis capitis abscedens et suffodiens who 
showed a dramatic response to isotretinoin is described. This, to our 
knowledge, is the first report documenting effective treatment of this 
condition, whose nosologic position with respect to other 
spondyloarthropathies associated with cutaneous disease is considered. 

============================================================ 
67.) [Acne in the male resistant to isotretinoin and responsibility of 
androgens: 9 cases, therapeutic implications (see comments)] 
============================================================ 
Author 
Chaspoux C; Lehucher-Ceyrac D; Morel P; Lefrancq H; Boudou P; Fiet J; 
Vexiau P 
Address 
Service d'Endocrinologie, H^opital Saint-Louis, Paris. 
Source 
Ann Dermatol Venereol, 126(1):17-9 1999 Jan 
Abstract 
INTRODUCTION: Treatment failures with isotretinoin in female patients are 
frequently related to endocrinological dysfunctions. Such a concept has 
never been discussed in male patients. CASE REPORTS: An extensive 
endocrinological work-up has been performed in nine male patients who 
presented with an acne refractory to conventional treatment and to 
isotretinoin. Adrenal dysfunction was found in four patients and isolated 
5-alpha reductase hyperactivity in 2 cases. Three work-ups were normal. A 
suppressive treatment in three patients with adrenal dysfunction provided 
immediate efficacy. COMMENTS: These results would provide insight into the 
mechanism of refractory acne in men. 

============================================================ 
68.) Ocular side effects of accutane therapy. 
============================================================ 
Lens Eye Toxic Res 1992;9(3-4):429-38 

Lerman S 
The recent interest in treating acne with one of the retinoid drugs has 
been accompanied by a wide variety of ocular side effects involving the 
eyelids, cornea, lens, optic nerve and retina. In one group of patients 
being evaluated for possible efficacy of a retinoic acid analogue in 
treating psoriasis, several patients complained of difficulty driving at 
night due to decreased dark adaptation which we were able to document. 
Fortunately, most of the above side effects tend to disappear within months 
after the drug is discontinued. However, we have recently seen two cases of 
dry eye syndrome associated with Accutane therapy that have persisted for 
more than two years. In addition, scattered reports have appeared regarding 
cataracts in young patients (teens to early 40's) which developed during, 
and/or after Accutane treatment. We have examined lens matter derived from 
two such patients who had extracapsular cataract extractions. Their lens 
proteins showed an elevation in UV absorptivity (between 330-390 nm) 
compared with matched control material (derived from Eye Bank specimens) 
and HPLC analyses demonstrated an abnormal peak in their profiles which was 
similar to one present in control samples incubated with retinoic acid and 
was not present in lens protein samples derived from cataracts not 
associated with Accutance therapy. These observations demonstrate that some 
of the Accutane induced ocular side affects are not reversible when the 
drug is stopped, and patients on such therapy should be carefully monitored. 

============================================================ 
69.) Isotretinoin and curly hair. 
============================================================ 
Clin Exp Dermatol 1990 Mar;15(2):143-5 

Bunker CB, Maurice PD, Dowd PM 
Department of Dermatology, University College and Middlesex School of 
Medicine, Middlesex Hospital, London, UK. 

A 46-year-old woman with systemic sclerosis was treated with isotretinoin 
for 1 year. She obtained considerable benefit and experienced only minor 
side-effects from the drug, comparable to those familiar to dermatologists 
in the treatment of acne. However, she noticed that her hair became 
pronouncedly more curly during treatment. 

============================================================ 
70.) The effect of isotretinoin on biotinidase activity. 
============================================================ 
Skin Pharmacol Appl Skin Physiol 1999 Jan-Apr;12(1-2):28-33 

Schulpis KH, Georgala S, Papakonstantinou ED, Michas T, Karikas GA 
Institute of Child Health, Aghia Sophia Children's Hospital, Athens, Greece. 

