Last Updated: 2023-10-12
Author(s): Lindemann H.
ICD11: Q80.8
The term "autosomal recessive congenital ichthyoses" (ARCI) was introduced by Oji V et al. 2009.
ARCI; Autosomal recessive congenital ichthyoses; Erythrodermic lamellar ichthyosis; Collodion baby; Congenital autosomal recessive ichthyoses; Ichthyosis congenita; Lamellar ichthyosis and congenital ichthyosiform erythroderma; Congenital autosomal recessive (non-syndromal, non-bullous) ichthyoses; Non-bullous congenital ichthyosiform erythroderma; Non-bullous lamellar ichthyosis
It is a group of autosomal recessive congenital cornification disorders of the skin that have existed since birth. The diseases differ from each other in their clinic, genetics and molecular biology. In the past, the diseases were grouped together under the name "ichthyosis congenita" and differentiated into severity grades (I - III) on the basis of the clinic. Today, the diseases are classified according to their molecular genetics.
The ARCI are typically non-syndromal. The malformation syndromes are confined exclusively to the skin.
Overall incidence of ARCI circa 1:60,000.
Self-healing congenital ichthyosis (SICI): <1:1,000,000
Lammular ichthyosis (LI):1:200,000 / 300,000
Congential ichthoysiform erythroderma (CIE): 1:100,000 / 200,000
Swimsuit ichthyosis: <1:1,000,000
Harlequin ichthyosis: <1:1,000,000
The ARCI group includes:
SICI (Q80.2):
Mutation: TGM1. Abbreviation: ARCI1. OMIM: 242300.
Mutation: ALOXE12B. Identifier: ARCI2. OMIM: 242100.
Mutation: ALOXE3. Abbreviation: ARCI3. OMIM: 606545.
LI (Q80.2) / CIE (Q80.2). As well as the intermediate phenotypes of LI and CIE:
Mutation: TGM1. Abbreviation: ARCI1. OMIM: 242300.
Mutation: ALOXE12B. Identifier: ARCI2. OMIM: 242100.
Mutation: ALOXE3. Abbreviation: ARCI3. OMIM: 242100.
Mutation: ABCA12. Abbreviation: ARCI4A. OMIM: 60127.
Mutation: CYP4F22. Abbreviation: ARCI 5. OMIM: 664777.
Mutation: NIPAL4. Abbreviation: ARCI 6. OMIM: 612281.
Mutation: LIPN. Abbreviation: ARCI 8. OMIM: 613943.
Mutation: CERS3. Abbreviation: ARCI 9. OMIM: 615023.
Mutation: PNPLA1. Identifier: ARCI 10. OMIM: 615024.
Mutation: ST14. Abbreviation: ARCI 11. OMIM: 602400.
Mutation: CASP14. Abbreviation: ARCI 12. OMIM: 617320.
Swimsuit ichthyosis (Q80.2):
Mutation: TGM1. Abbreviation: ARCI3. OMIM: 242300.
Harlequin ichthyosis (Q80.4):
Mutation: ABCA12. Abbreviation: ARCI4B. OMIM: 242500.
ARCI results from a disorder of terminal differentiation of the epidermis. Mutations in the transglutaminase-1 gene (35 - 40% of cases) can be detected most frequently. Transglutaminase-1 contributes decisively to the development of the stratum corneum and to the postnatal adaptation of the skin through the formation of cornified cell envelopes.
Other mutations that can cause ARCI are:
ABCA12, a fat transport protein.
ALOXE3 and ALOX12B, lipoxygenases of the epidermis.
CYP4F22, a cytochrome P-450 oxidase.
CERS3, a ceramide synthetase that influences the ceramide balance of the skin.
The clinic of ARCI is very heterogeneous. Apart from harlequin ichthyosis, collodion membrane can often be observed at birth in ARCI.
In the clinical course, the collodion membrane detaches. An ichthyotic skin appearance remains. The skin may itch and hurt. Sensitivity may be reduced due to the scales.
SICI: This is a special case. After spontaneous detachment of the collodion membrane after 2 - 4 weeks, an almost ichthyosis-free skin presents.
LI: LI denotes a phenotype and not a separate entity. This can occur in all forms of ARCI. The scaling is classically large, squamous and dark. However, milder forms with lighter thinner scales are also known. There is heat intolerance. Scarring alopecia, ectropion and eclabium are common.
CIE: There is a fine white overlying scaling. Erythroderma is characteristic of CIE. Painful fissures, digital contractions and nail dystrophies are often seen. The clinical manifestations can vary in severity. There is heat intolerance. There may be scarring alopecia. Ectropion may also sometimes occur.
LI/CIE: Intermediate phenotypes are often observed.
Bathing-train ichthyosis: The temperature-sensitive mutation in the transglutaminase 1 gene causes healing of skin lesions in areas that are cooled. Typically, these are arms, legs and the face. More central parts of the body (which are normally covered by a swimming costume), on the other hand, are more severely affected.
Harlequin ichthyosis: Clinically, a severe cornification disorder with thickened skin is seen. There are geometric deep fissures of the skin. Often almost the entire body of the newborn is affected. Respiratory and feeding difficulties may develop. The risk of neonatal sepsis often leads to neonatal deaths. Survivors often develop a phenotype similar to CIE.
The diagnosis is made via the clinic (infestation pattern) and the determination of the genotype. A molecular genetic diagnosis is made from the blood.
Generalised skin lesions.
Dermatopathology shows no changes specific to the ARCI forms of the disease.
Frequently, however, compared to LI, parakeratosis and epidermal cell turnover rate may appear more marked in CIE.
The prognosis depends on the severity of the skin lesions.
In the neonatal period, sepsis and disturbances of the water and electrolyte balance may occur. During life, the disease usually remains stable. There is a normal life expectancy. ARCI has a considerable impact on the quality of life due to the limitations caused by the disease and treatment and the external appearance. Due to severe skin changes and eye complications, there may be delayed milestones in motor and social development.
Harlequin ichthyosis: There is significant morbidity and mortality shortly after birth. Survivors often develop a phenotype similar to CIE and have a normal life expectancy.
The therapy depends on the severity of the skin changes. In particular, keratolytic and moisturising topical preparations are used. Good results can be achieved with 5-10% urea, possibly 10% lactic acid or acetylcysteine in ointment base R003 . While external retinoids often cause irritation, low-dose systemic retinoids can improve skin appearance. In adults, 10 - 35 mg/day acitretin p.o. can be used initially. A maintenance dose as low as possible is to be aimed for.
ARCI is often associated with ectropion. In this case, the eyes should be treated separately.
Harlequin ectropion:The severity of the skin lesion may necessitate intensive medical care. Positioning in humidified incubators, balancing water and electrolyte balance and avoiding secondary infections reduces mortality and morbidity in the neonatal period.
