Materiały źródłowe

• #1 Role of molecular testing in the multidisciplinary diagnostic approach of ichthyosis | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-016-0384-4

  The term ichthyosis describes a generalized disorder of cornification characterized by scaling and/or hyperkeratosis of different skin regions. […] In this setting, the diagnosis of ichthyosis is an integrated multistep process requiring a multidisciplinary approach in order to formulate the appropriate diagnostic hypothesis and to address the genetic testing. […] Ichthyosis diagnosis requires a multidisciplinary approach, coordinated by a dermatologist, in order to correlate the clinical features, the microscopic and laboratory data and to formulate a diagnostic hypothesis; the final diagnosis is generally established through molecular testing. […] Currently, molecular diagnosis of congenital and syndromic ichthyoses is a very hard challenge due to the high number of genes involved.

• #1 Ichthyosis vulgaris: Diagnosis and treatment

  https://www.aad.org/public/diseases/a-z/ichthyosis-vulgaris-treatment

  A dermatologist can often diagnose ichthyosis vulgaris by looking at a patients skin. […] Sometimes, ichthyosis vulgaris looks like another skin condition. If this happens, your dermatologist can remove a small amount of skin so that it can be looked at under a microscope. This is called a skin biopsy. Your dermatologist can quickly and easily remove the skin during an appointment. […] There is no cure for inherited ichthyosis vulgaris. Treatment focuses on reducing the scale and dry skin. […] If the ichthyosis is severe and fails to improve with baths, moisturizer, and scale remover, your dermatologist can prescribe medicine. […] For people who have the inherited type, the outlook is excellent. Most have a normal lifespan. Ichthyosis vulgaris also can become less serious with age. Most people, however, need to continue treating their skin for life. […] To improve acquired ichthyosis vulgaris, you must also treat the disease that triggered the ichthyosis. If the disease can be cured, the ichthyosis may go away. If a medicine triggered the ichthyosis, reducing the dose often gets rid of the ichthyosis.

• #1 Ichthyosis: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1198130-overview

  Ichthyosis refers to a relatively uncommon group of skin disorders characterized by the presence of excessive amounts of dry surface scales. It is regarded as a disorder of keratinization or cornification, and it is due to abnormal epidermal differentiation or metabolism. […] The ichthyosiform dermatoses may be classified according to clinical manifestations, genetic presentation, and histologic findings. Inherited and acquired forms of ichthyosis have been described, and ocular alterations may occur in specific subtypes. […] Ichthyosis vulgaris is characterized by onset in early childhood, usually between age 3 and 12 months, with fine scales and varying degrees of dryness of the skin. […] An association may be present between ichthyosis vulgaris and atopic diseases because one third to one half of patients show features of atopic disease and a similar proportion have relatives with atopic disease.

• #1 Ichthyosis Vulgaris: Causes, Symptoms, Treatment & Recovery

  https://my.clevelandclinic.org/health/diseases/21069-ichthyosis-vulgaris

  Ichthyosis vulgaris can be difficult to diagnose. Many people with mild cases often assume they just have dry skin. If moisturizers dont help, you may have ichthyosis vulgaris. […] A healthcare provider like a dermatologist can diagnose the condition by discussing your symptoms. Theyll examine your skin and ask what makes the symptoms better or worse. Theyll also ask about your familys history of skin conditions and any medications youre taking. […] Ichthyosis vulgaris is usually a clinical diagnosis that doesnt require testing. But a healthcare provider may order a skin biopsy to look at a skin sample under a microscope. Or they may order a blood test or saliva test to look for a filaggrin mutation.

• #1 Ichthyosis Workup: Laboratory Studies, Imaging Studies, Other Tests

  https://emedicine.medscape.com/article/1198130-workup

  Prenatal diagnosis of lamellar ichthyosis can be made by direct mutational analysis of the keratinocyte transglutaminase gene. […] Fetal skin biopsy that examines keratinized hair canals and amniotic fluid at approximately 19 weeks estimated gestation age may provide an early diagnosis of certain forms of ichthyosis (ie, Harlequin type, which is extremely severe and usually fatal). […] In ichthyosis vulgaris, the affected skin displays mild hyperkeratosis and a diminished granular layer in the epidermis, while the dermis has normal features. […] Affected skin in X-linked ichthyosis shows an expanded stratum corneum without parakeratosis or acanthosis. […] Lamellar ichthyosis displays massive, compact orthohyperkeratosis with variable degrees of parakeratosis and a markedly thick stratum corneum. […] In epidermolytic hyperkeratosis, the skin biopsy specimen shows epidermal acanthosis and hyperkeratosis. […] The skin biopsy specimen from patients with congenital ichthyosiform erythroderma (CIE) shows compact hyperkeratosis and moderate increase in stratum corneum thickness.

• #1 Ichthyosis – Dermatologic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/dermatologic-disorders/cornification-disorders/ichthyosis

  Ichthyosis is scaling and flaking of skin ranging from mild but annoying dryness to severe disfiguring disease. Diagnosis is clinical. […] Diagnosis is based on clinical evaluation including dermatologic features, age of onset, family history, and evidence of an associated or underlying disorder. […] Genetic testing is useful in establishing or confirming specific types of ichthyosis and in genetic counseling. […] A dermatologist should assist in diagnosis and management, and a medical geneticist should be consulted for genetic counseling.

