Harlequin ichthyosis: the rare fish skin disease

Ariadna López's skin has been cracked since she was born.

From head to toe, dry and cracked, sometimes red.

The 21-year-old suffers from harlequin ichthyosis, a very strange dermatological ailment caused by a genetic mutation that alters the process of formation of the epidermis.

It is, as the etymology of her name says, a kind of fish skin, always scaly.

Every day is an essential hygiene ritual for Ariadna: she hydrates herself with creams every few hours, showers two or three times if necessary, bathes with a coal tar preparation several times a week and exfoliates her body with a glove special to remove dead skin.

Always.

You cannot miss or delay care.

It depends on this that the disease is not complicated by infections or other more serious alterations.

“I was born with this, so for as long as I can remember, I've accepted it.

It affects me on a day-to-day basis because of the time and money that care requires.

But there are a series of things that I have to do, yes or yes”, settles the young woman.

Ariadna López, 21, suffers from harlequin ichthyosis, a very rare dermatological ailment that causes flaking of the skin.GALA ESPÍN

Harlequin ichthyosis is a very rare ailment.

There are hardly a couple of cases in Spain, according to the information available to the Spanish Ichthyosis Association: Ariadna and another smaller girl, say the voices consulted.

Many of the babies born with this disease die shortly after due to the associated complications, as they have problems breathing, eating and even infections from the wounds caused by the skin alteration.

Affected newborns enter the world with a kind of armor made up of thick plates of scales separated by deep fissures—hence the harlequin surname.

The fissures facilitate infections through the skin and this armor can make it difficult to hydrate and regulate body temperature.

A review of 45 cases published in 2011 revealed that 25 survived (between the ages of 10 months and 25 years) and another 20, all under the first three months of life, died of respiratory failure or sepsis, which is a uncontrolled response of the immune system to an infection.

The disease is so rare that there are no clear prevalence data.

Only calculations and approximations: less than one case per million individuals, according to the Orphanet database.

In a 2014 study, the authors then recalled that there were some 200 cases reported internationally at the time.

The first described was in 1750 by Reverend Oliver Hurt in the city of Charleston, South Carolina (United States): “The skin was dry and hard, and seemed to be cracked in many places, somewhat like the scales of a fish.

The mouth was large and round, and wide open, ”he recounted in his diary.

The scientific community has described more than 30 types of ichthyosis, all with different degrees of incidence and severity in the population: some affect only the skin (non-syndromic, such as harlequin ichthyosis) and in others, the genetic defect manifests itself in other organs other than the skin (syndromic).

The harlequin type is included within a subgroup of non-syndromic, which are autosomal recessive congenital ichthyosis: they are transmitted from parents to children as long as both parents are carriers of the genetic mutation.

In the case of harlequin ichthyosis, there is a 25% chance in each pregnancy that the child will have the disease.

Ariadna's mother, Mari Carmen, helps her daughter with the constant hygiene and hydration that the young woman's skin needs.

ESPIN GALA

A Spanish study published in the

assessed a prevalence of all autosomal recessive congenital ichthyosis of between 7 and 16 cases per million inhabitants.

But in harlequin ichthyosis, which is the most serious of them, it is much less, explains Ángela Hernández, member of the Spanish Academy of Dermatology and Venereology and author of the research.

“It's extraordinarily rare and sometimes they don't survive.

I have 80 patients with ichthyosis and only two of them have harlequin ichthyosis.

And these two cases have survived because they were born at a time when intensive care units were already very good, ”she values.

The cause of this condition is the alteration of the ABCA12 gene, which alters keratinization, the process by which the epidermis is formed.

“The ABCA12 gene is involved in a lipid transporter in the cells that make up the epidermis.

As this does not work well, patients have a totally altered epidermis, which does not serve as a defense against the external environment and is unable to hold water, for example”, explains the dermatologist, who works at the Niño Jesús Hospital in Madrid.

This genetic alteration prevents the formation of the skin barrier that regulates temperature and protects against infections and dehydration.

Alopecia and joint problems

It is not easy to deal with harlequin ichthyosis.

This flaking of the skin leads to other bodily alterations that complicate the prognosis from birth, Hernández points out: “They suffer from ectropion [the eyelid folds out], which causes the eyelids not to close properly.

They also tend to have their ears stuck together, lose flexibility in their fingers and suffer from complete alopecia.

There is a deterioration in their physical appearance, but they also have eye and joint problems and do not sweat well”.

Ariadna has been through —and is going through— all of that.

The young woman, who is studying a cycle of social integration, visits dermatologists, otolaryngologists, rheumatologists and ophthalmologists.

