Therapeutic Efficacy of Etretinate on Cutaneous-type Adult T-cell Leukemia-Lymphoma.

Cutaneous-type adult T-cell leukemia-lymphoma is treated with antiviral or skin-directed therapy. Medications that are used to treat skin lesions of cutaneous T-cell lymphomas are also used for the cutaneous-type adult T-cell leukemia-lymphoma. Etretinate, a synthetic retinoid, has been used for treating cutaneous T-cell lymphomas; however, its clinical effectiveness for the treatment of cutaneous-type adult T-cell leukemia-lymphoma has not been fully studied. We conducted a retrospective assessment of the efficacy and safety of etretinate in 9 patients with cutaneous-type adult T-cell leukemia-lymphoma. Complete and partial responses to etretinate were observed in 1 and 7 patients, respectively. Among the responders, remission was maintained for more than 6 years in 2 patients. These results suggest that etretinate is a promising treatment option for cutaneous-type adult T-cell leukemia-lymphoma.

Acitretin prescribing patterns in women of childbearing potential.

BACKGROUND: Acitretin is indicated for severe psoriasis, but it is also a potent teratogen whose use should be avoided in women of childbearing potential. Topical medications, phototherapy, cyclosporine A, and new biologic agents provide safer alternatives for women of childbearing age with moderate to severe psoriasis. PURPOSE: To determine the demographics of acitretin prescribing patterns as an assessment of acitretin use in women of child-bearing potential. METHODS: We examined National Ambulatory Medical Care Survey (NAMCS) data from the years 1990-2009 to determine demographic data on patients who were prescribed etretinate or acitretin. We used age under 50 as a proxy for childbearing potential. RESULTS: From 1996-2009, there were an estimated 29 million office visits for psoriasis. Females accounted for 14.3 million of these visits, and 6.5 million (45.6%) of them were under the age of 50. The NAMCS contained only one record of a female patient under the age of 50 being prescribed acitretin from 1996-2009, the years during which acitretin had been available in the United States. This corresponds to an estimated 2.3% of all psoriasis patients prescribed acitretin during this time (20,000 out of 890,000). LIMITATIONS: The NAMCS estimates national trends based on a large nationwide database. While the use of acitretin in women under 50 is low, the precision of the estimate is limited by the small sample size provided by this database. CONCLUSIONS: There are now many alternative treatments besides acitretin for women of childbearing potential with moderate to severe psoriasis. Acitretin is used at most infrequently in this population. In females of reproductive potential, acitretin should be reserved for non-pregnant patients who are unresponsive to other therapies or whose clinical condition contraindicates the use of other treatments.

Systemic retinoids in the management of ichthyoses and related skin types.

The term retinoid includes both natural and synthetic derivatives of vitamin A. Retinoid-containing treatments have been used since ~1550BC by the early Egyptians. Treatment of ichthyosiform disorders with retinoids dates back at least to the 1930s. Early use of high-dose vitamin A demonstrated efficacy, but because vitamin A is stored in the liver, toxicity limited usefulness. Interest turned to synthetic retinoids in an effort to enhance efficacy and limit toxicity. Acetretin, isotretinoin and, in the past etretinate, have provided the most effective therapy for ichthyosiform conditions. They have been used for a variety of ages, including in newborns with severe ichthyosis and for decades in some patients. Careful surveillance and management of mucous membrane, laboratory, skeletal, and teratogenic side effects has made systemic retinoids the mainstay of therapy for ichthyosis and related skin types.

Long-term efficacy of psoriasis vulgaris treatments: analysis of treatment with topical corticosteroid and/or vitamin D3 analog, oral cyclosporin, etretinate and phototherapy over a 35-year period, 1975-2010.

Various therapies have been tried for psoriasis. In Japan, biologics began to be used for psoriasis treatment in January 2010. Their clinical efficacy is well known, but biologics cannot be used in all psoriasis patients for reasons such as side-effects and cost. It is necessary to evaluate the effect of long-term psoriasis treatment, but there have been no reports evaluating long-term treatment. Therefore, the outcomes of patients who had been treated at the Tokai University Hospital for more than 5 years, before biological agents were released, were examined. Three categories, classified by initial severity, changes in severity by method of treatment and background characteristics, were investigated. In conclusion, cases of long-term treatment with a combination of topical corticosteroid and topical vitamin D3 analog or oral cyclosporin were found to be effective therapies. Patients with a history of diabetes mellitus or cardiovascular disease of psoriasis were likely to be treatment resistant.

