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PubMed2004

Successful use of acitretin in conjunction with narrowband ultraviolet B phototherapy in a child with severe pustular psoriasis, von Zumbusch type.

Severe pustular psoriasis von Zumbusch type is a therapeutic challenge not only in adults, but even more in children. We report a 3(1/2)-year-old boy who developed a generalized flare of diffusely scattered pustules on erythematous skin which rapidly progressed to large exuding areas. The clinical presentation and investigations including histopathological examination of a biopsy and negative bacterial cultures were consistent with the diagnosis of pustular psoriasis von Zumbusch type. Upon initial treatment with methylprednisolone, acitretin and antibiotics the extent of the disease declined. However, several attempts to reduce the dose of the oral corticosteroid were followed by immediate severe flares. Additional treatment with narrowband ultraviolet B (NB-UVB, 311-313 nm UVB) resulted in a rapid arrest of disease activity and allowed the corticosteroid to be tapered off. After 10 irradiations the patient was both off steroid and disease free. NB-UVB therapy was subsequently reduced to twice-weekly exposures and acitretin gradually diminished to a maintenance dose of 0.3 mg kg(-1) daily. We conclude that NB-UVB in conjunction with acitretin is a potent therapeutic regimen for the treatment of severe pustular psoriasis von Zumbusch type in childhood.

Acitretin↗
PubMed2005

A review of acitretin, a systemic retinoid for the treatment of psoriasis.

Acitretin is a second-generation, systemic retinoid that has been approved for the treatment of psoriasis since 1997. It can be considered one of the treatments of choice for pustular and erythrodermic psoriasis. However, the efficacy of acitretin as a monotherapy for plaque psoriasis is less, although it is often used in combination therapy with other systemic psoriasis therapies, especially ultraviolet B or psoralen plus ultraviolet A phototherapy, to increase efficacy. Such combination treatments may potentially minimise toxicity by using lower doses of each of the two agents. All systemic retinoids are potent teratogens. The most common side effects are mucocutanous effects such as cheilitis and hair loss, which are dose-dependent. Acitretin is not immunosuppressive, is generally safe for long-term use and has no time limit restrictions, which makes it useful in combination therapy and for maintenance therapy.

Acitretin↗
PubMed2002

Nodulocystic acne and hidradenitis suppurativa treated with acitretin: a case report.

Nodulocystic acne is a dermatologic disease that can result in significant damage to the skin of the face, chest, and back. Hidradenitis suppurativa is a scarring disease of the skin that causes deep cysts and abscesses on the axillae and anogenital areas. We review a case of a patient with severe nodulocystic facial acne and hidradenitis suppurativa that was treated with 2 full courses of isotretinoin. Although the patient's condition improved, some draining cysts persisted on the face and groin. Because of the inability of isotretinoin to achieve long-term remission of the patient's condition, acitretin was considered as a possible maintenance drug. The patient was almost completely improved after 5 months' therapy with acitretin, which also was effectively used for ongoing maintenance. Acitretin may be a promising treatment for severe nodulocystic acne and hidradenitis suppurativa, which require long-term suppression when isotretinoin fails to give long-term remission.

Abscess↗
PubMed2001

Respiratory distress with acitretin, reversal by corticosteroid.

The retinoic acid derivatives are used for disorders of keratinization such as psoriasis. Acitretin, which is a synthetic, aromatic derivative of retinoic acid, is frequently used to treat psoriasis. The retinoic acid syndrome (RAS), described with all-trans-retinoic acid (ATRA) in patients with promyelocytic leukemia, is characterized by fever and respiratory distress. In this report we present a 32 year old male who developed high fever, dry cough and dyspnea while undergoing treatment with acitretin. During hospitalization, his acitretin was stopped and he was treated with corticosteroids. Significant improvement was observed within a few days.

Acitretin↗
PubMed1988

Serum lipid changes during acitretin (etretin) treatment of psoriasis and palmo-plantar pustulosis.

The effects of acitretin (free acid of etretinate) on the serum lipoprotein pattern and on the fat elimination in serum of 8 patients with psoriasis and 4 with palmo-plantar pustulosis were studied. The drug was given for 12 weeks; the average daily dose was 40 mg. Lipoprotein analyses and an intravenous fat tolerance test (IVFTT) were performed on three occasions (before, after 8 weeks' treatment, as well as 8 weeks after the end of the treatment). Acitretin increased the triglyceride concentration of the very low density lipoproteins by about 50% (p less than 0.02) and reduced the cholesterol of the high density lipoproteins significantly (p less than 0.001), leading to an increased low density/high density lipoprotein cholesterol ratio (p less than 0.02). The IVFTT indicated a lowering of the fat elimination capacity. All changes reverted to the original values after an 8-week wash-out period. The data suggest that the effects of acitretin on the lipoprotein metabolism resemble those of etretinate and isotretinoin.