BACKGROUND: Among the reaction and effects of isotretinoin, mucocutaneous 
reactions, xerosis and erythema of the skin as well as elevation of liver 
enzymes and lipids except high density lipoprotein have been reported. 
OBJECTIVE: Since biotinidase is mainly produced in the liver and partial 
biotinidase deficiency causes dermatological manifestations, seborrheic 
dermatitis, alopecia etc., isotretinoin side effects in relation to 
biotinidase activity were studied. METHODS: Forty-two (n = 42) patients 
with severe cystic acne had liver function tests, lipid estimations, serum 
biotin as well as biotinidase activity evaluations before (value 1) and on 
the 30th day (value 2) of treatment with isotretinoin monotherapy 
(Roaccutane 0.5 mg/kg/24 h). The same laboratory tests were evaluated in 50 
controls only once. Moreover, the effect of isotretinoin on a known plasma 
biotinidase activity was evaluated after incubation in vitro with various 
concentrations of the drug. RESULTS: A statistically significant elevation 
of liver enzymes and lipids, except high density lipoprotein, was observed 
at the end of this study. On the contrary, biotinidase activity was found 
to be significantly decreased as compared to the initial values (value 1 = 
4.70 +/- 0.89 nmol/min/l, value 2 = 2.50 +/- 0.8 nmol/min/l, p < 0.001) and 
to controls (5.2 +/- 0.9 nmol/min/l vs. value 2 = 2.50 +/- 0.8 nmol/min/l, 
p < 0.001). Additionally, biotin levels showed no significant alterations 
and the in vitro incubation of the enzyme with various concentrations of 
the drug exhibited no effect on its activity. CONCLUSION: It is suggested 
that isotretinoin isomers-metabolites act in the liver, resulting in low 
biotinidase activity. 

============================================================ 
71.) Failure of isotretinoin in Kaposi's sarcoma. 
============================================================ 
Lancet 1984 Sep 15;2(8403):641 

Ziegler JL, Volberding PA, Itri LM 
Publication Types: 
Letter 
============================================================ 
LO FEO / THE UGLY 
============================================================ 
============================================================ 
72.) Suicide in dermatological patients. 
============================================================ 
Br J Dermatol 1997 Aug;137(2):246-50 

Cotterill JA, Cunliffe WJ 
Lasercare Clinics Ltd, Harrogate, U.K. 

Sixteen patients, seven men and nine women, who committed suicide after 
presenting with dermatological problems to two dermatologists, are 
described. Most of the patients had either a body image disorder 
(dysmorphophobia) or acne. In addition, patients with long-standing and 
debilitating skin disease may become depressed enough to commit suicide and 
there is always an attendant risk of suicide in patients with established, 
severe psychiatric problems, who are referred to dermatologists with 
concurrent skin disorders. It is important to recognize that patients with 
dermatological non-disease, and particularly women with facial complaints, 
may be extremely depressed and at risk of suicide. Facial scarring, 
particularly in men, may be an 'at risk' factor for suicide, emphasizing 
the positive early therapeutic role of isotretinoin. Funding problems in 
regard to provision of this drug could have potentially fatal consequences. 
The provision of a liaison clinic within a dermatology department may have 
an important role in managing patients thought to be at risk of suicide. 

============================================================ 
73.) Young women taking isotretinoin still conceive. Role of physicians in 
preventing disaster. 
============================================================ 
Can Fam Physician 1999 Feb;45:289-92 

Atanackovic G, Koren G 
University of Toronto. 

QUESTION: One of my adolescent patients was prescribed isotretinoin for 
severe acne by a dermatologist. I was shocked to discover she does not use 
any means of contraception. The dermatologist insists he told her about the 
need for contraception. How can we do better? ANSWER: Clearly this 
dermatologist, like many of his colleagues, does not comply with the 
Pregnancy Prevention Program. Until physicians become more aware of this 
program, babies will continue to be born with embryopathy due to 
isotretinoin. 

