EDITORIAL ESPANOL:

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ola amigos de la red, DERMAGIC en esta ocasión hace una revisión de la ISOTRETINOINA, LO BUENO, LO MALO Y LO FEO. Esta popular droga ha traído numerosos beneficios a la humanidad desde que fue introducida al mercado. Primeramente utilizada en el ACNÉ, posteriormente su uso se fue extendiendo hacia otras patologías DERMATOLÓGICAS Y NO DERMATOLÓGICAS siendo altamente efectiva. Pero también 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 también se ha demostrado que HA FALLADO en donde se consideraba su mayor EFECTO, en el acné. DE modo mis queridos amigos 

DERMÁGICOS cuando la vayan a utilizar pongan en el péndulo: LO BUENO, LO MALO Y LO FEO de esta medicina. 

Espero disfruten estas 96 apocalípticas !! referencias... 

Saludos,,,

Dr. José Lapenta R.,,,

 EDITORIAL ENGLISH:

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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,,,

Dr. José Lapenta R. 

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REFERENCIAS BIBLIOGRÁFICAS / BIBLIOGRAPHICAL REFERENCES 

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LO BUENO / THE GOOD 

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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. 

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LO MALO/ THE BAD 

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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. 

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LO FEO / THE UGLY 

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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. 

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LO BUENO / THE GOOD 

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1.) Oral retinoids in the treatment of seborrhoea and acne. 

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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. 

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2.) Treatment of acne with intermittent isotretinoin. 

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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. 

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3.) Isotretinoin for acne vulgaris. 

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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. 

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4.) [Therapy of severe acne and acne rosacea with oral 13-cis-retinoic acid]. 

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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. 

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5.) Roaccutane treatment guidelines: results of an international survey. 

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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 

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6.) The treatment of acne fulminans: a review of 25 cases. 

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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. 

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7.) Long-term results of isotretinoin in the treatment of 68 patients with 

hidradenitis suppurativa. 

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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. 

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8.) Multiple keratoacanthomas, giant keratoacanthoma and keratoacanthoma 

centrifugum marginatum: development in a single patient and treatment with 

oral isotretinoin. 

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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. 

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9.) Grover's disease treated with isotretinoin. Report of four cases. 

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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. 

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10.) Transient acantholytic dermatosis treated with isotretinoin. 

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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. 

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11.) A case of bullous transient acantholytic dermatosis. 

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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. 

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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. 

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13.) Isotretinoin and recombinant interferon alfa-2a therapy of metastatic 

malignant melanoma. 

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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. yarasade@dm.net.lb 

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) 

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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. 

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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. 

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84.) Isotretinoin therapy is associated with early skeletal radiographic 

changes. 

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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. 

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85.) Bone densities in patients receiving isotretinoin for cystic acne. 

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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. 

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86.) Oral isotretinoin therapy in severe acne induces transient suppression 

of biochemical markers of bone turnover and calcium homeostasis. 

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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. 

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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. 

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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. 

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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. 

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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 

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91.) Median canaliform dystrophy following isotretinoin therapy [letter] 

============================================================ 

Author 

Dharmagunawardena B; Charles-Holmes R 

Source 

Br J Dermatol, 137(4):658-9 1997 Oct 

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92.) Mood changes associated with isotretinoin and substance abuse [letter] 

============================================================ 

Author 

Kovacs SO; Mallory SB 

Source 

Pediatr Dermatol, 13(4):350 1996 Jul-Aug 

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93.) Urethritis associated with isotretinoin therapy [letter] 

============================================================ 

Author 

Edwards S; Sonnex C 

Source 

Acta Derm Venereol, 77(4):330 1997 Jul 

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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 

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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 

=================================================================== 

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

Produced by Dr. José Lapenta R. Dermatologist
Venezuela 1.998-2.024

Producido por Dr. José Lapenta R. Dermatólogo Venezuela 1.998-2.0024

Tlf: 0414-2976087 - 04127766810