About ichthyosiform erythroderma with leukocyte vacuolation

What is ichthyosiform erythroderma with leukocyte vacuolation?

Chanarin Dorfman syndrome is a rare hereditary disorder of fat (lipid) metabolism. It is characterized by scaly skin (ichthyosis), degeneration of the muscles (myopathy), and abnormal white blood cells with small spaces (vacuoles) filled with fat (lipids).



What are the symptoms for ichthyosiform erythroderma with leukocyte vacuolation?

Chanarin-Dorfman syndrome can affect many systems. All patients have skin findings that are usually present at birth: redness, fine scaling, dark pigmentation and severe Itching which leads to scratching and skin-picking (excoriation). The skin appearance is referred to “ichthyosiform nonbullous erythroderma”. Patients also have liver disease with lipid storage which can lead to liver failure. About 60% of patients also have muscle problems. They have slowly progressive Weakness of the proximal arms and legs. When the muscles are affected they release their enzymes in the blood, which can be detected by the presence of a CK elevation. Exercise intolerance has never been reported, but many patients reported early fatigability.

Less commonly, other systems can be involved. Around 40% of patients have eye problems consisting mainly in cataracts or eyelids pointing outwards (ectropion). Approximately 25% of patients have progressive hearing loss. Around 25% have cognitive impairment. Short stature and growth retardation have also been reported. Some patients have intestinal problems such as fatty Diarrhea (steatorrhea) and enlarged spleen. Some have orthopedic problems and kidney dysfunction.



What are the causes for ichthyosiform erythroderma with leukocyte vacuolation?

Chanarin-Dorfman syndrome is caused by changes (mutations) in the ABHD5 gene located on chromosome 3. This gene produces a protein involved in fat metabolism called CGI-58. This protein is called a co-factor because it helps the activity of the main enzyme, which is adipose triacylglycerol lipase (ATGL). The function of this enzyme is to break down a type of fat called triacylglycerol (TAG). This process is disturbed when either the enzyme or the helper protein doesn’t work properly. When the fat (triacylglycerol) cannot be broken down, it accumulates in various parts of the body as lipid droplets and causes different symptoms. This is what happens in a group of disorders called ‘neutral lipid storage disease’. It comprises two entities:

When the mutation occurs in the gene for the main enzyme (ATGL), the disease is called ‘neutral lipid storage disease with myopathy’.

When the mutation occurs in the gene for the helper protein (CGI-58), the disease is called ‘neutral lipid storage disease with itchthyosis’, or Chanarin-Dorfman syndrome.

It is important to distinguish between the two because the clinical presentations are very different. In the first one, patients usually present in early adulthood with muscle abnormalities caused by the accumulation of fat. In Chanarin-Dorfman syndrome, patients primarily have skin abnormalities that are apparent at birth. For this reason, Chanarin-Dorfman syndrome is also part of a group of diseases called ‘itchthyoses’, which are characterized by skin abnormalities. Another difference is the absence of heart problems (cardiomyopathy) in Chanarin-Dorfman syndrome, whereas they are present in first one.

The genetic mutation in Chanarin-Dorfman syndrome leads to abnormal accumulation of fat (lipid droplets) in many cells, especially in the skin, liver and white blood cells. The effect on the skin is an abnormal permeability, which leads to a characteristic rash and intense itching. In the liver, the lipid droplet accumulation leads to fatty change called “steatosis” that can eventually progress to cirrhosis and liver failure.

Chanarin-Dorfman syndrome is inherited in an autosomal recessive pattern, which means the individual inherits an abnormal gene from each parent. If an individual receives one normal gene and one abnormal gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the abnormal gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.



What are the treatments for ichthyosiform erythroderma with leukocyte vacuolation?