Case report: psoriatic erythroderma with bilateral osseous bridge across the acetabulum.

Abnormal reactions accompanied by bone formation in the osteoarticular region induced by long-term administration of etretinate have been reported. We treated a patient who received continuous treatment of psoriatic erythroderma with etretinate for 7 years, and who had an osseous bridge that extended across the acetabulum over the femur on both sides. The patient experienced a major gait disturbance and eventually was unable to walk. Functional gait was restored by resecting the ossified regions and radiotherapy. Histologic sections of the ossified lesions showed enchondral ossification in the ligament attachment site in the joint margin, with advancing ossification along the articular capsule; the pattern was similar to that in diffuse idiopathic skeletal hyperostosis. This is the first report of an osseous bridge associated with long-term administration of etretinate extending across the acetabulum over the femur on both sides.

Enfermedad de injerto contra huésped crónica tratada con fotoféresis: a propósito de un caso / A case of chronic graft vs host disease treated with photopheresis

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Oral retinoid therapy for disorders of keratinization: single-centre retrospective 25 years' experience on 23 patients.

BACKGROUND: Over the last three decades, the oral retinoids etretinate and acitretin have revolutionized the treatment of disorders of keratinization (DOK). Many patients with DOK require life-long treatment with oral retinoids. However, the longest follow-up data of patients with DOK on oral retinoid therapy is 10 years for adults and up to 11 years for children. OBJECTIVES: The aim of our study was to collect long-term retrospective data including disease response, side-effects and pregnancy outcome in a cohort of patients with DOK who were among the first in the world to commence oral retinoids 25 years ago. METHODS: Between 1979 and 1981, 30 patients with DOK were commenced on oral etretinate in our department. Case notes of these patients were reviewed retrospectively, and patients interviewed where possible to obtain the following information: diagnosis, age when treatment commenced, duration of treatment, reason for discontinuation of therapy, side-effects, abnormal investigation results and pregnancy outcomes. RESULTS: Case notes of 23 of the 30 patients were available for review; of these, two patients were deceased and 14 were interviewed. In the 23 patients, the mean age of commencing treatment was 33.5 years (range 4.2-61) and the mean duration of etretinate therapy was 5.2 years (range 1 month to 14 years). Reasons for discontinuing treatment were an overall improvement in the skin disease (six of 23), no benefit +/- side-effects (11 of 23) and noncompliance (one of 23). Two patients died of causes unrelated to their skin disease or treatment, 12 and 4 years after stopping etretinate. Five patients (one female, four males) subsequently changed to acitretin and are currently continuing therapy. The mean total duration of retinoid therapy (etretinate and acitretin) for the four males was 23.7 years (range 20.6-25.1). The female patient continued intermittent courses (due to planned pregnancies) of oral retinoids for a total of 10.1 years over the last 25 years. Abnormal investigation results included elevated serum triglycerides and cholesterol (two of 23), isolated high triglycerides (three of 23), isolated high cholesterol (three of 23), worsening of liver enzymes in a patient with alcohol dependence, and elevated serum alkaline phosphatase (ALP) in healthy adults (three of 23). In two children, the elevated pretreatment ALP levels increased further after commencing etretinate but returned to normal in adulthood while treatment continued. One patient developed diffuse idiopathic skeletal hyperostosis after 21 years of retinoid therapy. One female patient had two early spontaneous abortions 2.75 and 3.2 years after discontinuing etretinate; she subsequently had two normal children. Two other females had normal children 1, 3 and 5 years after stopping etretinate. Two male patients fathered a total of three healthy children while on etretinate. CONCLUSIONS: This study provides the longest available follow-up data of children and adults with DOK on oral retinoid therapy. Such information is essential for clinicians and their patients with DOK embarking on life-long treatment with retinoids.

Lack of significant skeletal changes after long-term, low-dose retinoid therapy: case report and review of the literature.

