isotretinoin and Ichthyosis--Lamellar

In two severe congenital ichthyosis subtypes, autosomal recessive lamellar ichthyosis (ARCI-LI) and X-linked recessive ichthyosis (XLRI), cutaneous manifestations include widespread scaling. Approved topical treatment options are limited to emollients and keratolytics.. This analysis from the randomized phase IIb CONTROL study assessed whether the efficacy and safety of TMB-001, a novel topical isotretinoin ointment formulation, differed between ARCI-LI and XLRI subtypes.. Participants ≥ 9 years with genetically confirmed XLRI or ARCI-LI and ≥ 2 (of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with ≥ 3 scaling score were randomized 1 : 1 : 1 to TMB-001 0.05%/TMB-001 0.1%/vehicle, twice daily for 12 weeks. The proportion of participants with ≥ 50% reduction vs. baseline in VIIS scaling (VIIS 50; primary endpoint) and ≥ 2-grade reduction in Investigator's Global Assessment (IGA)-scaling score vs. baseline (key secondary endpoint) were evaluated. Adverse events (AEs) were monitored.. Among enrolled participants (TMB-001 0.05%, n = 11; 0.1%, n = 10; and vehicle, n = 12), 52% had ARCI-LI and 48% XLRI subtypes. Mean age was 33.6 and 35.4 years for participants with ARCI-LI and XLRI, respectively. Overall, 33%, 50% and 17% of participants with ARCI-LI and 100%, 33% and 75% of participants with XLRI achieved VIIS 50 in the TMB-001 0.05%, TMB-001 0.1% and vehicle groups, respectively (nominal P = 0.24 for 0.05% vs. vehicle, intent-to-treat population). Improvement of ≥ 2-grade IGA score was observed in 33%, 50% and 0% of participants with ARCI-LI and 83%, 33% and 25% of participants with XLRI in the TMB-001 0.05%, TMB-001 0.1% and vehicle groups, respectively (nominal P = 0.03 for 0.05% vs. vehicle, intention-to-treat population). Most AEs were application-site reactions.. Regardless of congenital ichthyosis subtype, TMB-001 demonstrated greater proportions of participants achieving VIIS 50 and ≥ 2-grade IGA improvement vs. vehicle.

Topics: Adult; Humans; Ichthyosiform Erythroderma, Congenital; Ichthyosis; Ichthyosis, Lamellar; Ichthyosis, X-Linked; Immunoglobulin A; Isotretinoin

Emollients and keratolytics are frequently used to manage symptoms of congenital ichthyosis (CI). Systemic retinoid treatment is complicated by teratogenicity and dose-limiting adverse effects.. This analysis from the randomized Phase IIb CONTROL study investigated the characteristics of participants who responded to treatment with TMB-001, a novel topical isotretinoin ointment formulation.. Participants ≥ 9 years of age with genetically confirmed CI and ≥ 2 (out of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with ≥ 3 scaling score were randomized 1 : 1 : 1 to TMB-001 0.05%, TMB-001 0.1% or vehicle, twice daily for 12 weeks. Efficacy endpoints included the proportion of participants with ≥ 50% reduction in VIIS-scaling (VIIS-50) compared with baseline and ≥ 2-grade reduction in Investigator's Global Assessment (IGA)-scaling score compared with baseline. Changes in body surface area (BSA) involvement, Dermatology Life Quality Index (DLQI) scores and Itch-Numeric Rating Scale (I-NRS) scores were assessed.. Among the 33 participants (11 randomized to TMB-001 0.05%, 10 to TMB-001 0.1% and 12 to vehicle), median age was 29 years (range 9-80), and most were male (64%) and White (79%). Baseline demographics were generally similar among participants who did or did not achieve TMB-001 treatment success. Participants who had lower mean BSA involvement and higher DLQI and I-NRS scores at baseline were more likely to achieve VIIS-50. Similarly, higher baseline DLQI and I-NRS scores were associated with IGA response; BSA involvement was similar for IGA responders vs. nonresponders.. Higher DLQI and I-NRS scores at baseline were associated with participants achieving treatment success by VIIS-50 and IGA response. Lower BSA involvement was associated with VIIS-50 success.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Double-Blind Method; Emollients; Female; Humans; Ichthyosis, Lamellar; Immunoglobulin A; Infant, Newborn; Isotretinoin; Male; Middle Aged; Pruritus; Severity of Illness Index; Treatment Outcome; Young Adult

Topics: Humans; Ichthyosiform Erythroderma, Congenital; Ichthyosis, Lamellar; Isotretinoin

Topics: Genes, Recessive; Humans; Ichthyosis, Lamellar; Isotretinoin

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.

Topics: Administration, Cutaneous; Adolescent; Adult; Antibodies, Monoclonal; Darier Disease; Double-Blind Method; Female; Humans; Ichthyosis, Lamellar; Immunoenzyme Techniques; Isotretinoin; Keratins; Male

Consanguinity is known to be associated with an increase in the prevalence of autosomal recessive disorders such as autosomal recessive congenital ichthyosis (ARCI). ARCI often responds well to retinoid treatment. We describe a patient with ARCI who improved under isotretinoin treatment. The patient subsequently developed elevated levels of serum creatinine phosphokinase (CPK), which led to the diagnosis of a second autosomal recessive disorder, dysferlinopathy, a rare myopathy characterized by muscle weakness, decreased tendon reflexes and marked elevation of CPK levels. This report demonstrates the need for physicians to remain alert to the possible coexistence of rare and mutually relevant disorders in populations with a high rate of consanguinity.

Topics: Adolescent; Alanine Transaminase; Arabs; Aspartate Aminotransferases; Consanguinity; Creatine Kinase; Female; Genes, Recessive; Humans; Ichthyosiform Erythroderma, Congenital; Ichthyosis, Lamellar; Isotretinoin; Keratoderma, Palmoplantar; Muscular Dystrophies, Limb-Girdle; Myalgia

Harlequin ichthyosis is a rare congenital ichthyosis classified under the category of Autosomal Recessive Congenital Ichthyoses, which also include lamellar ichthyosis and congenital ichthyosiform erythroderma. It is caused by functional null mutations in the ABCA12 gene, a keratinocyte lipid transporter associated with lamellar granule formation. Patients have a classic clinical presentation at delivery and need neonatal intensive care treatment to maximize their chances of survival. Early oral retinoid therapy has been shown to increase survival in patients with harlequin ichthyosis, and we present a case of a 9-month-old male with this condition who has been treated with isotretinoin since day 7 of life.

Topics: Humans; Ichthyosis, Lamellar; Infant; Infant, Newborn; Isotretinoin; Keratolytic Agents; Male