Butterfly Children Or Epidermolysis Bullosa (EB)

This is any of a group of inherited chronic noninflammatory skin diseases in which large blisters and erosion develop after slight trauma, Blistering often appears in infancy in response to simply being held or handled. In rarer forms of the disorder, EB can be life-threatening. There is no cure for the disorder. Treatment focuses on preventing and treating wounds and infection. Also called Cotton Wool Babies or Crystal Skin Children

It was first described in 1870 by Ferdinand Ritter von Hebra;  an Austrian physician and dermatologist known as the founder of the New Vienna School of Dermatology, an important group of physicians who established the foundations of modern dermatology.

Epidermolysis bullosa (Picture Credit; dermamin)

A very rare genetic connective tissue disorder that affects about 1 child out of every 20,000- 50,000 births worldwide
The disorder occurs in every racial and ethnic group throughout the world and affects both sexes

Signs and Symptoms

•   Fluid-filled blisters on the skin, especially on the hands and feet due to friction

•   Deformity or loss of fingernails and toenails

•   Internal blistering, including on the vocal cords, esophagus and upper airway( resulting in Hoarse cry, cough, or other breathing problems)

•   Skin thickening on the palms and the soles of the feet

•   Scalp blistering, scarring and hair loss (scarring alopecia)

•   Thin-appearing skin (atrophic scarring)

•   Tiny white skin bumps or pimples (milia)

•   Dental problems, such as tooth decay from poorly formed enamel

•   Blisters in or around the mouth and throat resulting in Difficulty swallowing (dysphagia)

•   Blisters around the eyes and nose

•   Blisters on the skin as a result of minor injury or temperature change

•   Blistering that is present at birth

Epidermolysis bullosa blisters may not appear until a toddler first begins to walk or until an older child begins new physical activities that trigger more intense friction on the feet.

Types
4 major types and 30 different subtypes have been described based on the precise ultra structural level at which the split responsible for blistering occurs.
The major types include;

•  Epidermolysis bullosa simplex (EBS) ; Epidermolytic

•  Junctional epidermolysis bullosa (JEB) ; Lucidolytic

•  Dystrophic epidermolysis bullosa (DEB) ; Dermolytic

•  Kindler syndrome; Mixed type

François Henri Hallopeau, a french dermatologist, described the Dystrophic type and seperated it from Simplex type in 1898
Junctional EB was described by Herlitz in 1935

Causes

The human skin consists of two layers: an outermost layer called the epidermis and a layer underneath called the dermis. In individuals with healthy skin, there are protein anchors between these two layers that prevent them from moving independently from one another (shearing).
In people born with EB, the two skin layers lack the protein anchors that hold them together, resulting in extremely fragile skin—even only minor mechanical friction (like rubbing or pressure) or trauma will separate the layers of the skin and form blisters and painful sores. Sufferers of EB have compared the sores with third-degree burns.
Furthermore, as a complication of the chronic skin damage, people suffering from EB have an increased risk of malignancies (cancers) of the skin.
More than 1000 mutations, encompassing more than 10 structural genes, have now been documented concerning Epidermolysis Bullosa.
    The Genetic Mutations of structural proteins of the epidermis
EBS;
Intraepidermal tonofilaments - Keratin 5, 14 (autosomal dominant disorders)
Junctional EB
Intralamina lucida - anchoring filaments and hemidesmosome, laminin 5, BP Ag 2, α6β 4 integrin (autosomal recessive disorder)
Dystrophic EB
Sublamina densa - anchoring fibrils, collagen VII ( autosomal dominant or autosomal recessive ).

Investigations/Diagnosis
Prenatal testing
Transmission electron microscopy
Immunofluorescence mapping (IFM)
Mutation analysis
Electron microscopy


Differential Diagnosis
Thermal Burns

 Complications

• Infection

• Sepsis

• Deformities; fusion of fingers or toes and abnormal bending of joints (contractures), such as those of the fingers, knees and elbows.

• Malnutrition and anemia. Blisters in the mouth can make eating difficult and lead to malnutrition. This may lead to anemia, delayed wound healing or, in children, slowed growth.

• Dehydration. Large, open blisters can cause loss of body fluid that leads to severe dehydration.

• Constipation due to painful blisters in the anal area. It can also be caused by not ingesting enough liquids or high-fiber foods, such as fruits and vegetables.

• Eye disorders. Inflammation of the eye can harm the clear covering over the eye (cornea) and, sometimes, cause blindness.

• Skin cancer; squamous cell carcinoma.

• Death. Infants with a severe form of junctional epidermolysis bullosa are at high risk of infections and loss of body fluids from widespread blistering. Their survival also may be threatened because of blistering, which may hamper their ability to eat and breathe. Many of these infants die in childhood.