• #1 Ichthyosis Workup: Laboratory Studies, Imaging Studies, Other Tests

  https://emedicine.medscape.com/article/1198130-workup

  In some congenital ichthyosiform disorders, routine histopathology, electron microscopy, and frozen sections of skin biopsy specimens may be required to determine the specific classification of disease. […] Tests that may be required to diagnose the type of ichthyosis may include the following: Ichthyosis vulgaris – Skin biopsy […] X-linked recessive ichthyosis Steroid sulfatase (STS) activity or levels of cholesterol sulfate and genetic testing of amniotic fluid for partial or complete deletion of the STS gene mapped on band Xp22.3 […] Epidermolytic hyperkeratosis – Skin biopsy and keratin gene studies […] Lamellar ichthyosis Genetic analysis for mutations in the gene for transglutaminase 1, leading to greatly reduced skin transglutaminase activity by radiometric assay […] CHILD syndrome – Radiographic and molecular genetic studies for mutations in an essential enzyme of cholesterol biosynthesis, NADPH steroid dehydrogenase

• #1 Role of molecular testing in the multidisciplinary diagnostic approach of ichthyosis | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-016-0384-4

  Our goal is to validate a multidisciplinary approach and to improve diagnostic accuracy in patients with ichthyosis achieving the identification of the mutation responsible for the disease. […] The genetic diagnosis of ichthyosis leads to a more accurate and effective genetic counseling, allowing correct evaluation of the risk of recurrence, particularly in families with consanguineous background. […] In our experience this is underlined by the possibility of having inconsistencies between the clinical appearance and histopathology and by the detection in about half the cases of new genetic variants that are not described in the literature. […] Therefore, a careful clinical selection of cases and a pathologic/clinical comparison are essential in order to guide the identification of the genetic mutation that today represents the diagnostic gold standard. […] Nowadays is available a new innovative technology, NGS, that is more powerful, fast and economic and allows to more easily obtain genetic diagnosis.

• #1 Comprehensive Molecular Analysis of Disease-Related Genes as First-Tier Test for Early Diagnosis, Classification, and Management of Patients Affected by Nonsyndromic Ichthyosis

  https://www.mdpi.com/2227-9059/12/5/1112

  Comprehensive Molecular Analysis of Disease-Related Genes as First-Tier Test for Early Diagnosis, Classification, and Management of Patients Affected by Nonsyndromic Ichthyosis […] Inherited ichthyoses are a group of clinically and genetically heterogeneous rare disorders of skin keratinization with overlapping phenotypes. The clinical picture and family history are crucial to formulating the diagnostic hypothesis, but only the identification of the genetic defect allows the correct classification. […] However, clinical and genetic classification of ichthyosis is important to identify possible associated diseases in syndromic forms, for genetic counseling and prenatal diagnosis, to follow the clinical course of the disease, and to start potential therapies. […] Clinical evaluation, histological and electron microscopy analysis, as well as family history are important clues for the classification of an ichthyosis form, but the correct and definitive diagnosis can be obtained when DNA analysis identifies the molecular cause of the disease. Due to the wide genetic heterogeneity, molecular analysis of multiple genes by next-generation sequencing (NGS) technology represents the most sensitive methodology to obtain the diagnosis in the greatest number of affected patients. […] In the attempt to identify the genetic cause of the disease in 17 unrelated Italian patients referred with nonsyndromic congenital ichthyosis, without having any further details regarding family history or phenotypic features, we performed an NGS analysis focused on a panel of over 50 genes that covers most forms of isolate and syndromic ichthyosis, including XLI and IV. […] In our cohort of 17 unrelated probands with congenital ichthyosis, multigene NGS analysis allowed the molecular classification of all the referred cases. The high success rate of our methodology was mostly due to a data analysis strategy that, in addition to known and new disease-causing SNVs, was able to reveal heterozygous and hemizygous large deletions, therefore confirming elevated sensitivity also for the detection of these types of CNV. […] Multigene NGS analysis is the method of choice for the comprehensive molecular testing and early classification of patients affected by any type of ichthyosis, including XLI and IV. Indeed, we herein demonstrate that targeted quantitative analysis of NGS data of a specific gene, by identifying heterozygous and homo/hemizygous CNVs, partly resolves missing heritability problem, therefore improving diagnostic sensitivity of the whole procedure, with useful implications for clinical practice.

• #1 Ichthyosis Vulgaris Diagnosis | AccessMedicine Network

  https://www.accessmedicinenetwork.com/posts/49898-ichthyosis-vulgaris-diagnosis

  Ichthyosis vulgaris is by far the most common form of ichthyosis and results from mutations in FLG, the gene encoding filaggrin. Regardless of severity, the onset of scaling in ichthyosis vulgaris tends to occur after 2 to 3 months of age (not at birth) and may become more prominent during childhood or adolescence. Fine, white scales, often without much erythema, predominate on the exterior surfaces of the extremities, especially the legs. The scaling of patients with ichthyosis vulgaris is most severe on the lower extremities and during cold months. The palms and soles tend to be mildly thickened as well in this semi-dominant common skin disorder. […] Source: Kline MW. Rudolph’s Pediatrics, 23e; 2018.

