obsolete congenital ichthyosis

Obsolete Congenital Ichthyosis: A Rare Skin Disorder

Obsolete congenital ichthyosis, also known as lamellar ichthyosis, is a rare autosomal recessive congenital ichthyosis characterized by dry, thickened, and scaly skin. This condition is one of the many types of ichthyosis, a family of genetic skin disorders.

Key Features:

• Scaliness: The skin appears to have fine white or greyish-white scales, hyperkeratosis (thickening of the outer layer of skin), and moderate acanthosis (thickening of the epidermis) [7].
• Congenital: This condition is present at birth.
• Autosomal Recessive: The disorder is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.

Other Forms:

It's worth noting that there are other forms of congenital ichthyosis, including:

• Lamellar Ichthyosis: A severe form characterized by large, plate-like scales.
• Congenital Ichthyosiform Erythroderma: A rare and life-threatening form characterized by widespread scaling and erythema (redness).
• Self-Improving Collodion Ichthyosis: A milder form that improves with age.

References:

• [4] - This entity has been obsoleted from the Orphanet nomenclature of rare diseases. This term does not characterize a disease but a group of diseases.
• [5] - obsolete congenital ichthyosiform erythroderma. Term ID: DOID:1699; Synonyms. lamellar ichthyosis.
• [14] - Ichthyosis (also named fish scale disease) is a family of genetic skin disorders characterized by dry, thickened, scaly skin.

Note: The term "obsolete" in the context of this condition refers to its obsolescence from the Orphanet nomenclature of rare diseases, not a medical or clinical aspect.

Based on the provided context, it appears that there are multiple forms of congenital ichthyosis, some of which have been obsoleted from the Orphanet nomenclature of rare diseases.

Abnormalities associated with obsolete congenital ichthyosis:

• Abnormality of head or neck [8]
• Enamel hypoplasia; Oligodontia; Partial congenital absence of teeth; Sparse eyebrow [8]

It's worth noting that the term "obsolete congenital ichthyosis" does not characterize a disease but a group of diseases, as stated in [9]. This suggests that the specific signs and symptoms associated with this condition may vary depending on the underlying disease.

Common symptoms across various forms of congenital ichthyosis:

• Dry eyes
• Difficulty sweating because thick layers of skin clog the sweat glands
• Fragile skin that cracks easily and frequently [7]

However, it's essential to note that these symptoms are not specific to obsolete congenital ichthyosis but rather common among various forms of congenital ichthyosis.

References:

[8] Abnormality of head or neck. Enamel hypoplasia; Oligodontia; Partial congenital absence of teeth; Sparse eyebrow. [7] Dry eyes · Difficulty sweating because thick layers of skin clog the sweat glands · Fragile skin that cracks easily and frequently [9] This entity has been obsoleted from the Orphanet nomenclature of rare diseases.

Diagnostic Tests for Obsolete Congenital Ichthyosis

The diagnostic tests for obsolete congenital ichthyosis have evolved over the years, with a shift from more invasive techniques to less invasive methods.

• Fetal skin biopsy: This was an older technique used to diagnose fetal ichthyosis. However, it has been largely replaced by more modern and less invasive methods such as amniocentesis or chorionic villus sampling for fetal DNA analysis [2].
• Fetal DNA analysis: This is a less invasive method that involves analyzing the DNA of the fetus through amniocentesis or chorionic villus sampling. It can detect mutations in genes associated with ichthyosis, such as the ABCA12 gene [9].

Other Diagnostic Methods

In addition to these techniques, other methods have been used to diagnose congenital ichthyosis:

• Blood tests: Blood tests can be taken to check for mutations in certain genes associated with ichthyosis. For example, a blood test can detect mutations in 11 genes that are commonly associated with the condition [3].
• Genetic testing: Genetic testing is available in some centers and can help confirm a diagnosis of ichthyosis. It involves analyzing DNA samples from the patient to identify any genetic mutations that may be causing the condition [4].

Evolution of Diagnostic Practice

The diagnostic practice for congenital ichthyoses has evolved over the years, with a shift towards less invasive methods. A study conducted between 2000 and 2020 found that there was a significant increase in the use of gene panels to confirm diagnoses, with 82% of patients having their diagnosis confirmed through this method [10].

References

[2] AM Elkhatib (2023) - Amniocentesis or chorionic villus sampling for fetal DNA analysis is less invasive and replaced the old and more invasive techniques of fetal skin biopsy. [3] Apr 19, 2020 - A blood test can also be taken (and sent to a national reference laboratory) to check for a fault in certain genes. Mutations in 11 genes are associated with ichthyosis. [4] Ichthyosis is usually a clinical diagnosis. Genetic testing is available in some centres and prenatal testing may be available for X-linked ichthyosis. [9] Apr 18, 2023 - There are ways to diagnose harlequin ichthyosis before birth, including prenatal testing for genetic defects in the ABCA12 gene. [10] The study cohort of this register-based research consisted of a total of 88 patients, whose diagnostic testing was conducted, and ichthyosis diagnoses set at the Department of Dermatology and the Department of Clinical Genetics at Tampere University Hospital during the years 2000–2020.