"I don't have a well-formed eyelid and it doesn't close completely, so I have to moisturize my eye because it dries out a lot, wipe my eyelid with a washcloth so that the scaly skin doesn't get inside, and put an ointment on the edge of my eye before sleep.

I also suffer from burning and itching of the skin and I have problems with my joints because, as the skin was not very elastic, the bones could not grow well and I have arthritis.

In winter, the skin dries out more and it is more difficult for me to walk or pick up something, ”she relates.

Ariadna suffers from alopecia due to harlequin ichthyosis and has been wearing a wig since she was 11 years old.Gala Espín

The scaling can affect the cornea and also the ear, plugging it with dry skin.

These patients also suffer from hyperkeratosis, a thickening of the skin that can encapsulate or compress the extremities and affect motor skills.

As they do not sweat properly, they do not tolerate hot environments well, "such as fever, summer or intense physical exercise," says Hernández.

For Ariadne, for example, fever is martyrdom.

“I can't expel the heat by sweating and the fever usually lasts a long time.

My skin becomes super rigid and I can hardly move, "says the young woman.

The disease, visible to the naked eye, also carries a strong stigma that weighs heavily, especially on the street: “When I was little I didn't go out much because my skin was very bad and needed a lot of care.

Then, the few times I went out, when I went to the park, the children wanted to play with me and hold my hand, but their parents wouldn't let them because they thought it was contagious.

Others did not shake my hand because it disgusted them, ”he says now, hardly flinching.

Adolescence, admits Ariadna, was even harder: “It was very complicated.

I suffered from depression and anxiety because I did not accept having bad skin.

It bothered me, for example, to interrupt a meeting to go and apply cream.

At school there was no problem, the worst was on the street: unknown people, they would stare and say 'Ala, you've burned yourself' or they would tell my mother why she didn't take good care of me, that they were very poorly cared for” .

The comments, the prying eyes and the impertinent questions hurt.

Ariadna collects the remains of her skin after an hour of peeling.

Espin Gala

Ariadna, who suffers from alopecia, has been wearing a wig since she was 11 years old.

Although now she is beginning to go out with a handkerchief, "little by little overcoming complexes", she says: "Now I am in the process of accepting and if one day my skin is very bad, it does not affect me so much, I think that it will pass”.

There is "a cruel point" that accompanies this disease, agrees Hernández.

“The skin looks great, it is your cover letter.

And in this disease, the physical appearance is very limiting and makes them suffer a lot.

There is a significant deterioration in mental health.

José María Soria, president of the Spanish Association of Ichthyosis, assures that a diagnosis of this disease is "a hard blow" for the patient and his family.

“The ones who begin to suffer from the disease are the parents, who find themselves with a disease that they do not know about and do not know if they will survive.”

Added to this, over time, is the psychological weight of the looks of others, but Soria is blunt: “You don't have to hide anything.

You have to show it to normalize it.”

Research

Beyond that "physical and psychological burden" that patients and their families carry, as Soria recalls, those affected also add the economic weight of the disease.

“Any ichthyosis requires a series of topical skin products that are not financed by the National Health System.

You have to pay for them yourself”, protests the president of the patients' association.

For this reason, for all this, Ariadna wants to make her illness visible: “So that everyone is aware of the amount of expenses and hours of life that those affected lose by applying treatments that the National Health System does not cover at all and that are only palliative because we suffer from a lot of itching and stinging, among many other things”.

Make visible to also stop stigmatizing, she emphasizes: “Now that I'm older I get along much better.

Still, it hasn't been easy having to put up with looks of disgust or pity every day, comments out of place, gestures of contempt... And all this is due to ignorance and lack of knowledge.

We want people to put themselves in our shoes to fight for ichthyosis research, so that one day we can talk about it in the past tense”.

As in all rare diseases, in addition, research in search of a cure or therapeutic alternatives to overcome the risks of the disease, goes from being a challenge to an odyssey.

It is not easy to start a study, although Dr. Hernández admits that, in recent years, the accelerator has been stepped on and they have begun to test biological drugs to improve the situation of patients.

“In keratinization disorders, we know that patients have systemic inflammation.

What we try to do is reduce external inflammation and improve the condition of the skin.

The ideal would be to find a biomarker that allows us to carry out targeted treatment with a biological drug.

But, of course, for this type of research we need money and the economic resources that are dedicated to rare diseases is,

The interest of the pharmaceutical industry, with so few patients, is very limited.

"They are unprofitable," laments the dermatologist.

Ariadna's skin is scaly and cracked due to harlequin ichthyosis.GALA ESPÍN

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