• #1 Ichthyosis Vulgaris – UtahDERM Diagnoses

  https://utahderm.med.utah.edu/diagnoses/ichthyosis-vulgaris/

  Ichthyosis is an umbrella term for a group of scaling disorders caused by a poorly formed skin barrier. Inherited ichthyosis can be syndromic, but is most often non-syndromic and limited to the skin. Ichthyosis vulgaris (IV) is the most common non-syndromic form. IV is inherited in an autosomal dominant pattern and is caused by a filaggrin (FLG) gene mutation. Diagnosis can be made based on clinical presentation and a positive family history of IV. In most cases, clinical diagnosis is adequate and additional diagnostic testing is not necessary. If the diagnosis is not apparent on clinical exam and history, a skin biopsy can help confirm. Histology reveals orthohyperkeratosis of the stratum corneum and a decreased or absent granular layer. […] There is no cure for IV so the primary goal is to hydrate skin and remove excess scale while preventing infection and irritation.

• #1 X-linked ichthyosis – UpToDate

  https://www.uptodate.com/contents/x-linked-ichthyosis

  X-linked ichthyosis (XLI; MIM #308100), also called steroid sulfatase (STS) deficiency, is caused by deletions or pathogenic variants in the STS gene (encoding the STS enzyme) and is generally considered nonsyndromic. […] The disease presents at birth or in early infancy with dry skin and a tendency to form scales on the extremities and trunk. Along with ichthyosis vulgaris, the skin phenotype of XLI tends to be milder than most other hereditary forms of ichthyosis. […] This topic will review the clinical features, diagnosis, and management of XLI.

• #1 Ichthyosis: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1198130-overview

  Lamellar ichthyosis is a rare, autosomal recessive, genetically heterogeneous skin disease caused by mutations involving multiple genetic loci. […] In X-linked ichthyosis, generalized scaling is present at or shortly after birth. […] Irregular stromal corneal opacities that are located anterior to the Descemet membrane are found in 16-50% of male patients, and this finding may be used to distinguish this form of ichthyosis from all other forms. […] Approximately 25% of female carriers have minor corneal opacities. […] An example of findings in X-linked ichthyosis is shown in the image below. […] Previous studies have shown a deficiency of steroid sulfatase (STS) in skin fibroblasts and a marked elevation of plasma cholesterol sulfate in patients with X-linked ichthyosis. […] Acquired ichthyosis usually occurs in adults and manifests as small, white, fishlike scales that frequently are concentrated on the extremities but may be seen in a generalized distribution.

• #1 Orphanet: Lamellar ichthyosis

  https://www.orpha.net/en/disease/detail/313

  A rare autosomal recessive congenital ichthyosis characterized by the presence of large scales all over the body without significant erythroderma. […] The diagnosis is based on the clinical appearance of the skin and can be confirmed by genetic testing. […] Histological features include orthohyperkeratosis, a normal to slightly widened stratum granulosum, acanthosis, and papillomatosis of the epidermis. […] Immunohistochemistry using antibodies directed against transglutaminase 1 or transglutaminase 1 enzyme activity measurement is available in some centers. […] Molecular testing (such as gene panel diagnosis) is possible in national reference laboratories. […] Prenatal diagnosis is based on DNA analysis of amniocentesis and chorion villus sampling materials. […] Genetic counseling should be offered to the affected families.

• #1 Lamellar Ichthyosis (autosomal recessive congenital ichthyosis, ARCI) – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/lamellar-ichthyosis-autosomal-recessive-congenital-ichthyosis-arci/

  Lamellar ichthyosis (LI) most often presents in the newborn period as a collodion baby with pronounced ectropion and eclabium. […] The diagnosis of LI is usually made on clinical grounds. […] The main differential diagnosis is CIE and, given that they are caused by the same group of genetic defects, they may be a spectrum of disease rather than specific entities. […] There are six known genes that lead to the LI phenotype, and commercial testing is available but expensive. […] Genetic counseling should be offered to all patients and families. […] The risks associated with future pregnancies and the availability of genetic testing should be clearly and expertly explained. […] Prenatal diagnosis and preimplantation genetic diagnosis for at-risk pregnancies can be performed but require prior identification of the disease-causing mutations in the family.

• #1 Prenatal diagnosis of harlequin ichthyosis by ultrasonography: a case report

  https://atm.amegroups.org/article/view/61339/html

  Autosomal recessive congenital ichthyosis is a genetically and phenotypically heterogeneous group of skin disorders, including harlequin ichthyosis (HI), lamellar ichthyosis, and bullous congenital ichthyosiform erythroderma. […] HI is the most phenotypically severe autosomal recessive congenital ichthyosis associated with the mutation of the adenosine triphosphatebinding cassette subfamily A member 12 (ABCA12) gene. […] However, the severe HI may easily be misdiagnosed as epidermolysis bullosa or syndromic ichthyosis. […] Until the ABCA12 gene was identified as the pathogenic gene, prenatal diagnosis of HI had been performed by the invasive techniques of fetal skin biopsy. Now, advances in ultrasound technology and fetal DNA-based analysis have replaced it. […] The mortality rate is markedly high and prompt; prenatal diagnosis of neonate HI is critical for appropriate perinatal and postnatal management.

