Netherton's syndrome: what is it, symptoms, treatment, prognosis

What is Netherton Syndrome?

Netherton's syndrome Is a rare hereditary disease characterized by skin flaking, hair abnormalities, increased susceptibility to atopic eczema (a skin condition that can lead to dry, red, and flaky skin), elevated IgE levels, and other related symptoms. Netherton's syndrome is inherited as an autosomal recessive trait.

Signs and symptoms

Newborns with Netherton syndrome have reddened skin (erythroderma) and sometimes a thick, parchment-like covering of the skin (collodion membrane). The skin is red and scaly all over. Hair is brittle and breaks easily due to trichorexis or "bamboo hair", resulting in short, sparse hair. In older children and adults, the scales may have a distinct circular pattern. Another sign of Netherton syndrome is a predisposition to allergies, asthma and eczema.

Babies with Netherton syndrome can be born prematurely. Problems with weight gain in infancy and childhood are common and can be serious. Children may also have recurrent skin infections and 

sepsis. Patients may develop hypernatremia (elevated blood sodium levels) due to excessive fluid loss from the skin. Since hair cannot be touched at birth, and in the first months of life it can be sparse in everyone in infants, the characteristic hair defect that characterizes Netherton syndrome may not initially show up.

Babies with Netherton syndrome may be misdiagnosed with congenital ichthyosiform erythroderma, atopic dermatitis or psoriasis.

Causes

Netherton's syndrome is caused by mutations in a gene SPINK5. This gene contains instructions for making a protein called LEKT1. LEKT1 is a type of serine peptidase inhibitor. Serine peptidase inhibitors control the activity of enzymes called serine peptidases, which break down other proteins. LEKT1 is present in the skin and in the thymus, which is located behind the breastbone and plays an important role in the immune system by producing white blood cells called lymphocytes. LEKT1 controls the activity of some serine peptidases in the outer layer of the skin (epidermis), especially the stiffness outer surface known as the stratum corneum, which provides a strong barrier between the body and the surrounding environment. Serine peptidase enzymes are involved in normal skin shedding by helping to break down the bonds between stratum corneum cells. LEKT1 is also involved in normal hair growth, lymphocyte development in the thymus, and control of peptidases that trigger immune system function.

Gene mutations SPINK5 lead to the fact that the LEKT1 protein is unable to control the activity of serine peptidase. The lack of LEKT1 function allows serine peptidases to be abnormally active and to break down too many proteins in the stratum corneum. As a result, too much skin loss occurs, and the stratum corneum becomes too thin and easily destroyed, leading to skin abnormalities that occur in Netherton's syndrome. Loss of LEKT1 function also leads to abnormal hair growth and immune dysfunction, leading to allergies, asthma and eczema.

Netherton's syndrome is inherited in an autosomal recessive manner.

Affected populations

Netherton's syndrome is a rare inherited disorder. Approximately 150 cases have been reported in the medical literature, but the true number of patients may be much higher due to difficulties with diagnosis and overlapping symptoms with common atopic dermatitis and other congenital ichthyosis.

Symptomatic disorders

Symptoms of the following disorders may be similar to those of Netherton's syndrome. Comparisons can be useful for differential diagnosis.

• Ichthyosis or "keratinization disorders" are general terms that describe a group of scaly skin diseases. They are characterized by an abnormal accumulation of a large number of dead skin cells in the upper layer of the skin. It is believed that the transformation of an abnormally large number of epidermal cells into squamous cells is caused by a defect in the metabolism of skin cells known as "corneocytes" or the fat-rich matrix around these cells. These cells can be thought of as bricks, and the matrix is ​​the solution holding these cells together.
• Congenital ichthyosis - hereditary skin disease. It is characterized by generalized, abnormally red, dry and rough skin with large, rough and small white scales. Usually, patients experience itching. The skin on the palms and soles of the feet can be overly thick.
• X-linked ichthyosis is a hereditary skin disorder that affects men. X-linked ichthyosis results from a deficiency of the enzyme steroid sulfatase. It is characterized by brownish scales on the back of the neck, back and legs.

Diagnostics

The disease is diagnosed based on symptoms and confirmed by genetic testing for changes in the gene SPINK5. Other tests, such as a thorough examination of the hair and a skin biopsy to obtain a small sample of skin for examination under a microscope may also be useful for staging diagnosis.

Standard treatments

Treatment for Netherton syndrome is symptomatic, often difficult, and must be tailored to the specific needs of the patient. Recommendations include the regular use of emollient and moisturizing creams and lotions. Other topical agents should be used with caution, as skin with Netherton syndrome may tolerate ingestion of ingredients of some topical preparations into the bloodstream, which may pose a danger to child.

Topical keratolytic agents such as urea or lactic acid derivatives can be limited to skin irritation and should generally be used in older children. Basic treatment also includes oral antihistamines, which can help control pruritus, the eczematous component, and topical or systemic antibiotics as needed.

Anti-dandruff shampoos and topical steroids can help treat flaky scalp. Oral and topical steroids are helpful in reducing inflammation and the eczematous component of the disease. However, the well-documented side effects of long-term steroid use must be considered. Oral retinoids have been used with varying success, resulting in dramatic improvements in some patients and severe worsening in others.

Forecast

The prognosis can be difficult in newborns with life-threatening complications and high postpartum mortality. Skin manifestations and hair abnormalities persist throughout life, but the disease tends to improve with age, and most patients begin to thrive in the second year of life.

Most people with Netherton syndrome have immune system problems such as food allergy, hay fever, asthma or inflammatory skin diseasecalled eczema.

Lilia Khabibulina/ article author