Lamellar Ichthyosis - Causes, Symptoms, Diagnosis, Complications, and Management.

Introduction:

Lamellar ichthyosis is an autosomal recessive disease in which a child will get affected by the disease when they receive a mutated gene, one from each parent. Genes (basic unit of heredity) are found in pairs where a gene each is inherited from the mother and the father. Lamellar ichthyosis is present at birth and continues to be there for the rest of their life. Individuals with this diseasehave a normal lifespan, but in the neonatal period, chances of death are high because of secondary infection and dehydration. Lamellar ichthyosis, caused by a mutation, has no known cure. Therefore, therapy focuses on symptom relief and improving an individual's quality of life. It requires using creams that a dermatologist prescribes to prevent the skin from hardening and keep it moisturized.

What Are the Other Names for Lamellar Ichthyosis?

• Collodion baby.

• Collodion baby syndrome.

• Congenital lamellar ichthyosis.

What Causes Lamellar Ichthyosis?

It is caused by a mutation (change) in the gene. Genes are responsible for producing proteins present in the outer layer of the skin. In the case of lamellar ichthyosis, the formation of the skin is disturbed because of gene mutation resulting in impaired skin functions like impaired body temperature, secondary infection, and less water retention. Changes in the TGM1 gene are the most common cause of lamellar ichthyosis. This gene produces certain enzymes (transglutaminase 1) and proteins. Transglutaminase 1 forms a cell envelope, a structure covering skin cells. It acts as a barrier between the body and the environment. Mutation in other genes can also cause this disorder, but the ratio is less. Researchers have recently found various chromosomal sites containing genes related to the disorder, but specific genes have not yet been identified.

What Are the Symptoms of Lamellar Ichthyosis?

Babies born with this skin disorder are called collodion babies. It is because babies with this condition are born with a clear, shiny sheath that covers their skin, called a collodion membrane.

This membrane gets peeled off in the first few weeks of life, exposing the skin underneath, which looks dark, scaly, and tight. Babies have tight skin, making their lips and eyelids turn outward. In this disorder, the outer layer of the skin (epidermis) cannot perform the protective function of a normal epidermis, resulting in various issues, including:

• Secondary infections.

• Loss of water.

• Unstable body temperature.

• Difficulty in breathing.

• Difficulty in feeding.

• Fluid and electrolyte imbalances (loss of balance in minerals present in the body).

Symptoms seen in older children and adults are:

• Skin covered with dark, large, plate-like scales on most of the body.

• Difficulty closing the eyes due to the tightness of the skin.

• Eyelids turn outward, which irritates the inner eyelid and causes dryness of the eyeball.

• Loss of hair due to thickened scales on the scalp.

• The thickness of nails increases.

• The skin on the palm and sole gets thickened.

• Decrease in sweating ability.

How to Diagnose Lamellar Ichthyosis?

Lamellar ichthyosis is diagnosed by performing the following tests:

1. Genetic Testing: It helps to find out the mutation in the gene. It is also known as DNA testing, as it identifies the changes in the structure of the DNA (carrier of genetic information responsible for growth and development).

2. Fetoscopy: Microscopic examination of amniotic fluid or fetal skin obtained by fetoscopy. Fetoscopy is done during pregnancy to evaluate and treat the fetus in the womb for congenital disorders (present at or before birth). Fetoscopy uses a fetoscope with a thin tube and a small camera at the end to see. Fetoscope is hollow, and the physician can insert surgical tools to collect amniotic fluid or fetal tissue for biopsy.

3. Biopsy: Skin biopsies to determine histological changes using an electron microscope. A biopsy is a procedure under local anesthesia where tissue is extracted to examine the cells for any abnormality in the laboratory.

4. Genetic testing for TGM1 (the gene highly responsible for the development of this disorder) gene is performed to confirm the diagnosis.

What Are Its Complications?

The following are the complications associated with lamellar ichthyosis:

• Eyelids move upward, resulting in dryness of the eyeball. Suppose left untreated leads to blindness.

• Excess formation of scales in the external ear canal leads to bacterial infections.

• Loss of collodion membrane in newborns makes them prone to numerous secondary infections.

What Are the Treatment Methods?

In lamellar ichthyosis, moisturizers play an important role in controlling the dryness in the skin during the infant period and throughout life. Moisturizers enhance the flexibility of the outer layer of the skin, hydrate and restore the protective function and help cover and remove thick scales.

For Infants: In addition to moisturization, newborns should be kept in the neonatal ICU to control body temperature and electrolyte imbalance. Newborns should be referred to ophthalmology to manage the upward lift of eyelids to prevent dryness of the eyeball.

After One Year: Microfiber washcloth or urea may be used to remove the scales mechanically. Urea is a humectant that retains moisture and acts as a keratolytic (breaks down the skin's outer layer and reduces the scales' thickness). However, salicylic acid is not advisable in infants and children due to its high absorption.

Older Children and Adults: Moisturizers and keratolytic are used in topical treatment. Salicylic acid is used in localized areas for adults.

In case of severe lamellar ichthyosis, oral retinoids are used. However, the use of oral retinoids is limited because of their effect on bones and other ligaments (a strap that connects two bones, mainly in joints).

Acitretin is a synthetic retinoid used for lamellar ichthyosis. Though its mechanism is unclear, it controls the proliferation of cells in the outer layer. Long-term use of oral retinoids affects bone mineralization (the process by which bone is formed) and causes calcium deposition in ligaments. Some other side effects of retinoids are dry mucosa, hair loss, and itching.

Conclusion:

Lamellar ichthyosis, a rare genetic skin disorder, presents at birth and continues for the rest of the life. Although distressing and disfiguring, it is not life-threatening, however, newborns may experience symptoms at birth that could endanger their lives. Moisturizers play a vital role in the treatment of this disorder throughout life. Consultation with a physician is necessary if the symptoms progress.