• #1 Prenatal diagnosis of harlequin ichthyosis. Case report

  http://www.scielo.org.pe/scielo.php?script=sci_arttext&pid=S2304-51322023000300013&lng=en&nrm=iso&tlng=en

  Prenatal diagnosis of harlequin ichthyosis. Case report […] Harlequin ichthyosis, also known as diffuse fetal keratosis, is an extremely rare and phenotypically severe hereditary skin disorder with autosomal recessive inheritance. This disease is caused by mutations in the adenosine triphosphate-binding cassette transporter protein (ABCA12) gene. Prenatal ultrasonography and genetic analysis are important for prenatal diagnosis. Prenatal ultrasonographic diagnosis is difficult, and findings include ectropion plates, an abnormal auricular pinna, a flat nose, thickened skin with an armor-like appearance, thickened lips with sustained open mouth (fish mouth) status, and flexion fixation of the extremities. These are usually found during the third trimester. Three-dimensional ultrasonography contributes to the evaluation of facial morphology. The prognosis is generally poor. Affected neonates usually do not survive beyond the first days of life. A case of prenatal diagnosis of harlequin ichthyosis is presented.

• #1 Prenatal diagnosis of harlequin ichthyosis. Case report

  http://www.scielo.org.pe/scielo.php?script=sci_arttext&pid=S2304-51322023000300013&lng=en&nrm=iso&tlng=en

  Ultrasonography and genetic analysis are useful tools for prenatal diagnosis. […] Diagnosis is based on identifying ABCA12 mutations. […] The diagnosis can be confirmed by chorionic villus sampling or amniotic fluid sampling. […] Prenatal genetic diagnosis should be advised for couples with previously affected children. Characteristic features on prenatal ultrasound tend to appear late, so evaluations should be repeated in the third trimester, even when the second trimester anatomic examination is normal.

• #1 Ichthyosis

  https://www.pcds.org.uk/clinical-guidance/ichthyosis

  The majority of patients will have an inherited ichthyosis, and depending on the type genetic testing may be needed. […] Patients with acquired ichthyosis require thorough investigation to look for an underlying cause, which includes: […] A more sudden onset of acquired ichthyosis similar to the pattern of ichthyosis vulgaris in adult life or with a generalized eczema craquel appearance suggests the possibility of internal malignancy, particularly if it occurs in a younger age group. […] The strongest association is with Hodgkin disease (accounting for over 70% of cases) and other lymphoreticular tumours, including T-cell lymphomas, leukaemias, myelodysplastic syndrome, multiple myeloma and polycythaemia vera. […] Cases linked with solid tumours are also well documented, including cancers of the ovary, kidney, liver and breast, as well as leiomyosarcoma.

• #1 Prenatal diagnosis of harlequin ichthyosis by ultrasonography: a case report

  https://atm.amegroups.org/article/view/61339/html

  A deep understanding of the HI genetic basis shows that genetic screening for candidate gene mutations associated with HI may aid in prenatal diagnosis. […] The first DNA-based prenatal diagnosis of HI was performed by direct sequence analysis of the ABCA12 mutation from amniotic fluid cells, which showed the effectiveness of early DNA-based prenatal diagnosis. […] In short, prenatal sonography and molecular diagnosis are increasingly feasible in patients with HI and are essential for giving correct genetic advice.

• #1 Prenatal diagnosis of a rare variant of harlequin ichthyosis with literature review | BMC Medical Imaging | Full Text

  https://bmcmedimaging.biomedcentral.com/articles/10.1186/s12880-021-00586-4

  In patients with family histories, fetoscopy with skin biopsy and ultrastructural examination of the hair canal and amniotic fluid cells may be helpful. […] For those without a family history, many cases are missed. […] Most of the characteristic features of ultrasound will only become apparent later in pregnancy when restricted skin development becomes a limitation to foetal growth and movements. […] In conclusion, HI can be easily detected by 2D ultrasound combined with 3D ultrasound, but attention should be paid to a systematic examination in the third trimester of pregnancy according to the clinical characteristics of the disease to avoid missing a diagnosis of HI, especially in cases without a family history.

• #1

  https://link.springer.com/article/10.1007/s40257-017-0313-x

  Hereditary ichthyoses are due to mutations on one or both alleles of more than 30 different genes, mainly expressed in the upper epidermis. […] A correct diagnosis of ichthyosis essential not only for genetic counseling but also for adequate patient information about prognosis and therapeutic options is becoming increasingly feasible thanks to recent progress in genetic knowledge and DNA sequencing methods. […] Given the conspicuous signs of widespread hyperkeratosis, scaling, xerosis, erythema, and occasional skin erosions, one may think that it is always easy to make a clinical diagnosis of ichthyosis and that patients seeking a doctor are likely to receive correct information about the disease and its treatment. In reality, however, the severe forms of ARCI and keratinopathic ichthyosis may easily be misdiagnosed as syndromic ichthyosis or epidermolysis bullosa (in neonates), and the milder forms as ichthyosis vulgaris (in older children and adults) or X-linked ichthyosis (in males), and vice versa.