BACKGROUND: Long-term systemic retinoid therapy has been associated with skeletal side effects. There have been reports of diffuse idiopathic skeletal hyperostosis (DISH) syndrome, calcification of ligaments, and osteoporosis, as well as premature fusion of epiphyses and modeling abnormalities of long bones, occurring in patients on chronic high-dose isotretinoin, etretinate, and acitretin therapy. Low-dose acitretin has been used for many years as monotherapy or in combination with other systemic therapies for psoriasis. Evidence to date suggests that the frequency of symptomatic bony effects is quite low in these patients. OBJECTIVE: To present the radiologic findings of a patient on long-term, low-dose acitretin and etretinate and to review the literature on the radiologic evidence of skeletal side effects during retinoid therapy. METHODS: Case report and literature search. RESULTS: A patient on low-dose acitretin had no significant radiologic abnormalities associated with retinoid use after 9 years of treatment. A review of the literature revealed conflicting reports on the incidence of radiologic abnormalities in patients on retinoid treatment. CONCLUSION: The evidence to date does not substantiate a clear link between radiologic skeletal abnormalities and long-term, low-dose acitretin or etretinate therapy.

Thrombocytopenia possibly induced by etretinate in a psoriatic patient.

A patient with psoriasis vulgaris developed multiple purpura on the extremities and hemorrhage at the oral mucosa and gingiva with marked thrombocytopenia. This thrombocytopenia was possibly induced by a retinoid agent, etretinate, from the clinical course and data. The total amount of etretinate administered was 2,410 mg over 191 days (41.9 mg/kg body weight, average 15.3 mg/day). A platelet transfusion partially restored the platelet count and the purpura and gingival hemorrhage disappeared approximately 10 days after the cessation of etretinate. However, the platelet count remains at 60-80 x 103/mm3 after two and a half years without etretinate therapy. Although there are only a few case reports of etretinate-induced thrombocytopenia, we should pay more attention to the peripheral platelet count during etretinate therapy.

Seguimiento del tratamiento con retinoides en niños con trastornos importantes de la queratinización / Follow-up of children with severe disorders of keratinization under retinoid therapy

Fundamento: los retinoides sistémicos son los fármacos de elección en el tratamiento de los trastornos graves de la queratinización. Objetivo: revisar la eficacia y los efectos secundarios del tratamiento con retinoides a largo plazo en niños con trastornos de la queratinización. Métodos: revisión retrospectiva del seguimiento de doce niños (cinco hombres y siete mujeres) con trastornos de la queratinización y tratados con retinoides orales (etretinato y/o acitretín) durante períodos de tiempo variables entre 7 y 68 meses. Resultados: todos los pacientes excepto uno mostraron mejoría de su enfermedad. Los efectos secundarios comunes (queilitis y sequedad cutánea) fueron casi constantes. Se produjeron elevaciones de las transaminasas en cinco pacientes, que se controlaron al pasar el tiempo o reducir la dosis. No se produjeron efectos secundarios óseos directamente atribuibles a la medicación. Conclusiones: los retinoides orales son eficaces y seguros en el manejo a largo plazo de los trastornos de la queratinización en los niños (AU)

Etretinate augments interferon beta-1b effects on suppressor cells in multiple sclerosis.

BACKGROUND: Interferon beta treatment is only partially effective in multiple sclerosis (MS) suggesting a potential role for adjunctive therapies. Retinoids can augment the clinical efficacy of type 1 interferons in patients with cancer. We reasoned that the same might hold in MS. Interferon beta-1b added to peripheral blood mononuclear cells in vitro partially reverses the CD8 suppressor cell defect of patients with MS. All-trans retinoic acid added to peripheral blood mononuclear cells from untreated patients with MS or from controls potentiates this ability of interferon beta-1b to augment CD8 suppressor cell function in vitro. OBJECTIVE: To determine whether retinoid administration to patients with MS who are being treated with interferon beta-1b augments their CD8 suppressor cell function. SETTING: A university hospital MS clinic. PARTICIPANTS: Patients with MS who were being treated with interferon beta-1b, 14 patients with secondary progressive MS and 3 patients with relapsing remitting MS. RESULTS: Seventeen patients with MS received etretinate treatment for up to 6 months. Planned dosing was 10 mg 3 times daily for the first month, 25 mg twice daily for the second and third months, and 10 mg twice daily thereafter. The 25-mg twice daily dose was not well tolerated and of the 14 patients who remained in the phase 1 clinical trial through month 3 dose reduction to 10 mg thrice daily was required in 1 patient and to 10 mg twice daily in 4 patients. Eleven patients completed the trial. Etretinate treatment significantly augmented suppressor function over baseline values at 1, 3, and 6 months. No meaningful change was noted in disability or quality of life over the course of the phase 1 clinical trial. Neuropsychological testing of completers suggested improvement on selected aspects of verbal memory at 6 months compared with baseline values. CONCLUSIONS: Etretinate treatment at a dose of 10 mg twice or three times daily augments suppressor cell function in patients with MS receiving interferon beta-1b. Higher dose etretinate treatment (25 mg twice daily) is poorly tolerated by patients with MS. Even at 10 mg twice daily adverse experiences involving the mucous membranes and the skin become troublesome for some, but not all, patients. Whether pulse therapy or administration of retinoid restricted to the day of interferon beta dosing will also augment suppressor function, while being better tolerated, remains to be determined.