Treatment
Presently, there is no cure for EB.
The treatment of epidermolysis bullosa (EB) is primarily preventive and supportive
Prevent Blisters
    Avoid getting too hot by keeping rooms at an even temperature
    Apply lotion to the skin to reduce friction and keep the skin moist
    Wear soft clothing
    Use sheepskin on car seats and other hard surfaces
    Wear mittens at bedtime to help prevent scratching.

Treating Blisters
    Reduce pain or discomfort
    Prevent loss of body fluid
    Promote healing
    Prevent infection.
    Safely break a blister in its early stages; punctured with a sterile needle or a blade. This may prevent the accumulation of fluid and pressure and may thus prevent the blister from extending. Complete and gentle drainage of the fluid, accomplished by leaving the roof of the blister intact and by covering the affected area with white petrolatum–impregnated gauze, helps to promote an environment most optimal for healing. If the blister repeatedly refills with fluid, it should be drained several times.
    Prescribing a mild painkiller so that changing bandages won’t hurt as much
    Recommending special bandages that will help the blisters to heal, lessen the pain, and prevent infection.

Treating Infection
    A soaking solution
    An antibiotic ointment; daily application of polymyxin, bacitracin, or silver sulfadiazine topical ointments to treat open or partially healed wounds,Gentamicin soaks (480 mg/L saline), acetic acid soaks (white vinegar), and the addition of small amounts of bleach to the bath water (eg, 1/8 cup per full tub) have been used to decrease the overgrowth of pseudomonas and staphylococcal organisms.
    An oral antibiotic to reduce the growth of bacteria
    A special wound covering (for sores that don’t heal).

Treating Epidermolysis bullosa (Picture Credit: nhs)

Preventing Nutritional Problems
In some people with EB, blisters may appear in the mouth and esophagus, making it hard to chew and swallow. Over time, this may lead to nutritional problems. Because nutrition is so important for proper growth and development, it is important that children with EB eat well. Here;
    Feed the baby using a bottle with a special nipple, an eyedropper, or a syringe.
    When the baby is old enough to take in food, add extra liquid to finely mashed food to make it easier to swallow.
    Give the baby soups, milk drinks, mashed potatoes, custards, and puddings.
    Never serve food that is too hot.
Dietitians can help anyone with EB by:
    Providing recipes for food that is nutritious and easy to eat
    Suggesting nutritional supplements;Vitamin and iron supplements are advised if nutritional compromise is present
    Recommending diet changes to prevent stomach or intestinal problems; a blenderized diet is recommended

Surgery
Esophageal dilatation or insertion of a gastrostomy tube may be required if esophageal strictures develop.
Patients with limited donor sites for a skin graft may need advanced therapy with bioengineered skin products eg, composite cultured skin (CCS), Graftskin, Dermagraft
Surgical intervention for contractures.


Intensive studies are underway to find better ways to treat and relieve the symptoms of epidermolysis bullosa, including:
    Gene therapy
    Bone marrow transplantation
    Protein replacement therapies
    Cell-based therapies


Prognosis
Mild forms of epidermolysis bullosa improve with age.Very serious forms of epidermolysis bullosa have a very high mortality rate.

NOTES;

1. DEBRA | what is eb

2. Dermapath | Epidermolysis Bullosa

3. Fine JD, Mellerio JE. Epidermolysis Bullosa. In: Bolognia JL, Jorizzo JL, Schaffer JV, et al, eds.Dermatology. 3rd ed. Philadelphia, Pa:Mosby Elsevier; 2012:chap 32

4. Fine JD, Eady RA, Bauer EA, et al. The classification of inherited epidermolysis bullosa (EB): Report of the Third International Consensus Meeting on Diagnosis and Classification of EB. J Am Acad Dermatol. Jun 2008;58(6):931-50

5. [Guideline] Fine JD, Eady RA, Bauer EA, et al. The classification of inherited epidermolysis bullosa (EB): Report of the Third International Consensus Meeting on Diagnosis and Classification of EB. J Am Acad Dermatol. Jun 2008;58(6):931-50

6. Mayo Clinic | epidermolysis bullosa

7. Medical Dictionary; The American Heritage® Medical Dictionary Copyright © 2007, 2004 by Houghton Mifflin Company. Published by Houghton Mifflin Company.

8. Medscape | article; 909549

9. National Institute Of Arthritis And Musculoskeletal Disease | epidermolysis bullosa

10. Okoye BO, Parikh DH, Buick RG, Lander AD. Pyloric atresia: five new cases, a new association, and a review of the literature with guidelines. J Pediatr Surg. Aug 2000;35(8):1242-5

11. Roddy Isles, Head of Press (2005-05-12). "Dundee Scientists on road to cure for "Butterfly Children" condition". University of Dundee.

12. Suellen Hinde, Health reporter (2006-11-26). "Little girl's life of pain". HeraldSun.com.au.