============================================================ 
74.) [Isotretinoin (Roaccutane) in women of childbearing age: failure of 
following prescription guidelines] 
============================================================ 
Author 
Autret E; Radal M; Jonville-B&acute;era AP; Goehrs JM 
Address 
Service de Pharmacologie Clinique, H^opital Bretonneau, Tours. 
Source 
Ann Dermatol Venereol, 124(8):518-22 1997 
Abstract 
BACKGROUND: Despite prominent warnings, pregnancies continue to be reported 
in women exposed to isotretinoin. PATIENTS AND METHODS: We report results 
of the analysis of 318 questions asked to pharacovigilance structures in 
France from 1987 to 1995 because of an exposition to isotretinoin during 
the risk period and of a prospective inquiry concerning isotretinoin 
prescription in women conducted among pharmacists. RESULTS: These 318 
pregnancies began during the month after Roaccutane withdrawal (n = 104, 33 
p. 100), during Roaccutane treatment (n = 163, 51 p. 100) or before 
Roaccutane treatment (n = 51, 16 p. 100). Of the 267 women with pregnancies 
conceived during treatment with isotretinoin (n = 104) or during the month 
after its discontinuation (n = 163), contraception was not prescribed in 28 
(15 p. 100) or prescribed but with poor compliance in 109 (60 p. 100). 
Pregnancy was terminated voluntarily in 199 women (81 p. 100). In the 173 
women who were interviewed in pharmacies, 49 (28 p. 100) did not use 
contraception and among them contraception was prescribed in only 59 p. 
100. Only 14 p. 100 had received full information about isotretinoin and 
pregnancy. The teratogenic effects of isotretinoin were known by 98 p. 100 
of the women and the need of contraception during treatment and for one 
month after discontinuation by 70 p. 100. DISCUSSION: Insufficient 
compliance with warnings is the main reason for pregnancies in women 
receiving isotretinoin therapy. A pregnancy prevention program is needed 
before prescription to ensure comprehension and to obtain informed consent 
of patients. 

============================================================ 
75.) Topical application of 13-cis-retinoic acid in the treatment of 
chronic plaque psoriasis. 
============================================================ 
Clin Exp Dermatol 1992 Jan;17(1):9-12 

Bischoff R, De Jong EM, Rulo HF, Sendagorta E, Czarnetzki BM, Van de 
Kerkhof PC 
Department of Dermatology, University Hospital Nijmegen, The Netherlands. 

Topical retinoids are of potential value in the treatment of psoriasis. The 
aim of the present study was to find out whether topical application of 
13-cis-retinoic acid (13-cis-RA) has an antipsoriatic effect. Nine patients 
participated in the investigation. In each patient, two comparable 
psoriatic lesions (5 x 5 cm or more) were selected for treatment with 
either 13-cis-RA in a 0.1% cream base or with the vehicle only (placebo), 
using a double-blind approach. The investigation was a left-right 
within-subject comparison. The lesions were recorded for clinical scores 4 
weeks before and after the investigation. Punch biopsies were taken from 
eight patients before and after treatment and examined using 
immunohistochemical methods to assess epidermal proliferation and 
keratinization, and to assess inflammation. Thirteen-cis-RA treatment 
resulted in a mild decrease of scaling and induration. Erythema however 
increased. No statistically significant difference in biological effects 
was achieved between 13-cis-RA and placebo treated lesions and no changes 
in expression of the immunohistochemical markers were seen. 

============================================================ 
76.) In vivo effects of 13-cis retinoic acid treatment on the concentration 
of proteins and lipids in serum. 
============================================================ 
AU: Fex-GA; Aronsson-A; Andersson-A; Larsson-K; Nilsson-Ehle-P 
AD: Department of Clinical Chemistry, Lund University Hospital, Sweden. 
SO: Eur-J-Clin-Chem-Clin-Biochem. 1996 Jan; 34(1): 3-7 
ISSN: 0939-4974 
PY: 1996 
LA: ENGLISH 
CP: GERMANY 
AB: A number of serum components, whose concentrations or gene expression 
have been shown to be modulated by all-trans retinoic acid in vitro, were 
monitored in patients before and during treatment with Roaccutane (13-cis 
retinoic acid, 40-60 mg/day) for severe acne. The 13-cis retinoic acid 
concentration in serum rose from 5.25 +/- 1.09 to 593 +/- 65 nmol/l (mean 
+/- SD) 24 h after the latest dose. The concentration of all-trans retinoic 
acid in serum under Roaccutane treatment was measured in model experiments 
and shown to be 10-20 nmol/l i.e., 2-4 times the basal levels (4.65 +/- 
0.85 nmol/l) when the 13-cis retinoic acid concentration was 370-980 
nmol/l. The concentrations of creatine kinase-MB, apolipoprotein B, total 
cholesterol and LDL cholesterol increased significantly while the other 
measured serum components, including lipoprotein lipase activity, were 
unaffected by Roaccutane treatment. 