• #1

  https://link.springer.com/article/10.1007/s40257-017-0313-x

  Routine skin histology is seldom of foremost value in the diagnosis of ichthyosis, except in ichthyosis vulgaris where an absence of the granular layer is suggestive, and in some forms of keratinopathic ichthyosis where epidermolysis occurs in the upper epidermis. […] For more than 30 years the gold standard for genetic analysis was the dideoxy sequencing (Sanger sequencing method; first generation) by which the coding part of the suspected disease-causing gene was analyzed, exon by exon. This was an expensive and time-consuming approach compared with the now available next generation (NGS) techniques. […] There are ichthyosis phenotypes with obvious clinical diagnosis in which the clinician can clearly assign a particular gene. But the remaining patients, especially those with mutations in ARCI genes, cannot be clearly distinguished from each other, even by very experienced clinicians. Therefore, the NGS methods such as multi-gene-panel sequencing that include all suspected candidate genes within one analysis are a perfect diagnostic approach.

• #1 Management of Ichthyosis: A Brief Review

  https://www.skintherapyletter.com/ichthyoses/management-ichthyosis-review/

  The majority of ichthyosis therapies aim to improve the barrier function of the skin. […] Patients diagnosed with ichthyosis should be aware of the lifelong course of this group of disorders, as there is currently no cure. […] Gene therapy is not yet a reality in ichthyosis therapy; however, genetic counseling remains an integral aspect of disease management. […] The ichthyoses are typically inherited conditions exhibiting disordered keratinization secondary to excessive transepidermal water loss, with the most common variants being ichthyosis vulgaris and X-linked recessive ichthyosis. […] Ichthyosis management requires a multimodal approach, including topical and oral agents in addition to lifestyle modifications.

• #1 Current Research Reveals New Treatment Options for Ichthyosis

  https://www.dermatologytimes.com/view/current-research-reveals-new-treatment-options-for-ichthyosis

  Genetic testing is a very important aspect in the diagnostic work-up of ichthyosis to better understand the pathophysiology of the disease and help clinicians arrive at the accurate diagnosis and appropriate management of patients skin disorders. […] An accurate molecular diagnosis is crucial for predicting prognosis and providing appropriate genetic counseling. […] According to Goldust, clinics and medical centers that provide genetic testing using whole-exome sequencing technology, which can investigate the many different genes responsible for ichthyosis, are paramount and requisite for complete patient care.

• #1 Ichtyoses – Therapeutics in Dermatology

  https://www.therapeutique-dermatologique.org/spip.php?article1683

  Ichthyosis is a disorder of cornification, as it results from a disturbance of the formation of the outermost skin barrier (stratum corneum). […] Dermatologists can often diagnose this disorder clinically, but a skin biopsy is usually performed to confirm the diagnosis and the type of ichthyosis. Further diagnostic work-up, including genetic testing, may be warranted. […] There is no cure for inherited ichthyoses. Severe disease forms, like collodion baby and harlequin baby, are life-threatening Dermatological emergencies requiring management in a neonatal intensive care unit, which includes placement in a high-humidity incubator, continuous clinical monitoring, nutritional and ventilatory support, careful skin care and prevention of infection. Treatment with systemic retinoids, like Acitretin and Isotretinoin, may be beneficial in severe forms. Vitamin D supplementation may be necessary in some cases. […] Every patient with suspected ichthyosis should see a Dermatologist for adequate diagnosis and treatment.

• #2 Ichtyoses – Therapeutics in Dermatology

  https://www.therapeutique-dermatologique.org/spip.php?article1683

  Ichthyosis is a disorder of cornification, as it results from a disturbance of the formation of the outermost skin barrier (stratum corneum). […] Dermatologists can often diagnose this disorder clinically, but a skin biopsy is usually performed to confirm the diagnosis and the type of ichthyosis. Further diagnostic work-up, including genetic testing, may be warranted. […] There is no cure for inherited ichthyoses. Severe disease forms, like collodion baby and harlequin baby, are life-threatening Dermatological emergencies requiring management in a neonatal intensive care unit, which includes placement in a high-humidity incubator, continuous clinical monitoring, nutritional and ventilatory support, careful skin care and prevention of infection. Treatment with systemic retinoids, like Acitretin and Isotretinoin, may be beneficial in severe forms. Vitamin D supplementation may be necessary in some cases. […] Every patient with suspected ichthyosis should see a Dermatologist for adequate diagnosis and treatment.

• #2 Ichthyosis – Dermatologic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/dermatologic-disorders/cornification-disorders/ichthyosis

  Ichthyosis is scaling and flaking of skin ranging from mild but annoying dryness to severe disfiguring disease. Diagnosis is clinical. […] Diagnosis is based on clinical evaluation including dermatologic features, age of onset, family history, and evidence of an associated or underlying disorder. […] Genetic testing is useful in establishing or confirming specific types of ichthyosis and in genetic counseling. […] A dermatologist should assist in diagnosis and management, and a medical geneticist should be consulted for genetic counseling.

• #2 Ichthyosis Vulgaris Diagnosis | AccessMedicine Network

  https://www.accessmedicinenetwork.com/posts/49898-ichthyosis-vulgaris-diagnosis

  Ichthyosis vulgaris is by far the most common form of ichthyosis and results from mutations in FLG, the gene encoding filaggrin. Regardless of severity, the onset of scaling in ichthyosis vulgaris tends to occur after 2 to 3 months of age (not at birth) and may become more prominent during childhood or adolescence. Fine, white scales, often without much erythema, predominate on the exterior surfaces of the extremities, especially the legs. The scaling of patients with ichthyosis vulgaris is most severe on the lower extremities and during cold months. The palms and soles tend to be mildly thickened as well in this semi-dominant common skin disorder. […] Source: Kline MW. Rudolph’s Pediatrics, 23e; 2018.