There is no effective treatment for Chanarin-Dorfman syndrome. However, it is recommended to have a low fat diet (specifically low long-chain fatty acid and minimal saturated fat), enriched with medium-chain triglycerides, ursodiol (a bile acid) and vitamin E. This would decrease the liver size and normalize the liver enzymes. This diet has no effect on skin symptoms. To alleviate itching and other skin symptoms, it is recommended to apply moisturizers on the skin. Vitamin A derivatives like acitretin are useful for skin and muscle manifestations, but are often considered contraindicated if the liver enzymes are impaired, which is commonly the case. However, improvement in skin symptoms without deleterious effect on liver function has been reported with the use of acitretin. There is no consensus about the use of retinoid in Chanarin-Dorfman syndrome with abnormal liver function. One case of liver transplant followed by the usual dietary modifications has been reported with stabilisation of the skin and intellectual disability deterioration after 1 year, but there are insufficient studies to conclude the effectiveness and the long-term effects of liver transplantation.



What are the risk factors for ichthyosiform erythroderma with leukocyte vacuolation?

A hereditary skin condition known as epidermolysis ichthyosis (EI) is distinguished by different degrees of blistering and subsequent reactive scaling of the skin. Mid-epidermal splitting and hyperkeratosis, often known as epidermolytic hyperkeratosis, are present in the underlying histology (EHK). The symptoms might range from minor burning upon friction to severe erosions or widespread warty scaling, depending on the kind of underlying mutation.

  • Missense mutations in the keratin 1 (KRT1) and keratin 10 genes, which result in a single nucleotide alteration, cause epidermolytic ichthyosis (KRT10)
  • Severe palmoplantar keratoderma is linked to KRT1 mutations. KRT10 mutations typically don't cause palmoplantar symptoms. Mutations in the KRT9 gene cause epidermolysis of palmoplantar keratoderma, which only affects the palms and soles. The flattened squamous keratinocytes of the superficial epidermis contain keratin tonofilaments, which are composed of keratin 1 (K1) and 10 (K10). They constitute a strong structural element of the epidermis.
  • Genetically, EI is an autosomal dominant condition. When a single copy of a defective gene is required to induce a specific disease, dominant genetic diseases result. The faulty gene may be brought on by a new mutation (gene alteration) in the sick person or it may be inherited from either parent. For each pregnancy, there is a 50% chance that the faulty gene will be passed from the affected parent to the fetus. Both men and women are at the same level of danger. Some EI instances result from unintentional mutation.


Symptoms
Hearing impairment,Sweating
Conditions
Red scaly skin,Turned-out eyelid
Drugs
Acitretin,Soriatane



Is there a cure/medications for ichthyosiform erythroderma with leukocyte vacuolation?

The condition of epidermolysis ichthyosis (EI) cannot be cured. Therapy's main objective is to lessen hyperkeratosis. Topical keratolytic such as lactic acid, alpha-hydroxy acid, or urea can accomplish this. Additionally, topical emollients with glycerin are frequently helpful. Significant improvement can be achieved with topical and oral retinoids, although caution must be exercised to prevent a rise in skin fragility.

  • To adequately inform and counsel parents about epidermolysis ichthyosis (EI), an accurate diagnosis is crucial.
  • Prenatal diagnosis and genetic counseling are other options.
  • Infection, secondary sepsis, and electrolyte imbalance are all heightened risks for newborns with epidermolytic ichthyosis who have denuded skin.
  • The neonatal ICU should receive these infants so that it can monitor them and provide any necessary care.
  • To prevent further injury to the skin, they should be handled gently.
  • In the newborn phase, moisturization/emollients and wound care for blistering are crucial.
  • Topical emollients and topical keratolytic are typically the cornerstones of treatment for older kids.
  • Scale buildup encourages the growth of bacteria, especially Staphylococcus aureus, which is frequently linked to odor.
  • The use of diluted bleach baths or mild antibacterial soaps may be helpful to patients.
  • Treatment with oral or topically applied retinoids may also be beneficial for some people.
  • When receiving systemic treatments for epidermolysis ichthyosis, schedule routine follow-up appointments as necessary for symptomatic alleviation or to monitor laboratory tests.


Symptoms
Hearing impairment,Sweating
Conditions
Red scaly skin,Turned-out eyelid
Drugs
Acitretin,Soriatane



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