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We describe a 60-year-old patient with verrucous carcinoma of the vulva, which recurred 6 years after simple vulvectomy and radiotherapy. Treatment with acitretin led to significant improvement and ongoing disease control has been achieved with low-dose maintenance therapy of 10 mg acitretin daily.
Retinoids and interferon (IFN)-alpha induce differentiation, affect cell proliferation and alter various immune parameters. In combination, their effects may be additive or even synergistic in the treatment of malignancy. We present a 53-year-old woman with stage IV CD30+ anaplastic large cell lymphoma with brain, lung and skin involvement. The patient had been on methotrexate for rheumatoid arthritis. After a combination of oral acitretin 50 mg daily and IFN-alpha 3 million units subcutaneously 3 times per week, the skin lesions cleared within 2 months, lung lesions by 5 months and brain lesions by 7 months. Although we cannot exclude that methotrexate played a role in the development of this lymphoma and that its withdrawal contributed to the clearance of lesions, we propose that the patient's disease responded to the combination of acitretin and IFN-alpha.
BACKGROUND: Follicular mucinosis (FM) is a rare dermatosis characterized by mucin deposits in the pilosebaceous units. It is divided into a primary-benign type and a secondary type associated mostly with lymphomas. No standard effective therapy is available for the primary FM while in the secondary form treatment is aimed against the underlying disease. METHODS: We report a case of secondary FM in which a cutaneous T-cell lymphoma was detected 6 years after the initial eruption. RESULTS: Complete remission was achieved with combination therapy of interferon alpha-2b at a dose of 6 million U subcutaneously three times a week, and acitretin 35 mg/day, for 6 months. CONCLUSION: Regular clinical and histopathological evaluation is suggested for all patients with FM. For cases associated with cutaneous T-cell lymphoma the combination of interferon alpha and acitretin seems to be a good therapeutical approach.
Retinoids have been used for the treatment and suppression of cutaneous malignancies in patients with basal cell nevus syndrome, xeroderma pigmentosum, and in patients with recurrent skin cancers as a result of immunosuppression for renal transplantation. We report a 40-year-old male who began to develop multiple squamous cell carcinomas of the skin after treatment with PUVA for severe psoriasis. The numbers of squamous cell carcinomas increased when acitretin was discontinued and decreased when he was taking the drug at a dose of 25 mg daily. Acitretin should be considered as a maintenance therapy for psoriasis patients developing squamous cell carcinomas as a result of PUVA therapy.
KID syndrome is rare. We report a 17-year-old girl who presented with universally ichthyotic red hue on the face, trunk, and extremities along with deafness and keratitis since childhood. She was diagnosed with KID syndrome. Treatment with acitretin cleared the hyperkeratotic ichthyotic lesions with little effect on the cornea or hearing. Acitretin seems to be a promising new treatment in KID syndrome.
Generalized edema has been reported to be a rare side effect of systemic retinoids. We report a patient who developed localized bipedal edema from acitretin. Other causes of bipedal edema were excluded and withdrawal of acitretin led to resolution of the edema.
The dose response relationship to acitretin in five patients with Darier's disease was investigated. The patients received in the first 3 months 35 mg daily, and the dose was adjusted according to the clinical response. Four of the five patients showed a marked improvement with up to total clearance, although in two patients isomorphic reactions due to a relative overdose were seen. These isomorphic reactions improved with a reduction of dose. We suggest that treatment with acitretin is initiated at 10-25 mg daily with gradual adjustment of the dose.
We report four patients with severe erythrodermic, pustular psoriasis, or plaque-type psoriasis, who were treated with a combination of acitretin and bath PUVA. After 4 weeks out-patient treatment, the psoriasis in all patients had improved by > or = 90%. No patient had relapsed when reviewed at 3 months. No significant side-effects were seen with the combined retinoid/bath PUVA treatment. Acitretin and bath PUVA may be safely combined for the treatment of severe psoriasis.
Lichen amyloidosis (LA) is a chronic, pruritic skin disorder characterized by brownish-grey papules on extensor surfaces of legs and rarely on the trunk. Thioflavin T-positive amyloid deposits are found in the papillary dermis of affected skin, which is the only organ involved. A variety of therapeutic regimens for lichen amyloidosis have been described; however, in many cases with only limited effect. We report on two patients with lichen amyloidosis with typical clinical symptoms not responding to local treatment. A combined regimen with bath psoralen ultraviolet A (PUVA) and oral acitretin was initiated, resulting in nearly complete resolution of the papules and impressive relief from the severe pruritus. The beneficial response has persisted for 8 months. The suggested combined therapy with bath PUVA photochemotherapy and oral acitretin represents an efficacious and practical treatment modality for lichen amyloidosis with long-lasting effects.
Ten subjects were treated orally with acitretin (Ro 10-1670) over a period of 3 months. Before, during and after treatment, semen and blood analyses were performed to investigate drug-induced impairment of spermatogenesis and the hypothalamic-pituitary-gonadal axis. Our study concludes that acitretin in therapeutically effective doses does not influence spermatogenesis, sperm morphology, sperm motility and the hypothalamic-pituitary-gonadal axis.