• #2 Ichthyosis vulgaris: Diagnosis and treatment

  https://www.aad.org/public/diseases/a-z/ichthyosis-vulgaris-treatment

  A dermatologist can often diagnose ichthyosis vulgaris by looking at a patients skin. […] Sometimes, ichthyosis vulgaris looks like another skin condition. If this happens, your dermatologist can remove a small amount of skin so that it can be looked at under a microscope. This is called a skin biopsy. Your dermatologist can quickly and easily remove the skin during an appointment. […] There is no cure for inherited ichthyosis vulgaris. Treatment focuses on reducing the scale and dry skin. […] If the ichthyosis is severe and fails to improve with baths, moisturizer, and scale remover, your dermatologist can prescribe medicine. […] For people who have the inherited type, the outlook is excellent. Most have a normal lifespan. Ichthyosis vulgaris also can become less serious with age. Most people, however, need to continue treating their skin for life. […] To improve acquired ichthyosis vulgaris, you must also treat the disease that triggered the ichthyosis. If the disease can be cured, the ichthyosis may go away. If a medicine triggered the ichthyosis, reducing the dose often gets rid of the ichthyosis.

• #2 Ichthyosis vulgaris

  https://dermnetnz.org/topics/ichthyosis-vulgaris

  Ichthyosis vulgaris is usually a clinical diagnosis. Mild ichthyosis is often just called 'dry skin’. […] Filaggrin mutations can be detected by research laboratories from a buccal smear or saliva sample. […] On skin biopsy, histology shows hyperkeratosis in the stratum corneum and reduced or absent granular layer. Electron microscopy also shows reduced or absent keratohyaline granules, of which the main component is the protein pro-filaggrin, the precursor to the filaggrin.

• #2 Role of molecular testing in the multidisciplinary diagnostic approach of ichthyosis | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-016-0384-4

  The term ichthyosis describes a generalized disorder of cornification characterized by scaling and/or hyperkeratosis of different skin regions. […] In this setting, the diagnosis of ichthyosis is an integrated multistep process requiring a multidisciplinary approach in order to formulate the appropriate diagnostic hypothesis and to address the genetic testing. […] Ichthyosis diagnosis requires a multidisciplinary approach, coordinated by a dermatologist, in order to correlate the clinical features, the microscopic and laboratory data and to formulate a diagnostic hypothesis; the final diagnosis is generally established through molecular testing. […] Currently, molecular diagnosis of congenital and syndromic ichthyoses is a very hard challenge due to the high number of genes involved.

• #2 Ichthyosis vulgaris – UpToDate

  https://www.uptodate.com/contents/ichthyosis-vulgaris

  Ichthyosis vulgaris (IV; MIM #146700) is the most common of the ichthyoses, a heterogeneous group of inherited disorders of keratinization characterized by generalized scaling of the skin of varying severity. IV is generally considered mildest in comparison with other ichthyosis types. IV is caused by pathogenic variants in the filaggrin gene (FLG), encoding profilaggrin, which is a major component of the keratohyalin granules in the granular layer of the epidermis. […] This topic will review the pathogenesis, clinical features, diagnosis, and management of IV. […] DIAGNOSIS: Clinical, Biopsy, Genetic testing.

• #2 Epidermolytic ichthyosis

  https://dermnetnz.org/topics/epidermolytic-ichthyosis

  Epidermolytic ichthyosis is one of the five main types of ichthyosis along with lamellar ichthyosis, ichthyosis vulgaris, congenital ichthyosiform erythroderma, and X-linked ichthyosis. […] Epidermolytic ichthyosis is caused by missense mutations (where a single nucleotide is changed) in the keratin genes keratin 1 (KRT1) and keratin 10 (KRT10). […] Given the similarities between various ichthyoses, a diagnosis of epidermolytic ichthyosis can be made using clinical, histopathological, and laboratory findings. The diagnosis can be confirmed with genetic testing. […] The prognosis of epidermolytic ichthyosis is variable and depends on the severity of the symptoms. There is an immediate risk of dehydration, infection, sepsis, and premature death. Patients who survive experience infection, skin fragility, and blistering episodes throughout their lives, in addition to stress and social isolation accompanying these symptoms.

• #2

  https://link.springer.com/article/10.1007/s40257-017-0313-x

  Routine skin histology is seldom of foremost value in the diagnosis of ichthyosis, except in ichthyosis vulgaris where an absence of the granular layer is suggestive, and in some forms of keratinopathic ichthyosis where epidermolysis occurs in the upper epidermis. […] For more than 30 years the gold standard for genetic analysis was the dideoxy sequencing (Sanger sequencing method; first generation) by which the coding part of the suspected disease-causing gene was analyzed, exon by exon. This was an expensive and time-consuming approach compared with the now available next generation (NGS) techniques. […] There are ichthyosis phenotypes with obvious clinical diagnosis in which the clinician can clearly assign a particular gene. But the remaining patients, especially those with mutations in ARCI genes, cannot be clearly distinguished from each other, even by very experienced clinicians. Therefore, the NGS methods such as multi-gene-panel sequencing that include all suspected candidate genes within one analysis are a perfect diagnostic approach.