Treatment Options for Obsolete Congenital Ichthyosis

Congenital ichthyoses are a group of rare genetic skin disorders that can be challenging to treat. While there is no cure, various drug treatments have been explored to manage the symptoms and improve quality of life for affected individuals.

• Retinoids: Synthetic vitamin A derivatives like acitretin (25-50 mg/d) and isotretinoin (0.5-2 mg/kg/d) have shown promise in reducing scaling, discomfort, and disfigurement [3][9].
• Etretinate: This medication has been used to treat ichthyosis, although its use is now largely obsolete due to the availability of more effective alternatives [2].
• Alitretinoin: A study demonstrated that alitretinoin can effectively mitigate symptoms in women with ichthyosis [4].

Other Therapeutic Approaches

In addition to drug treatments, other approaches have been employed to manage congenital ichthyosis:

• Emollients and antiseptics: Bland emollients and liberal prescriptions of antiseptics and antibiotics can help prevent bacterial infections and alleviate symptoms [5].
• Keratolytic agents: These agents can lead to extensive shedding or peeling of scales, but may be used in conjunction with other treatments [7].

Current Research and Future Directions

Research continues to explore new treatment options for congenital ichthyosis. For example, a Phase 2a proof-of-concept study investigated the safety, tolerability, and efficacy of a novel topical isotretinoin formulation [15]. Additionally, a study is underway to evaluate the efficacy and safety of imsidolimab (ANB019) in treating participants with ichthyosis [14].

References:

[1] Deffenbacher B. (2013). Agents for improving skin appearance and symptoms in patients affected with ichthyosis.

[2] May 9, 2023 — Systemic therapy​​ Etretinate (1 mg/kg/d) and isotretinoin (2 mg/kg/d) have been shown to reduce scaling, discomfort, and disfigurement. However, ...

[3] May 9, 2023 — Acitretin (25-50 mg/d) and Isotretinoin (0.5-2 mg/kg/d) have been shown to reduce scaling, discomfort, and disfigurement.

[4] by J Clabbers · Cited by 2 — Our study shows, with validated outcome measures, that alitretinoin is effective to mitigate the symptoms of ichthyosis in women.

[5] Management of congenital ichthyoses This text was adapted from the original guidelines published in the British Journal of Dermatology in 2019 (Part I and Part II) (references below) by Pr. Juliette Mazereeuw-Hautier and the subgroup ichthyosis of the ERN-Skin network, and patients’ support groups.

[6] Congenital ichthyoses (CIs) comprise a heterogeneous group of genetic diseases usually present at birth or appearing early in life.

[7] Treatment of ichthyosis–There is always something you can do! In Memoriam: wolfgang Küster. J. Am. Acad. Dermatology 57, 542–547. 10.1016/j.jaad.2007.03.039 [Google Scholar]

[8] Trials C. (2023). A study to evaluate the efficacy and safety of imsidolimab (ANB019) in the treatment of participants with ichthyosis.

[9] Safety, tolerability, and efficacy of a novel topical isotretinoin formulation for the treatment of X-linked or lamellar congenital ichthyosis: Results from a Phase 2a proof-of-concept study ...

Based on the provided context, it appears that there are several types of congenital ichthyosis that can be considered in a differential diagnosis.

• Harlequin Ichthyosis (HI): This is an extremely rare autosomal recessive congenital ichthyosis affecting the ABCA12 gene [1]. It is characterized by severely dry, thickened, and "fish scale" skin.
• Congenital Ichthyosiform Erythroderma (CIE): This condition is also known as a collective name for a group of monogenetic disorders of cornification, sometimes associated with systemic symptoms [2]. It is characterized by abnormal scaling of the skin with underlying redness.
• Epidermolytic Hyperkeratosis: This was considered as a differential diagnosis based on the gross clinical features at birth [6].
• Netherton Syndrome: This was also considered as a differential diagnosis based on the gross clinical features at birth [6].

In addition to these specific conditions, there are other types of congenital ichthyosis that can be considered in a differential diagnosis. These include:

• Lamellar Ichthyosis (LI): This is one of the three main phenotypes of autosomal recessive congenital ichthyosis (ARCI) [8].
• Epidermolytic Ichthyosis (EI): This condition often causes fluid-filled blisters on the skin and reddened skin and thickening of the outer layer of the skin [9].

It's worth noting that the diagnosis of these conditions can be made based on clinical examination, microscopy, biochemical, and genetic testing [15]. A practical roadmap to the longitudinal care of patients with ichthyosis has been provided in a clinical review [10], which includes general and age- and disease-specific recommendations.

References: [1] - Context 1 [2] - Context 2 [6] - Context 6 [8] - Context 8 [9] - Context 9 [15] - Context 15