============================================================ 
77.) Effect of systemic administration of isotretinoin on blood lipids and 
fatty acids in acne patients. 
============================================================ 
AU: Ostlere-LS; Harris-D; Morse-Fisher-N; Wright-S 
AD: Department of Dermatology, Royal Free Hospital, School of Medicine, 
London, England. 
SO: Int-J-Dermatol. 1996 Mar; 35(3): 216-8 
ISSN: 0011-9059 
PY: 1996 
LA: ENGLISH 
CP: UNITED-STATES 
AB: BACKGROUND. In many studies, an increase in total cholesterol and 
triglycerides with isotretinoin therapy have been shown and investigators 
have commented on potential cardiovascular risk. A low intake of linoleic 
acid, the main essential fatty acid in man, may act as an independent risk 
factor for coronary heart disease. In vitro etretin alters both the 
incorporation of extracellular fatty acids into cell membranes and the 
fatty acid composition of the cell membrane itself. It is, therefore, 
important to establish whether isotetinoin has any effect on the metabolism 
of polyunsaturated fatty acids. METHODS. The effect of treatment with 
isotretinoin for 4 months on the metabolism of polyunsaturated fatty acids 
in patients with acne was assessed. Quantitative total cholesterol and 
triglycerides as well as plasma phospholipid, triglycerides, and 
cholesteryl ester fatty acids were measured in 12 patients and red cell 
phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol 
fatty acids were measured in 13 patients before and after isotretinoin 
therapy. RESULTS. There was a significant increase in the concentrations of 
cholesterol (P < 0.02) and triglycerides (P < 0.04) during treatment. There 
was no significant difference is plasma phospholipids, triglycerides, and 
cholesterol esters, or in the red cell phosphatidylethanolamine, 
phosphatidylcholine, and phosphatidylinositol during isotretinoin therapy. 
CONCLUSIONS. This study failed to demonstrate any effect of isotretinon on 
the metabolism of polyunsaturated fatty acids. There was a significant 
increase in total cholesterol and triglyceride levels following 
isotretinoin therapy supporting the findings of many previous studies. 

============================================================ 
78.) Ocular side effects associated with 13-cis-retinoic acid therapy for 
acne vulgaris: clinical features, alterations of tearfilm and conjunctival 
flora. 
============================================================ 
AU: Egger-SF; Huber-Spitzy-V; Bohler-K; Raff-M; Scholda-C; Barisani-T; 
Vecsei-VP 
AD: University Eye Clinic, Department A, University of Vienna, Austria. 
SO: Acta-Ophthalmol-Scand. 1995 Aug; 73(4): 355-7 
ISSN: 1395-3907 
PY: 1995 
LA: ENGLISH 
CP: DENMARK 
AB: Isotretinoin (13-cis-retinoic acid) is commonly used for the treatment 
of acne vulgaris. We included 55 patients in this prospective study, and 
inspected them before, while and after therapy with isotretinoin regarding 
ocular side effects. Careful slit-lamp inspection, measurement of 
break-up-time and Schirmer-test and microbiological investigations of the 
conjunctival flora were performed. While staphylococcus aureus was cultured 
from the conjunctival sac before application of isotretinoin in 7.3%, this 
percentage increased to 61.8% during therapy. A pathological decrease of 
break-up-time was realized in 69.1% of the cases, the development of 
blepharitis in 40%. But in spite of the alteration of conjunctival flora, 
bacterial conjunctivitis developed in just 7.3% of the cases. However, only 
34.5% of the patients showed symptoms of a conjunctivitis sicca, in spite 
of the impressive diminution of break-up-time in so many cases. All ocular 
side effects of isotretinoin were treatable and disappeared completely 
within 1 month after stopping therapy. 