• #2 Current Research Reveals New Treatment Options for Ichthyosis

  https://www.dermatologytimes.com/view/current-research-reveals-new-treatment-options-for-ichthyosis

  Genetic testing is a very important aspect in the diagnostic work-up of ichthyosis to better understand the pathophysiology of the disease and help clinicians arrive at the accurate diagnosis and appropriate management of patients skin disorders. […] An accurate molecular diagnosis is crucial for predicting prognosis and providing appropriate genetic counseling. […] According to Goldust, clinics and medical centers that provide genetic testing using whole-exome sequencing technology, which can investigate the many different genes responsible for ichthyosis, are paramount and requisite for complete patient care.

• #2 Ichthyosis Vulgaris: Causes, Symptoms, Treatment & Recovery

  https://my.clevelandclinic.org/health/diseases/21069-ichthyosis-vulgaris

  Ichthyosis vulgaris can be difficult to diagnose. Many people with mild cases often assume they just have dry skin. If moisturizers dont help, you may have ichthyosis vulgaris. […] A healthcare provider like a dermatologist can diagnose the condition by discussing your symptoms. Theyll examine your skin and ask what makes the symptoms better or worse. Theyll also ask about your familys history of skin conditions and any medications youre taking. […] Ichthyosis vulgaris is usually a clinical diagnosis that doesnt require testing. But a healthcare provider may order a skin biopsy to look at a skin sample under a microscope. Or they may order a blood test or saliva test to look for a filaggrin mutation.

• #2 Ichthyosis: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1198130-overview

  Lamellar ichthyosis is a rare, autosomal recessive, genetically heterogeneous skin disease caused by mutations involving multiple genetic loci. […] In X-linked ichthyosis, generalized scaling is present at or shortly after birth. […] Irregular stromal corneal opacities that are located anterior to the Descemet membrane are found in 16-50% of male patients, and this finding may be used to distinguish this form of ichthyosis from all other forms. […] Approximately 25% of female carriers have minor corneal opacities. […] An example of findings in X-linked ichthyosis is shown in the image below. […] Previous studies have shown a deficiency of steroid sulfatase (STS) in skin fibroblasts and a marked elevation of plasma cholesterol sulfate in patients with X-linked ichthyosis. […] Acquired ichthyosis usually occurs in adults and manifests as small, white, fishlike scales that frequently are concentrated on the extremities but may be seen in a generalized distribution.

• #2 Orphanet: Lamellar ichthyosis

  https://www.orpha.net/en/disease/detail/313

  A rare autosomal recessive congenital ichthyosis characterized by the presence of large scales all over the body without significant erythroderma. […] The diagnosis is based on the clinical appearance of the skin and can be confirmed by genetic testing. […] Histological features include orthohyperkeratosis, a normal to slightly widened stratum granulosum, acanthosis, and papillomatosis of the epidermis. […] Immunohistochemistry using antibodies directed against transglutaminase 1 or transglutaminase 1 enzyme activity measurement is available in some centers. […] Molecular testing (such as gene panel diagnosis) is possible in national reference laboratories. […] Prenatal diagnosis is based on DNA analysis of amniocentesis and chorion villus sampling materials. […] Genetic counseling should be offered to the affected families.

• #2 Prenatal diagnosis of harlequin ichthyosis. Case report

  http://www.scielo.org.pe/scielo.php?script=sci_arttext&pid=S2304-51322023000300013&lng=en&nrm=iso&tlng=en

  Ultrasonography and genetic analysis are useful tools for prenatal diagnosis. […] Diagnosis is based on identifying ABCA12 mutations. […] The diagnosis can be confirmed by chorionic villus sampling or amniotic fluid sampling. […] Prenatal genetic diagnosis should be advised for couples with previously affected children. Characteristic features on prenatal ultrasound tend to appear late, so evaluations should be repeated in the third trimester, even when the second trimester anatomic examination is normal.

• #2 Ichthyosis: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1198130-overview

  This form of ichthyosis may be associated with internal neoplasia (eg, Hodgkin lymphoma, leukemia), systemic illness (eg, sarcoidosis, HIV infection, hypothyroidism, chronic hepatitis, malabsorption), bone marrow transplantation, or the intake of certain medications that interfere with sterol synthesis in epidermal cells (eg, nicotinic acid). […] Newborns with type 2 Gaucher disease (glucosyl cerebroside lipidosis) may present with ichthyotic skin at birth prior to neurologic manifestations, which could be mistaken for a congenital form of ichthyosis.

• #2 Ichthyosis

  https://www.pcds.org.uk/clinical-guidance/ichthyosis

  The majority of patients will have an inherited ichthyosis, and depending on the type genetic testing may be needed. […] Patients with acquired ichthyosis require thorough investigation to look for an underlying cause, which includes: […] A more sudden onset of acquired ichthyosis similar to the pattern of ichthyosis vulgaris in adult life or with a generalized eczema craquel appearance suggests the possibility of internal malignancy, particularly if it occurs in a younger age group. […] The strongest association is with Hodgkin disease (accounting for over 70% of cases) and other lymphoreticular tumours, including T-cell lymphomas, leukaemias, myelodysplastic syndrome, multiple myeloma and polycythaemia vera. […] Cases linked with solid tumours are also well documented, including cancers of the ovary, kidney, liver and breast, as well as leiomyosarcoma.

