Congenital Ichthyosis: An Overview of Current and Emerging Therapies

Abstract

Congenital ichthyosis is a collective name for a group of monogenetic disorders of cornification, sometimes associated with systemic symptoms. There may be an abnormal quality or quantity of scale produced, abnormal thickness of stratum corneum or abnormal keratinocyte kinetics, often associated with skin inflammation. Pruritus, skin fragility, ectropion and anhidrosis are sometimes associated with the rare types of ichthyosis. Three important mechanisms are involved in the action of topical agents used in the treatment of ichthyosis: hydration, lubrication and keratolysis. The latter effect can also be achieved with systemic retinoids. For ichthyosis with an increased tendency towards skin infections, antimicrobials are another group of widely used agents. Considering that patients with ichthyosis are potential mega-users of topical therapy, with an estimated lifetime consumption of approximately one tonne cream per capita, surprisingly few controlled trials of the various treatments have been performed. Moreover, nearly all therapeutic principles were established long before the recent increase in knowledge about the aetiology and pathophysiology of ichthyosis. This calls for new ideas and intensified efforts to develop future ichthyosis therapies.

Revised nomenclature and classification of inherited ichthyoses: Results of the First Ichthyosis Consensus Conference in Sorèze 2009

“…31,45 The phenotypes can change over time and in response to treatment, eg, LI treated with oral retinoids can evolve into an erythrodermic ichthyosis with a finer scale pattern. 46 In a recent North American study of 104 patients with non-HI ARCI, mutations in TGM1 were significantly associated with collodion membrane, ectropion, platelike scales, and alopecia. Patients who had at least one mutation predicted to truncate TGase-1 were more likely to have severe hypohidrosis and overheating than those with TGM1 missense mutations only.…”

“…6,35,46,[229][230][231][232] Importantly, clinicians have to consider the functional consequences of the epidermal barrier defect, such as increased risk of systemic absorption and toxicity, especially in infants. [231][232][233] Neonates with severe congenital phenotypes may require intensive care using humidified isolettes (incubators) to avoid temperature instability and hypernatremic dehydration, and observation for signs of cutaneous infection and septicemia.…”

Inherited ichthyoses/generalized Mendelian disorders of cornification

“…81,82 Instead, therapy of MeDOC is symptomatic and mostly based on patient's experiences rather than disease pathogenesis. Often patients are experts in their individual needs and the role of the physician is to provide guidance on general treatment principals and information about potential interactions and adverse effects.…”

A Roadmap for Fever of Unknown Origin in Children

“…A persistent fever combined with diffuse vasculitic lesions can be related to serum sickness, a type III hypersensitivity-mediated reaction, appearing 1-3 weeks after the injection of different polyclonal antibodies or non-protein drugs in immunocompromised children (45). Congenital ichthyosis, a rare disease characterized by varying degrees of skin scaling and abnormal epidermis differentiation, can be sometimes associated with persisting fevers, regarded as FUO (46).…”