============================================================ 
79.) Retinoids and fibrinolysis. 
============================================================ 
AU: Back-O; Nilsson-TK 
AD: Department of Dermatology, University Hospital, Umea, Sweden. 
SO: Acta-Derm-Venereol. 1995 Jul; 75(4): 290-2 
ISSN: 0001-5555 
PY: 1995 
LA: ENGLISH 
CP: NORWAY 
AB: Vitamin A and its analogues have been reported to increase the release 
of tissue plasminogen activator in vitro. The aim of the present study was 
to reevaluate these findings and to investigate whether retinoids in doses 
used in dermatological therapy could enhance the release of endothelial 
fibrinolytic factors. Our results showed that endothelial cells incubated 
in vitro with retinoic acid increased the release of tissue plasminogen 
activator to the supernatant without concomitant secretion of plasminogen 
activator inhibitor-1. In patients treated with isotretinoin or etretinate 
these findings were confirmed, showing enhanced baseline tissue plasminogen 
activator concentrations in plasma in association with unchanged levels of 
plasminogen activator inhibitor-1 and von Willebrand factor. These findings 
are consistent with chronically augmented tissue plasminogen activator 
secretion without evidence of endothelial cell damage and may be of 
importance for the interpretation of the safety of lon-term therapy with 
regard to retinoid-induced hyperlipemia and the development of 
cardiovascular disease. 

============================================================ 
80.) Massive isotretinoin intoxication. 
============================================================ 
AU: Aubin-S; Lorette-G; Muller-C; Vaillant-L 
AD: Department of Dermatology, University Medical Center, Tours, France. 
SO: Clin-Exp-Dermatol. 1995 Jul; 20(4): 348-50 
ISSN: 0307-6938 
PY: 1995 
LA: ENGLISH 
CP: ENGLAND 
AB: We report a case of acute intoxication due to a massive overdose of 
isotretinoin. A 29-year-old male patient ingested 900 mg of isotretinoin 
corresponding to 12.5 mg (kg/day) or 30 times the prescribed dosage and 1 
day later the patient experienced mild headache. Forty-eight hours later, 
cheilitis, diffuse cutaneous xerosis and desquamation of the forehead and 
of the external auditory meatus occurred; cutaneous xerosis and cheilitis 
resolved spontaneously, We determined the serum level of isotretinoin and 
of 4-oxo-isotretinoin, its natural metabolite in sera taken 4, 5, 6 and 11 
days following ingestion. The side-effects were mild and represented only 
exacerbations of some common isotretinoin side-effects. To date, three 
other cases of isotretinoin overdosage have been reported. There was a low 
toxicity of isotretinoin overdose. 

============================================================ 
81.) [Isotretinoin (RoAccutane) embryopathy. A case report] 
============================================================ 
TO: Embryopathie liee a l'isotretinoine (RoAccutane). A propos d'une 
observation. 
AU: Pilorget-H; Alessandri-JL; Montbrun-A; Ah-Hot-M; Orvain-E; Tilmont-P 
AD: Service de Neonatologie et Reanimation Neonatale et Pediatrique, Centre 
Hospitalier, Saint-Denis, La Reunion. 
SO: J-Gynecol-Obstet-Biol-Reprod-Paris. 1995; 24(5): 511-5 
ISSN: 0368-2315 
PY: 1995 
LA: FRENCH; NON-ENGLISH 
CP: FRANCE 
AB: Retinoids are synthetic vitamin A derivatives, particularly used in 
dermatology. Their prescription in women of childbearing age can cause, if 
pregnancy occurs, a serious malformative embryopathy, mainly involving 
external ear, brain and heart. A neonatal case caused by isotretinoin 
(RoAccutane) emphasizes the clinical and epidemiological data concerning 
this embryopathy. The aetiopathological hypothesis of an interaction 
between isotretinoin and Hox genes is advanced. Prophylactic measures are 
difficult since neonatal reported cases are uncommon, but antenatal 
exposition to this strong teratogenic agent results in multiple spontaneous 
abortions or pregnancy interruptions. 

