Alitretinoin as a Treatment Modality for Ichthyosis in Women of Childbearing Age: A Case Series and Review of the Literature.

BACKGROUND: Acitretin, a synthetic vitamin A derivative, is the most studied and widely used oral retinoid for ichthyoses. Its major disadvantage is the need for contraceptive measures during 3 years after discontinuation. An alternative is needed for women of childbearing age. With alitretinoin, another retinoid, pregnancy is considered safe 1 month after discontinuation. OBJECTIVES: The aim of this study was to provide evidence for alitretinoin as an alternative for acitretin for ichthyosis in women of childbearing age. Our experience is shared in a case series combined with an overview of the current literature. METHODS: Nine women of childbearing age (19-31 years, median 21) with different subtypes of ichthyosis (autosomal recessive congenital ichthyosis, (superficial) epidermolytic ichthyosis, erythrokeratoderma variabilis, and epidermolytic epidermal nevi, a mosaic form of epidermolytic ichthyosis) were included and treated with 30 mg alitretinoin during 2-28 months. Severity was measured by Ichthyosis Area Severity Index (IASI) and Investigator Global Assessment (IGA). A literature search in Pubmed using the Mesh terms "alitretinoin," "skin diseases, genetic" and "ichthyosis" was performed. RESULTS: Significant reduction in the mean scores of IGA, IASI-erythema, IASI-scaling, and IASI-total was seen. Seven patients are still being treated, 1 patient stopped to become pregnant, 1 patient discontinued due to financial reasons. Observed side effects were reversible headache (n = 6), asteatotic eczema (n = 1), "not feeling well" temporarily (n = 1), and easier blistering of the feet (n = 1). The literature search resulted in six case reports and case series about alitretinoin in ichthyosis and ichthyosis syndromes with in total 29 patients. The vast majority of articles (21/29) reported significant improvement or even complete remission of skin symptoms. However, validated outcome measures to support these results were lacking. Side effects (n = 16) were relatively mild, except for benign intracranial hypertension (n = 1) and autoimmune hypothyroidism (n = 1). CONCLUSION: Our study shows, with validated outcome measures, that alitretinoin is effective to mitigate the symptoms of ichthyosis in women of childbearing age and a suitable alternative to acitretin.

Scabies in a 14-year-old girl with superficial epidermolytic ichthyosis.

A 14-year-old girl who reported generalized scaling and hyperkeratosis since age 1 year presented with severe pruritus of several months' duration. Scabies mites were detected, and molecular genetic analysis subsequently revealed a rare pathogenic variant in the keratin 2 (KRT2) gene, confirming a diagnosis of superficial epidermolytic ichthyosis. Treatment with oral ivermectin led to complete remission of symptoms. Disorders of keratinization can mimic clinical signs of scabies, leading to a delay in diagnosis.

Bilateral Systematised Epidermolytic Epidermal Nevus: A case report.

Verrucous epidermal nevi (VEN) are benign congenital hamartomas consisting of keratinocytes. Histological examination mostly exhibits hyperkeratosis, acanthosis, papillomatosis and, rarely, the features of epidermolytic hyperkeratosis (EHK). We report a case of a 6-year-old boy who presented at Aga Khan University Hospital, Karachi, Pakistan with bilaterally symmetrical linear epidermal nevi following Blaschko's lines and showing epidermolytic hyperkeratosis on histology. The patient was treated with topical keratolytics and emolients which led to considerable improvement. To the best of the authors' knowledge, this is the first report of VEN from Pakistan.

Long-term safety and efficacy of continuous acitretin monotherapy for three children with different severe hyperkeratotic disorders in China.

Long-term systemic treatment with acitretin for severe hyperkeratotic disorders is needed to maintain quality of life of afflicted patients, but treatment has been limited owing to its potential side-effects including skeletal malformations, particularly for children during their growth and development. A retrospective investigation was conducted with three children afflicted with a severe hyperkeratotic disorder, namely Darier's disease, bullous ichthyosiform erythroderma or lamellar ichthyosis, who were continuously maintained on 0.2-0.3 mg/kg per day acitretin for more than 12 years after an initial period at a larger acitretin dose to bring each disease under control. The patients had good responses to acitretin treatment, which was assessed for safety, skeletal abnormalities, growth retardation and other potential side-effects. Acitretin monotherapy was an effective treatment for these children, and maintenance doses were well tolerated with no skeletal or other observable side-effects during the course of the study.