The purpose of this prospective study was to investigate the ocular side effects of short-term therapy with oral acitretin (1 mg/kg/day) in 24 patients with severe and recalcitrant dermatoses. Apart from the routine ophthalmological examination, the following tests were performed: break-up time of tear film for the determination of its stability, Schirmer test for the assessment of lacrimal gland function, rose bengal staining for the detection of possible ocular surface damage and contrast sensitivity test for the evaluation of visual function. No statistically significant differences could be found between the pretreatment values of the assessed parameters and those obtained after 1 and 2 months of therapy. It seems reasonable, therefore, to suggest that ocular surface integrity and tear film and visual function are not affected by short-term oral acitretin administration.
A 57-year-old female patient with widespread chronic plaque psoriasis and a 32-year-old male patient with severe oral lichen planus are reported, who developed sensory symptoms in the extremities 3 and 4 months after the onset of oral acitretin therapy, respectively. Both patients showed clinical and electrophysiological evidence of a sensory peripheral neuropathy, which completely resolved 2 and 2.5 years after discontinuation of oral acitretin administration, respectively.
The effects of acitretin and etretinate on angiogenesis induced in Balb/c mice by intradermal injection of keratinocyte tumor cell lines were evaluated. It was shown that both retinoids are capable of inhibiting angiogenesis evoked by a human epidermoid carcinoma cell line (A431). Acitretin, but not etretinate, inhibited also angiogenesis induced by the spontaneously transformed murine keratinocyte cell line Pam 212 and by the established tumorigenic SKv cell line harboring the HPV16 genome. We suggest that inhibition of blood vessel formation may be one of the mechanisms responsible for the anticancerogenic effect of retinoids.
Doses of 3 and 10 mg/kg/day acitretin were orally administered to female Wistar rats over a period of 6 weeks. Phospholipid classes, P-450 content, aminopyrine-N-demethylase (ADM) and 7-ethoxyresorufin-O-deethylase (7-ERO-D) activities were determined in the liver microsomes of the treated animals. Both dosages caused statistically significant alterations in rat liver microsomal phospholipid composition which may be associated with changes in the metabolic activity, ionic transport, cell-cell interaction and other processes of the hepatic cellular components. Furthermore, statistically significant alterations of P-450 isozyme activities were induced by both dosages. Our data suggest a possible interaction of acitretin with other drugs and endogenous substances metabolized by these enzyme systems.
Etretinate (Tigason, Tegison) and its active metabolite acitretin (Neotigason, Soriatane) are known teratogens. Pregnancy should be avoided during treatment and until 2 years after treatment discontinuation. The question is discussed whether a dose or a blood concentration of the drug below which there is no teratogenic risk can be determined. Animal experimental and human pharmacokinetic data are reviewed. An evaluation of the outcomes of pregnancies which occurred in mothers exposed to etretinate or acitretin was performed. A threshold dose in human therapy below which there is no risk of congenital malformation cannot be determined based on animal experimental data. With regard to pharmacokinetics, there are currently no data suggesting that blood levels of the drug below the detection limit of 2 ng/ml are associated with a teratogenic risk. The most useful information is given by reports in women who were exposed to either retinoid before or during pregnancy. The data indicate that the risk of spontaneous abortion or congenital malformation is high when the drug is administered during the first trimester of pregnancy. After treatment discontinuation, the risk is low since the number of abnormalities seems not to exceed those observed in a general population. There are currently no available data which suggest that the pregnancy warnings are inappropriate in terms of duration of contraception.
We prospectively analyzed skeletal changes of 16 patients who were treated with acitretin for various disorders of keratinization at doses of 10-50 mg/day (overall mean 0.4 mg/kg/day) for 7-12 months (mean 11.4 months). Skeletal changes from pretherapy findings were observed in 5 patients. In 4 of 5 patients they appeared to be linked to a preexisting degenerative pathology and could not be attributed to acitretin therapy. However, in 1 patient a spinal osseous side effect could not be excluded. No retinoid-induced extraspinal tendon or ligament calcifications were observed.
A randomized double-blind study was designed with 65 patients in order to clarify two points: (1) does addition of a retinoid to psoralen-ultra violet A photochemotherapy (PUVA) of severe psoriasis decrease the UVA energy required to achieve remission, and (2) is there a difference between two retinoids, i.e. etretinate and acitretin. Acitretin-PUVA treatment was significantly superior to placebo-PUVA with respect to several items (decrease in lesional scores after 6 weeks of therapy, number of PUVA exposures, and total dose of UVA until remission). There were also differences between the etretinate-PUVA and placebo-PUVA groups, but only the decrease in lesional scores reached statistical significance.
Monilethrix is a rare hereditary disorder that affects the hair and is characterized by shaft anomaly. There is no known treatment that successfully cures the condition. In this report we present a case of monilethrix in a 7-year-old girl treated with oral acitretin. A very good clinical and cosmetic result was obtained while treatment was continued. However, clinical symptoms recurred after discontinuation of acitretin therapy.