Acitretin↗
PubMed1988

Intra-epidermal accumulation of polymorphonuclear leukocytes in persistent palmoplantar pustulosis during treatment with acitretin.

Six patients with persistent palmoplantar pustulosis were treated with acitretin, and the clinical response was compared with the effect on the intra-epidermal accumulation of polymorphonuclear PMN leukocytes. A prompt improvement of pustule formation and subsequently decreased scaling and erythema was seen in all patients. Following discontinuation of therapy, a relapse occurred within 2 weeks. With dosages of 45 or 55 mg/day, the clinical scores were only slightly better than with 25 or 35 mg/day. In patients using 25 mg acitretin a day, the leukotriene B4-induced intra-epidermal accumulation of polymorphonuclear leukocytes was not affected. However, a dosage of 35 mg/day resulted in a significant inhibition of PMN accumulation, dosages of 45 and 55 mg/day causing an even more pronounced inhibition of this process. Although the effect of different dosages of acitretin is not clearly expressed in the severity scores, the dose-dependent effect on PMN chemotaxis in vivo might be of relevance when combination therapies are considered, in order to achieve a complete clinical clearance.

Acitretin↗
PubMed1988

Acitretin in the symptomatic therapy for severe recessive x-linked ichthyosis.

Eight men with severe recessive x-linked ichthyosis were treated with acitretin, the main metabolite of etretinate, during four months. All of the patients showed marked clinical improvement of scaling during therapy. Hypervitaminosis A-type adverse reactions were observed in all patients. Although the overall tolerance was good, therapy was interrupted in one atopic patient because of pruritus. There were no undesirable laboratory changes in values. Thirty-five milligrams of acitretin daily provided the best efficacy, with minimal side effects. The beneficial effect of this retinoid lasted between four and six weeks after therapy was stopped. These results suggest that acitretin is a useful agent in the symptomatic therapy of severe recessive x-linked ichthyosis resistant to topical therapeutic modalities. Good results with this agent can be achieved with interval therapy adjusted to seasonal variations of the skin symptoms.

Acitretin↗
PubMed1988

Papillon-Lefèvre syndrome. Ultrastructural study and successful treatment with acitretin.

Four siblings affected by Papillon-Lefèvre syndrome (PLS) ranged in age from 2 to 11 years. The parents were unaffected and parental consanguinity was present. The 2-year-old girl showed the early manifestations of PLS; that is, slight gingival swelling and erythema occurring simultaneously with minimal scaling of palms and soles. The other siblings, aged 5, 8, and 11 years, showed severe periodontopathy with tooth loss and marked palmoplantar keratoderma with a centripetal extension of the keratoses to the limbs and trunk. These three older siblings were treated with acitretin (Ro 10-1670), the free acid of etretinate, with complete clearing of the skin and healing of gingival pockets. Treatment was given for 16 months; teeth that erupted during therapy were free of periodontopathy and remained firmly anchored to the alveolar bone. In two of the children ultrastructural examination of involved skin was performed before and during acitretin treatment. Before treatment a large number of lipidlike vacuoles were found in corneocytes and in granulocytes; tonofilaments were reduced in number, and keratohyaline granules frequently showed a rectangular or globular shape. During treatment with acitretin these abnormalities diminished markedly. Thus, etretin is effective in treating PLS and, if treatment is started at an early age, should allow patients with PLS to have normal adult dentition.

Acitretin↗
PubMed1988

Efficiency of acitretin in the treatment of cutaneous lupus erythematosus.

Acitretin (etretin [Ro-10-1670]) is the major metabolite of etretinate with a much shorter elimination half-life. The drug was used in the treatment of 20 patients who had cutaneous lupus erythematosus. All patients responded to treatment, but in five, the result was unsatisfactory. In 15 patients, an excellent (total clearing) or good response (marked reduction of all lesions) was seen. In seven of them, acitretin was superior to previous therapy with antimalarials and/or systemic corticosteroids. In particular, five of six patients with subacute cutaneous lupus erythematosus showed complete clearing of their lesions, usually within two to four weeks. Side effects were the same as with etretinate. It is concluded that acitretin is a highly effective and well-tolerated drug in the treatment of cutaneous lupus erythematosus.