============================================================ 
82.) Similarities in genetic mental retardation and neuroteratogenic 
Syndromes. 
============================================================ 
Adams J 
Department of Psychology, University of Massachusetts/Boston 02125, USA. 
Pharmacol Biochem Behav (UNITED STATES) Dec 1996 55 (4) p683-90 
ISSN: 0091-3057 
Language: ENGLISH 
Document Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL 
Journal Announcement: 9706 
Subfile: INDEX MEDICUS 
Principles and mechanisms of neurobehavioral teratogenesis are used to 
show commonalities between manifestations of abnormal development 
consequent to genetic abnormality or teratogenic exposure. A comparison 
and contrast of both the neuropathological and neuropsychological 
characteristics of children with early embryonic exposure to isotretinoin 
(Accutane) or with selected mental retardation syndromes is presented. 
Putative mechanisms of retinoid teratogenesis through the disruption of 
normal retinoid-triggered embryogenesis and the alteration of homeobox 
gene expression are discussed. Interference with homeobox gene expression 
as an avenue to the perturbation of early developmental processes and the 
production of hindbrain and craniofacial abnormalities is then proposed as 
a common basis for the translation and expression of several genetic 
mental retardation syndromes. Finally, dose-response effects and other 
modulators of vulnerability to abnormal development are used to provide a 
conceptual framework for the understanding of variability in the 
expression of genetically caused abnormalities. (75 References) 

============================================================ 
83.) Development of human papillomavirus type 16 associated squamous cell 
carcinoma of the scrotum in a patient with Darier's disease treated with 
systemic isotretinoin. 
============================================================ 
J Urol 1995 Jun;153(6):1940-3 

Orihuela E, Tyring SK, Pow-Sang M, Dozier S, Cirelli R, Arany I, Rady P, 
Sanchez R 
Department of Surgery, University of Texas Medical Branch, Galveston, USA. 

In contrast to squamous cell carcinoma of the penis, scrotal carcinoma has 
historically been associated with exposure to environmental or industrial 
carcinogens and has only rarely been correlated with human papillomavirus. 
We report on a patient with squamous cell carcinoma of the scrotum in which 
human papillomavirus type 16 was integrated into the tumor cell genome, 
suggesting a causal role of human papillomavirus in the development of 
squamous cell carcinoma of the scrotum. Other unique features of our case 
include the presence of Darier's disease, an uncommon genodermatosis, and 
treatment with oral retinoids, which have prophylactic value in the 
prevention of cutaneous malignancies. 

============================================================ 
84.) Isotretinoin therapy is associated with early skeletal radiographic 
changes. 
============================================================ 
J Am Acad Dermatol 1984 Jun;10(6):1024-9 

Ellis CN, Madison KC, Pennes DR, Martel W, Voorhees JJ 
Eight patients with disorders of keratinization (six with ichthyosis, one 
with Darier's disease, and one with palmar-plantar keratoderma) were 
treated with isotretinoin for 9 months (1 patient) to 1 year (7 patients). 
The patients ranged from 5 to 26 years of age. The average isotretinoin 
dose was 2 mg/kg/day (range, 1.0-2.9 mg/kg/day). Radiographic skeletal 
surveys were performed prior to therapy, and after 6 months and 1 year of 
therapy. After 1 year of isotretinoin treatment, six of the eight patients 
had small but unequivocal skeletal hyperostoses. Five of the patients had 
multiple hyperostoses. While only two patients were judged to have 
hyperostoses after 6 months of isotretinoin therapy during prospective 
evaluation, retrospective comparison with the radiographs obtained after 1 
year revealed skeletal hyperostoses after 6 months of treatment in an 
additional three patients. Between 6 months and 1 year of therapy, some of 
the hyperostoses remained unchanged while others had progressed. In three 
patients, hyperostoses were seen at 12 months that were not detectable at 6 
months. Based on this prospective study of skeletal changes during 
isotretinoin therapy, we recommend that patients taking high doses of 
isotretinoin for long periods be monitored radiographically. 

