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Ichthyosis Workup

  • Author: Andrew A Dahl, MD, FACS; Chief Editor: Hampton Roy, Sr, MD  more...
Updated: Jul 07, 2016

Laboratory Studies

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
  • KID syndrome - Skin biopsy and molecular genetic analysis for mutations in the GJB2 gene, coding for connexin 26, a component of gap junctions in epithelial cells
  • Neutral lipid storage disease - Blood smear for vacuoles and skin biopsy
  • Refsum disease - Plasma phytanic levels
  • Netherton syndrome - Hair shaft examination
  • Sjögren-Larsson syndrome - Fatty alcohol: NAD oxidoreductase assay

Acquired ichthyosis may be a marker of various autoimmune disorders or malignancy. Acquired ichthyosis may also be a marker of concomitant infection with HIV in intravenous drug users and occurs after profound helper T-cell depletion. Important laboratory tests to consider in addition to HIV testing are as follows:

  • CBC count with differential and bone marrow aspirate (ie, leukemia, myelodysplastic syndromes)
  • Thyroid function tests (ie, hypothyroidism)
  • Serum angiotensin converting enzyme and lysozyme (ie, sarcoidosis)
  • Chest radiography (ie, sarcoidosis, lymphoma, HIV, tuberculosis)
  • Serum antinuclear antibody (ANA), anti-double stranded DNA (dsDNA) antibody, anticentromere antibody (ACA), and anti-Scl-70 antibody (ie, systemic lupus erythematosus [SLE], systemic sclerosis)

Imaging Studies

In congenital ichthyosis syndromes, excessive intra-amniotic debris and polyhydramnios on ultrasonography scanning in utero may be the first indication of disease.

Using ultrasonography scanning in utero, fetal foot length may be an important and probably the first marker, seen in the second trimester, for the diagnosis of harlequin ichthyosis.

Other echographic findings may include a persistently open mouth, dense amniotic fluid, and fixed flexion of the extremities.


Other Tests

Studies have shown that a low maternal serum unconjugated estriol during pregnancy screening may be a good indication of placental STS deficiency and X-linked recessive ichthyosis.

Microdeletion of the STS gene can be confirmed by fluorescence in situ hybridization (FISH) analysis of cultured amniotic fluid in X-linked ichthyosis.

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).[6]


Histologic Findings

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. In contrast to ichthyosis vulgaris, the granular cell layer may be normal. However, in some cases, it may be absent, which makes histologic differentiation from ichthyosis vulgaris very difficult.

Lamellar ichthyosis displays massive, compact orthohyperkeratosis with variable degrees of parakeratosis and a markedly thick stratum corneum. The granular layer is either normal or increased.

In epidermolytic hyperkeratosis, the skin biopsy specimen shows epidermal acanthosis and hyperkeratosis. Bullous formation may be manifested by intercellular and intracellular spaces as a result of suprabasal cytolysis within the granular layer.

The skin biopsy specimen from patients with congenital ichthyosiform erythroderma (CIE) shows compact hyperkeratosis and moderate increase in stratum corneum thickness. There is variable mild parakeratosis and acanthosis and a normal or prominent granular layer. A mild upper dermal lymphocytic infiltrate and prominent dermal blood vessels may be present.

Contributor Information and Disclosures

Andrew A Dahl, MD, FACS Assistant Professor of Surgery (Ophthalmology), New York College of Medicine (NYCOM); Director of Residency Ophthalmology Training, The Institute for Family Health and Mid-Hudson Family Practice Residency Program; Staff Ophthalmologist, Telluride Medical Center

Andrew A Dahl, MD, FACS is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, American Intraocular Lens Society, American Medical Association, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Medical Society of the State of New York, New York State Ophthalmological Society, Outpatient Ophthalmic Surgery Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Steven R Feldman, MD, PhD Professor, Departments of Dermatology, Pathology and Public Health Sciences, and Molecular Medicine and Translational Science, Wake Forest Baptist Health; Director, Center for Dermatology Research, Director of Industry Relations, Department of Dermatology, Wake Forest University School of Medicine

Steven R Feldman, MD, PhD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, North Carolina Medical Society, Society for Investigative Dermatology

Disclosure: Received honoraria from Amgen for consulting; Received honoraria from Abbvie for consulting; Received honoraria from Galderma for speaking and teaching; Received consulting fee from Lilly for consulting; Received ownership interest from for management position; Received ownership interest from Causa Reseasrch for management position; Received grant/research funds from Janssen for consulting; Received honoraria from Pfizer for speaking and teaching; Received consulting fee from No.

Chief Editor

Hampton Roy, Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Additional Contributors

Kenneth M Goins, MD Professor of Clinical Ophthalmology, Director of Cornea and External Diseases and Refractive Surgery, Department of Ophthalmology, University of Iowa Hospitals and Clinics; Medical Director of Iowa Lions Eye Bank

Kenneth M Goins, MD is a member of the following medical societies: American Society of Cataract and Refractive Surgery, Eye Bank Association of America, International Society of Refractive Surgery, Iowa Medical Society, American Academy of Ophthalmology, American Medical Association

Disclosure: Nothing to disclose.

Seth Adam Anderson Des Moines University College of Osteopathic Medicine

Disclosure: Nothing to disclose.

Matthew Rauen, MD Fellow in Corneal, External Diseases and Refractive Surgery, Department of Ophthalmology and Visual Sciences, University of Iowa Health Care

Matthew Rauen, MD is a member of the following medical societies: American Academy of Ophthalmology

Disclosure: Nothing to disclose.

Arash Taheri, MD Research Fellow, Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine

Disclosure: Nothing to disclose.

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This direct illumination slit lamp photograph discloses a reticular central corneal haze that is seen bilaterally. Visual acuity is 20/20 in both eyes. The patient's chief complaint is photophobia and dry scaly skin.
This slit beam illumination photograph of the cornea localizes the corneal opacity to the posterior stroma and the pre-Descemet membrane region. This type of corneal opacity is commonly present in X-linked recessive ichthyosis.
An orbital mass is shown on CT scan in a 38-year-old male with human immunodeficiency virus (HIV) who presented with a late onset generalized ichthyotic rash and proptosis.
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