Kindler epidermolysis bullosa

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Kindler epidermolysis bullosa (or Kindler EB) is a rare type of epidermolysis bullosa, which is a group of genetic conditions that cause the skin to be very fragile and to blister easily.

From early infancy, people with Kindler EB have skin blistering, particularly on the backs of the hands and the tops of the feet. The blisters occur less frequently over time, although repeated blistering on the hands can cause scarring that fuses the skin between the fingers and between the toes. Affected individuals also develop thin, papery skin starting on the hands and feet and later affecting other parts of the body; changes in skin coloring; and small clusters of visible blood vessels just under the skin (telangiectases). This combination of features is known as poikiloderma. In some affected individuals, the skin on the palms of the hands and soles of the feet thickens and hardens (hyperkeratosis). Kindler EB can also cause people to be highly sensitive to ultraviolet (UV) rays from the sun and to sunburn easily.

Kindler EB can also affect the moist lining (mucosae) of the mouth, eyes, esophagus, intestines, genitals, and urinary system, causing these tissues to be very fragile and easily damaged. Affected individuals commonly develop severe gum disease that can lead to early tooth loss. The moist tissues that line the eyelids and the white part of the eyes (the conjunctiva) can become inflamed (conjunctivitis), and damage to the clear outer covering of the eye (the cornea) can affect vision. Narrowing (stenosis) of the esophagus, which is the tube that carries food from the mouth to the stomach, causes difficulty with swallowing that worsens over time. Some affected individuals develop health problems related to inflammation of the colon (colitis) or damage to the mucosa in the vagina, the anus, or the tube that carries urine from the bladder out of the body (the urethra).

Kindler EB increases the risk of developing a form of cancer called squamous cell carcinoma. This type of cancer arises from squamous cells, which are found in the outer layer of skin (the epidermis) and in the mucosae. In people with Kindler EB, squamous cell carcinoma occurs most often on the skin, lips, and the lining of the mouth (oral mucosa).

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Kindler EB results from variants (also known as mutations) in the FERMT1 gene. This gene provides instructions for making a protein known as kindlin-1. This protein is found in epithelial cells, which are the cells that line the surfaces and cavities of the body. In the skin, kindlin-1 plays a critical role in specialized cells called keratinocytes, which are the major component of the epidermis. Kindlin-1 is involved in several important cell functions, including cell growth and division (proliferation), the attachment of cells to the underlying network of proteins and other molecules (cell-matrix adhesion), and the movement (migration) of cells.

Most variants in the FERMT1 gene prevent the production of any functional kindlin-1. A lack of this protein disrupts many essential cell functions. For example, keratinocytes without kindlin-1 have an abnormal structure and cannot grow or divide normally. They are also less able to attach the epidermis to the underlying layer of skin (the dermis). These changes make the skin fragile and prone to blistering. Similarly, a lack of kindlin-1 in epithelial cells of the mucosae causes damage that makes these tissues extremely fragile. It is unclear how a shortage of kindlin-1 is related to squamous cell carcinoma in people with Kindler EB.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have variants. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Kindler EB appears to be rare. About 250 cases have been reported worldwide.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal blistering of the skin · Very frequent (99-80%)

The presence of one or more bullae on the skin, defined as fluid-filled blisters more than 5 mm in diameter with thin walls.

Cheilitis · Very frequent (99-80%)

Inflammation of the lip.

Cutaneous photosensitivity · Very frequent (99-80%)

An increased sensitivity of the skin to light. Photosensitivity may result in a rash upon exposure to the sun (which is known as photodermatosis). Photosensitivity can be diagnosed by phototests in which light is shone on small areas of skin.

Erythema · Very frequent (99-80%)

Redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin.

Palmoplantar keratoderma · Very frequent (99-80%)

Abnormal thickening of the skin of the palms of the hands and the soles of the feet.

Poikiloderma · Very frequent (99-80%)

Poikiloderma refers to a patch of skin with (1) reticulated hypopigmentation and hyperpigmentation, (2) wrinkling secondary to epidermal atrophy, and (3) telangiectasias.

Aplasia/Hypoplasia of the skin · Very frequent (99-80%)

Abnormal toenail morphology · Frequent (79-30%)

An anomaly of the toenail.

Other findings in the same source

From: Orphanet

Additional reported features include Abnormality of dental enamel (Frequent (79-30%)); Abnormality of skin pigmentation (Frequent (79-30%)); Camptodactyly of finger (Frequent (79-30%)); Carious teeth (Frequent (79-30%)); Colitis (Frequent (79-30%)); Dysphagia (Frequent (79-30%)); Esophageal stricture (Frequent (79-30%)); Esophagitis (Frequent (79-30%)); Finger syndactyly (Frequent (79-30%)); Gingivitis (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Kindler epidermolysis bullosa is Dermatology, with a dermatologist as the relevant type of clinician. Dermatologist; paediatric services for children as appropriate.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which features of the skin, hair or nails distinguish the possibilities?
• Would photographs over time help document the changes?
• What should be expected from treatment, and how will irritation or other adverse effects be managed?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Kindler epidermolysis bullosa. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.