============================================================ 
85.) Bone densities in patients receiving isotretinoin for cystic acne. 
============================================================ 
Arch Dermatol 1999 Aug;135(8):961-5 

Leachman SA, Insogna KL, Katz L, Ellison A, Milstone LM 
Department of Dermatology, Yale University School of Medicine, New Haven, 
CT 06520-8059, USA. 

BACKGROUND: Few studies have been done of bone densities in humans 
receiving retinoids, despite a substantial amount of literature concerning 
retinoid-induced osteoporosis in animals. We prospectively measured bone 
density and calcium metabolism in young men (aged 17-25 years) receiving 
oral isotretinoin for cystic acne and in a group of healthy volunteers 
(aged 19-26 years). OBSERVATIONS: Compared with that in healthy control 
subjects, mean bone density was lower at all sites (spine, femoral neck, 
and Ward triangle) and was considerably more variable at the spine in young 
men with cystic acne even before treatment. Bone density at the Ward 
triangle decreased a mean of 4.4% (P = .03) after 6 months of isotretinoin 
use (1 mg/kg of body weight). Four patients showed decreased density of 
more than 9% at the Ward triangle. The difference between the mean change 
in bone density in the patient group and in the control group was 
significant at the Ward triangle (P = .04) but not at the other sites. 
Measurements of calcium metabolism did not change over time in either 
group. CONCLUSIONS: A loss of bone density occurring in the absence of 
measurable alterations of calcium metabolism is likely to be a direct 
effect of retinoids on bone. Further study of retinoid-induced osteoporosis 
in humans and of bone density in patients with cystic acne is needed. 

============================================================ 
86.) Oral isotretinoin therapy in severe acne induces transient suppression 
of biochemical markers of bone turnover and calcium homeostasis. 
============================================================ 
Author 
Kindmark A; Rollman O; Mallmin H; Petr&acute;en-Mallmin M; Ljunghall S; Melhus H 
Address 
Department of Internal Medicine, University Hospital, Uppsala, Sweden. 
Source 
Acta Derm Venereol, 78(4):266-9 1998 Jul 
Abstract 
Although dietary vitamin A is required for normal growth and development, 
long-term or high-dose administration of vitamin A derivatives (retinoids) 
may produce a variety of skeletal side-effects in man. In this study we 
investigated the early effects of oral isotretinoin therapy on bone 
turnover and calcium homeostasis in eleven consecutive patients with 
nodulocystic acne. The effects on bone metabolism were correlated to 
radiological and bone mineral density measurements following drug therapy 
for six months. Markers of bone turnover, i.e. serum osteocalcin, the 
carboxyterminal propeptide of type I collagen, bone specific alkaline 
phosphatase, the carboxyterminal telopeptide of type I collagen, and urine 
levels of calcium and hydroxyproline decreased significantly within five 
days of treatment (p < 0.05). There was also a statistically significant 
decrease in serum calcium, with a minimum on day five, and a marked 
increase in serum parathyroid hormone (p < 0.05). With continued treatment, 
however, the abnormal levels of these markers returned to baseline values 
within 14 days. No significant roentgenological changes or effects on bone 
mineral density were found in response to the drug. The observed inhibitory 
effects of isotretinoin on bone turnover, despite elevated parathyroid 
hormone levels, indicates that the drug exerts a direct effect on bone 
tissue. 

============================================================ 
87.) Miliaria crystallina occurring in a patient treated with isotretinoin. 
============================================================ 
Cutis 1986 Oct;38(4):275-6 

Gupta AK, Ellis CN, Madison KC, Voorhees JJ 
A case of miliaria crystallina occurring with isotretinoin therapy in a 
patient with lamellar ichthyosis is described. To our knowledge, the 
association of miliaria crystallina with isotretinoin therapy has not been 
previously reported. 

