Ichthyosis Workup

Updated: May 09, 2023
  • Author: Andrew A Dahl, MD, FACS; Chief Editor: Hampton Roy, Sr, MD  more...
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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.