Acitretin↗
PubMed1988

Residual plasma concentrations of acitretin (Ro 10-1670) and its metabolite (Ro 13-7652) after chronic administration.

In order to study the elimination of Ro 10-1670 (acitretin) and Ro 13-7652, its 13-cis-isomeric metabolite after chronic administration, determination of the residual plasma concentrations of these two compounds were assayed in 9 patients in a range of 22-30 days following cessation of a 2- to 7.5-month course with daily oral doses of 10-50 mg of acitretin. A highly sensitive HPLC method was used (2 ng/ml). Residual plasma concentrations of Ro 10-1670 were below the quantification limit in all cases. Residual plasma concentrations of Ro 13-7652 were below the quantification limit in 7 cases and respectively of 3 and 4 ng/ml in the other 2 cases. These data appear to confirm the absence of storage of acitretin even after an extended course of therapy.

Acitretin↗
PubMed1993

In vivo percutaneous absorption of [14C]acitretin in the hairless guinea pig and in the rhesus monkey.

The oral administration of retinoids such as etretinate and acitretin (Ro 10-1670, CAS 55079-83-9), provides a successful therapeutic approach in various cutaneous diseases characterized by disturbed keratinization, e.g. psoriasis. Nevertheless oral therapy is often associated with systemic adverse effects. This makes a topical form with no or reduced systemic side effects desirable. Direct application of a topical acitretin formulation to the skin might result in therapeutic skin concentrations while minimizing systemic exposure. In the hairless guinea pig and in the rhesus monkey the percutaneous absorption of [14C]acitretin from an isopropylmyristate formulation (160 micrograms acitretin/2.5 cm2/animal) were investigated in vivo. After a 24 h exposure drug concentration in the skin was higher in the hairless guinea pig (620 ng-eq/g wet tissue) than in the rhesus monkey (380 ng-eq/g wet tissue). A similar observation was made comparing the 24 h absorption data determined as amount of drug excreted. The results are compared with in vitro absorption data using skin from the same species.

Acitretin↗
PubMed1997

Multiple squamous cell carcinomas in a psoriatic patient following high-dose photochemotherapy and cyclosporin treatment: response to long-term acitretin maintenance.

Cumulative toxicity is a well known limitation of antipsoriatic treatments. In particular, the induction of multiple squamous cell carcinomas following long-term PUVA treatment is well established. In the present report, a psoriatic patient is described who was treated for more than 14 years with photochemotherapy (PUVA) and who received excessive amounts of topical corticosteroids. The patient developed, in total, 34 squamous cell carcinomas. In all, three squamous cell carcinomas developed during long-term PUVA treatment, and 21 carcinomas appeared during 16 months of treatment with cyclosporin. Subsequently, a marked inhibition of the occurrence of new tumours occurred during prolonged treatment with acitretin, and no new tumours have appeared during the last 4 years of continuous treatment with this retinoid at a dose of 60 mg/day. Modulation of the expression of PUVA-induced squamous cell carcinomas by cyclosporin and acitretin are discussed. The present report lends support to the hypothesis that cyclosporin causes an increased occurrence of PUVA-induced carcinomas, whereas acitretin (60 mg/day) is of value in preventing the occurrence of new squamous cell carcinomas in patients who were treated with long-term PUVA.

Acitretin↗
PubMed1992

Effect of acitretin on the response to an intravenous glucose tolerance test in healthy volunteers.

The effect of the synthetic retinoid acitretin (A) on the disposition of blood glucose and on the serum insulin response following the IV infusion of 139 mmol glucose over 10 min (IGTT) has been investigated in six healthy subjects. The IGTT was performed on Days 1, 10 and 24. On Days 3 to 10 A 50 mg/d was administered. Several parameters of glucose disposition and insulin response (K-values, AUC) were assessed. As a methodological variant, the profiles over time of blood glucose and serum insulin were evaluated by model calculations using the 'minimal model'. Acitretin did not influence any parameter of glucose disposition. The area under the insulin-time curve (baseline corrected) was significantly decreased from 1.20 mU.min.l-1 on Day 1 to 0.89 mU.min.l-1 on Day 10, and was 0.91 mU.min.l-1 on Day 24. The model-derived 'insulin sensitivity' increased from 13.10(-4) l.mU-1.min-1 on Day 1 to 20.10(-4) l.mU-1.min-1 on Day 10 and was 18.10(-4) l.mU-1.min-1 on Day 24. The results suggest that A increased sensitivity to endogenous insulin. It supports a recent report showing greater insulin sensitivity in patients treated with the synthetic retinoid etretinate.