• #2 Prenatal diagnosis of a rare variant of harlequin ichthyosis with literature review | BMC Medical Imaging | Full Text

  https://bmcmedimaging.biomedcentral.com/articles/10.1186/s12880-021-00586-4

  Harlequin ichthyosis (HI) is a rare and severe genetic skin disorder that occurs within the developing foetus. Due to the extremely poor prognosis, prenatal diagnosis becomes very important, especially for foetuses with no family history. […] Prenatal diagnosis mainly relies on ultrasonic, amniotic fluid and umbilical cord blood molecular detection. […] We report the prenatal diagnosis of a harlequin foetus based only on ultrasound in two cases without a family history. The diagnostic value of prenatal ultrasound in congenital harlequin ichthyosis was also summarized. […] HI can be easily detected by 2D ultrasound combined with 3D, but attention should be paid to a systematic examination in the third trimester of pregnancy according to the clinical characteristics of the disease. […] The risk of pregnancy recurrence is 25%, so prenatal diagnosis is important.

• #2 Management of Ichthyosis: A Brief Review

  https://www.skintherapyletter.com/ichthyoses/management-ichthyosis-review/

  The majority of ichthyosis therapies aim to improve the barrier function of the skin. […] Patients diagnosed with ichthyosis should be aware of the lifelong course of this group of disorders, as there is currently no cure. […] Gene therapy is not yet a reality in ichthyosis therapy; however, genetic counseling remains an integral aspect of disease management. […] The ichthyoses are typically inherited conditions exhibiting disordered keratinization secondary to excessive transepidermal water loss, with the most common variants being ichthyosis vulgaris and X-linked recessive ichthyosis. […] Ichthyosis management requires a multimodal approach, including topical and oral agents in addition to lifestyle modifications.

• #2 Comprehensive Molecular Analysis of Disease-Related Genes as First-Tier Test for Early Diagnosis, Classification, and Management of Patients Affected by Nonsyndromic Ichthyosis

  https://www.mdpi.com/2227-9059/12/5/1112

  Comprehensive Molecular Analysis of Disease-Related Genes as First-Tier Test for Early Diagnosis, Classification, and Management of Patients Affected by Nonsyndromic Ichthyosis […] Inherited ichthyoses are a group of clinically and genetically heterogeneous rare disorders of skin keratinization with overlapping phenotypes. The clinical picture and family history are crucial to formulating the diagnostic hypothesis, but only the identification of the genetic defect allows the correct classification. […] However, clinical and genetic classification of ichthyosis is important to identify possible associated diseases in syndromic forms, for genetic counseling and prenatal diagnosis, to follow the clinical course of the disease, and to start potential therapies. […] Clinical evaluation, histological and electron microscopy analysis, as well as family history are important clues for the classification of an ichthyosis form, but the correct and definitive diagnosis can be obtained when DNA analysis identifies the molecular cause of the disease. Due to the wide genetic heterogeneity, molecular analysis of multiple genes by next-generation sequencing (NGS) technology represents the most sensitive methodology to obtain the diagnosis in the greatest number of affected patients. […] In the attempt to identify the genetic cause of the disease in 17 unrelated Italian patients referred with nonsyndromic congenital ichthyosis, without having any further details regarding family history or phenotypic features, we performed an NGS analysis focused on a panel of over 50 genes that covers most forms of isolate and syndromic ichthyosis, including XLI and IV. […] In our cohort of 17 unrelated probands with congenital ichthyosis, multigene NGS analysis allowed the molecular classification of all the referred cases. The high success rate of our methodology was mostly due to a data analysis strategy that, in addition to known and new disease-causing SNVs, was able to reveal heterozygous and hemizygous large deletions, therefore confirming elevated sensitivity also for the detection of these types of CNV. […] Multigene NGS analysis is the method of choice for the comprehensive molecular testing and early classification of patients affected by any type of ichthyosis, including XLI and IV. Indeed, we herein demonstrate that targeted quantitative analysis of NGS data of a specific gene, by identifying heterozygous and homo/hemizygous CNVs, partly resolves missing heritability problem, therefore improving diagnostic sensitivity of the whole procedure, with useful implications for clinical practice.

• #2

  https://link.springer.com/article/10.1007/s40257-017-0313-x

  Hereditary ichthyoses are due to mutations on one or both alleles of more than 30 different genes, mainly expressed in the upper epidermis. […] A correct diagnosis of ichthyosis essential not only for genetic counseling but also for adequate patient information about prognosis and therapeutic options is becoming increasingly feasible thanks to recent progress in genetic knowledge and DNA sequencing methods. […] Given the conspicuous signs of widespread hyperkeratosis, scaling, xerosis, erythema, and occasional skin erosions, one may think that it is always easy to make a clinical diagnosis of ichthyosis and that patients seeking a doctor are likely to receive correct information about the disease and its treatment. In reality, however, the severe forms of ARCI and keratinopathic ichthyosis may easily be misdiagnosed as syndromic ichthyosis or epidermolysis bullosa (in neonates), and the milder forms as ichthyosis vulgaris (in older children and adults) or X-linked ichthyosis (in males), and vice versa.

Zobacz więcej