[A case of intestinal Behçet's disease with abnormal ossification complicated by myelodysplastic syndrome, symptoms revealed after the perforation of ileum ulcer].

A 39-year-old man, who had been treated with Etretinate for common wart since he was 29 years old, was admitted to Taga General Hospital complaining of gradually deteriorating lumbago and bilateral hip joints pain in September, 1996. His lower vertebrae and bilateral hip joints showed abnormal ossification on X-ray. The bone scintigraphy indicated the existence of sacroiliitis. His platelet counts were fluctuating between 8 x 10(4) and 9 x 10(4)/mm3. During the follow-up in our out-patient clinic, he was suddenly suffered from severe abdominal pain in August, 1997 and admitted to our hospital. An emergency operation revealed multiple ulcers of his ileum with several perforations. Histological findings of the specimen of the ileum showed simple ulcer. After the operation, he had oral and genital ulcers. He did not have any signs or symptoms of ocular involvement. He was diagnosed as intestinal Behçet's disease. Because he showed gradually pancytopenia for several months after the operation, bone marrow aspiration was performed and a diagnosis of refractory anemia, a type of myelodysplastic syndrome (MDS), with trisomy of chromosome 8 was made. Abnormal ossification of his vertebrae and hip joints were considered to be related to Behçet's disease because an coexistence with sacroiliitis. On the other hand, there is no denying the effects of orally Etretinate administration. Several cases have been reported the association of MDS with Behçet's disease. In this case, the existence of MDS or various symptoms in Behçet's disease became apparent after the perforation of ileum ulcer. This paper discusses possible etiology of the relation between Behçet's disease and MDS, or the characteristic clinical course in this case.

Ulcerated atrophic striae from etretinate.

Oral retinoids such as etretinate and acitretin are commonly associated with dose-dependent, mucocutaneous side effects such as dryness, peeling, and fragility. Although these effects can be extreme in some patients and even require discontinuation of treatment, thinning of skin to the point of atrophy and ulceration has never been reported in the English literature. We present the case of a patient with psoriasis in whom ulcerated atrophic striae developed during etretinate therapy. After discontinuation of etretinate, all cutaneous ulcers resolved. Subsequently, the patient had a favorable response to oral calcitriol (1,25-dihydroxy vitamin D3), a novel therapy for psoriasis.

Computerized reminders to monitor liver function to improve the use of etretinate.

OBJECTIVE: to determine whether computerized reminders during the process of prescribing can improve the use of drugs requiring prior laboratory testing according to the indications listed in the Drug Package Insert. MEASURES: Change in proportion of appropriate prescribing and frequency of severe hepatotoxicity between pre- and post-intervention. METHODS: etretinate, a medication indicated for psoriasis, was selected as a monitored drug because it was the most prescribed of all the identified drugs that require specific prior laboratory tests. Computerized reminders are designed to alert a physician who is about to prescribe etretinate either without the alanine aminotransferase (ALT) test or the aspartate aminotransferase (AST) test within 3 months or despite abnormality in ALT or AST. Data on alerts were gathered by using electronic mail whenever alerts occurred. RESULTS: prescriptions of etretinate with normal ALT or AST results within the previous three months increased suddenly from 25.9% (127/491) in the pre-intervention period to 66.2% (353/533) in the post-intervention period (P < 0.0001). Moreover, three patients who used etretinate had markedly abnormal tests in the pre-intervention period, but none of the patients were classified in this way in the post-intervention period. CONCLUSIONS: the computerized reminders appear to improve physicians' use of a drug requiring specific prior laboratory tests.