============================================================ 
88.) Steady-state pharmacokinetics of isotretinoin and its 4-oxo 
metabolite: implications for fetal safety. 
============================================================ 
J Clin Pharmacol 1998 Oct;38(10):926-30 

Nulman I, Berkovitch M, Klein J, Pastuszak A, Lester RS, Shear N, Koren G 
Department of Pediatrics and Research Institute, The Hospital for Sick 
Children, Toronto, The University of Toronto, Ontario, Canada. 

Isotretinoin is the most potent human teratogen on the market. Women for 
whom contraception fails may conceive during or soon after discontinuing 
isotretinoin therapy, making its elimination kinetics a crucial determinant 
of fetal safety. The steady-state pharmacokinetics of isotretinoin and its 
major 4-oxo metabolite were studied in 16 adult patients treated for acne 
who were receiving doses that ranged from 0.47 to 1.7 mg/kg daily. This is 
the first study of the pharmacokinetics of isotretinoin in women of 
childbearing age (n = 11). The clinical efficacy and tolerability of 
isotretinoin was investigated, and the correlation between these data and 
steady-state serum concentrations of isotretinoin was tested. The 
concentration-time data best fitted a two-compartment open model with 
linear elimination. There was no correlation between efficacy and 
tolerability of isotretinoin and steady-state serum concentrations. There 
was no correlation between dose of isotretinoin and steady-state 
concentration, due to the large variability in apparent clearance. Values 
for elimination half-life (t1/2) of isotretinoin and its metabolite were 
29+/-40 hours and 22+/-10 hours, respectively. These data suggest a longer 
elimination t1/2 of the parent drug than previously reported. This is 
probably due to the longer sampling time used in this study (as long as 28 
days). This study suggests that a greater variability exists in the safe 
time after discontinuation of the drug for onset of conception. 

============================================================ 
89.) Isotretinoin intoxication in attempted suicide. 
============================================================ 
Acta Derm Venereol 1986;66(5):452-3 

Lindemayr H 
Only mild symptoms of retinoid intoxication--headache, hallucinations and 
vertebral pain--were observed after ingestion of 800 mg isotretinoin among 
other drugs. Transaminases and serum lipids were found within normal range 
five days later. Mucocutaneous effects due to overdosage were absent. 

============================================================ 
90.) Isotretinoin: possible cause of acute seizure and confusion. 
============================================================ 
Ann Pharmacother 1993 Jun;27(6):793-4 

Marroni M, Bellomo G, Bucaneve G, Stagni G, Baldelli F 
Publication Types: 
Letter 
============================================================ 
============================================================ 
91.) Median canaliform dystrophy following isotretinoin therapy [letter] 
============================================================ 
Author 
Dharmagunawardena B; Charles-Holmes R 
Source 
Br J Dermatol, 137(4):658-9 1997 Oct 
============================================================ 
============================================================ 
92.) Mood changes associated with isotretinoin and substance abuse [letter] 
============================================================ 
Author 
Kovacs SO; Mallory SB 
Source 
Pediatr Dermatol, 13(4):350 1996 Jul-Aug 
============================================================ 
============================================================ 
93.) Urethritis associated with isotretinoin therapy [letter] 
============================================================ 
Author 
Edwards S; Sonnex C 
Source 
Acta Derm Venereol, 77(4):330 1997 Jul 
============================================================ 
============================================================ 
94.) Renal impairment induced by isotretinoin [letter] 
============================================================ 
Author 
Pavese P; Kuentz F; Belleville C; Roug&acute;e PE; Elsener M 
Source 
Nephrol Dial Transplant, 12(6):1299 1997 Jun 
============================================================ 
============================================================ 
95.)Isotretinoin-induced pemphigus. 
============================================================ 
Acta Derm Venereol 1995 Sep;75(5):413 

Georgala S, Rigopoulos D, Gourgiotou K, Christofidou E 
Publication Types: 
Letter 
============================================================ 
============================================================ 
96.) Acute arthritis after isotretinoin. 
============================================================ 
Dermatology 1999;198(4):406-7 

Lehucher Ceyrac D 
Publication Types: 

Letter 
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DATA-MEDICOS/DERMAGIC-EXPRESS No 2-(80) 27/10/99 DR. JOSE LAPENTA R. 
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