Acitretin↗
PubMed1990

Severe hepatotoxic reaction with progression to cirrhosis after use of a novel retinoid (acitretin).

We report the case of a 50-year-old female who suffered from severe palmar and plantar pustulosis. During treatment with acitretin, a novel oral retinoid, which is the main derivative of etretinate, the patient developed a severe hepatotoxic reaction. Subsequent histological studies strongly suggested the development of liver cirrhosis. Reversible elevation of serum aminotransferase values during treatment with acitretin has been reported. However, the present observation indicates that severe hepatotoxic injury may also follow treatment with this agent.

Acitretin↗
PubMed1991

A 12-month treatment of severe psoriasis with acitretin: results of a Canadian open multicenter study.

Both etretinate and its principal metabolite, acitretin, are efficacious in the treatment of psoriasis. Because patients with severe psoriasis often require chronic therapy, this study was undertaken to determine the efficacy, tolerability, and safety of acitretin in patients on continuous treatment for 12 months. The initial daily dose of 50 mg was taken for 4 weeks. Thereafter the dose was increased or decreased by 10 mg at monthly intervals (10 to 70 mg) to produce the optimal response with minimal toxicity. Seventy percent of the patients who completed 12 months of treatment showed marked improvement. All patients experienced adverse reactions; dry lips, hair loss, skin peeling, pruritus, and nail disorders were the most frequent. Fourteen patients were withdrawn from the study because of one or more intolerable adverse reactions.

Acitretin↗
PubMed1991

Acitretin in the treatment of severe disorders of keratinization. Results of an open study.

The purpose of this open, noncomparative study with acitretin (Ro 10-1670) was to evaluate the clinical response of patients with various nonpsoriatic disorders of keratinization and to establish for these patients the optimal dosage for both efficacy and tolerance. Thirty-three patients (21 adults and 12 children or adolescents) with ichthyoses, palmoplantar hyperkeratosis, or Darier's disease were treated for a period of 4 months. Most patients showed marked improvement or remission. The results obtained in congenital ichthyosiform erythroderma, lamellar ichthyosis, and Papillon-Lefèvre syndrome were judged as better than those usually reported with etretinate. The side effects observed in our patients were similar to those reported with etretinate, with the exception of scaling of palms and soles, which had an incidence and severity greater than expected with etretinate. The optimal acitretin dosage providing the best efficacy with minimal undesirable effects varied from patient to patient. The mean daily dose (+/- SD) was 27 +/- 11 mg in adults and 0.7 +/- 0.2 mg/kg in children or adolescents.

Acitretin↗
PubMed2005

Acitretin-induced enthesitis in a patient with psoriatic arthritis.

A patient with psoriatic arthritis and cutaneous psoriasis took acitretin for 10 years to treat his skin lesions. Radiographs disclosed exuberant ossifications in several entheses. Their features were not typical for psoriatic arthritis but were consistent with acitretin-induced hyperostosis. Retinoids are known to induce hyperostosis, most notably when they are used in high dosages and over long periods. The concomitant presence of two conditions affecting the entheses may explain the exuberant nature of the ossifications in our patient.

Acitretin↗
PubMed1999

Acitretin in psoriasis: an overview of adverse effects.

Oral retinoids are among the drugs of choice for pustular and erythrodermic psoriasis. In addition, retinoids are effective in combination with other topical and systemic agents for the treatment of plaque-type psoriasis. Acitretin, the active retinoid metabolite, has replaced etretinate in retinoid therapy of psoriasis because of its more favorable pharmacokinetic profile, including a significantly shorter half-life. Retinoids, including acitretin, are potent teratogens, leading to strict requirements for pregnancy prevention during and after their use. Other retinoid side effects are generally preventable or manageable through proper patient selection, dose adjustments, and routine monitoring. Mucocutaneous side effects such as cheilitis and hair loss are the most common dose-dependent side effects, requiring dose reduction in some patients. Less common effects such as hepatotoxicity, serum lipid alterations, pancreatitis, and possible skeletal effects are also discussed.

Abnormalities, Drug-Induced↗