[Topical treatment of infections, tumors and hyperkeratotic disorders]. / Topische Therapie von Infektionen, Hauttumoren und Hyperkeratosen.

In this review substances for the topical treatment of skin infections, skin tumors and hyperkeratotic disorders are presented. Substances with specific actions as topical antimycotic, antibiotic, antiseptic, antiviral and antiparasitic agents as well as diclofenac in hyaluronic acid, 5-fluoruracil, imiquimod, ingenol mebutate, bexarotene, mechlorethamine, BCNU, alitretinoin, silicone gel, salicylic acid and urea are discussed with respect to their mode of action, indication and side effects.

Systematized epidermal nevus with epidermolytic hyperkeratosis improving with topical calcipotriol/betametasone dipropionate combination ointment.

We present the case of a 5-year-old boy who presented with systematized epidermal nevus with evidence of epidermolytic hyperkeratosis on skin biopsy. He was otherwise well, with normal growth and development and no evidence of other organ system involvement. He had experienced only mild improvement with potent topical corticosteroids. He reported more-marked improvement after 2 months of topical calcipotriol/betamethasone dipropionate combination ointment once a day to the lesions. Extensive epidermal nevi can lead to severe cosmetic disfigurement. We recommend a trial of topical calcipotriol/betamethasone dipropionate ointment for patients with extensive epidermal nevus not amenable to surgical treatment.

Generalized and naevoid epidermolytic ichthyosis in Denmark: clinical and mutational findings.

A Danish-Swedish collaboration was established to identify and classify a Danish cohort of patients with epidermolytic ichthyosis, also known as epidermolytic hyperkeratosis. Patients were recruited from 5 dermatology departments in Denmark, and data were obtained using a structured questionnaire and a systematic examination together with photographs, histopathological descriptions and blood samples for mutational analysis. Sixteen patients from 12 families with generalized or naevoid epidermolytic ichthyosis and ichthyosis bullosa of Siemens were identified. Five families had mutations in K1 and 6 families had mutations in K10. Nine patients had been treated with systemic retinoids (etretinate, acitretin, isotretinoin or alitretinoin), but only 3 patients had acceptable treatment responses and chose to continue therapy. In conclusion epidermolytic ichthyosis is a rare disease with a prevalence of approximately 1 in 350,000 in Denmark and a high percentage of de novo mutations (75%). We identified 4 novel disease-causing mutations.

[Assessment of psoriatic nail lesions therapy by means of nail psoriasis severity index].

The problem of psoriatic nail lesions is known for a long time. According to various authors, psoriatic onychodystrophy has been diagnosed in 15-78% of patients with psoriasis. At the same time, we know that the treatment of psoriatic nail lesions is not always successful. The aim of the study was to evaluate the therapeutic efficacy of the drug onypso in the complex treatment of patients with psoriasis by means of NAPSI index. We observed 39 patients with psoriasis (20 men and 19 women at the age of 19 to 65 years with disease duration of 1 year to 25 years). The distribution of clinical manifestations of psoriatic onychodystrophy was as follow: thimble symptom -150 plates, subungual hyperkeratosis lesion type - 90 plates, onycholysis lesion type was observed in 50 plates. As a systemic treatment we used the cytostatic agent methotrexate - parenteral administration of 25 mg (once a week). In duration of total treatment course the patient received 90 -120 mg. Local treatment was provided by means of varnish onypso (once a day for 6 months). The survey revealed that at 7 weeks of treatment there was a 25 % reduction of initial value of NAPSI index, at the end of 14 weeks of therapy the above mentioned index was reduced for 50 % and at the 24 weeks for 75% respectively. It should be noted, that resolution of the cutaneous pathology was much faster than improvement of the structure of affected nail plates. Thus, drug onypso proposed for the specific treatment of nail lesions used in the complex therapy of patients with psoriasis is simple in use, accessible, compliant and highly effective. As a conclusion, we can say that NAPSI method, used to determine the extent of lesions and the effectiveness of the therapy, can objectively evaluate the dynamics of clinical pathology of the nails and adequacy of used treatment.