Mal de Meleda

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Mal de Meleda is a rare skin disorder that begins in early infancy. Affected individuals have a condition known as palmoplantar keratoderma, in which the skin of the palms of the hands and soles of the feet becomes thick, hard, and callused. In mal de Meleda, the thickened skin is also found on the back of the hands and feet and on the wrists and ankles. In addition, affected individuals may have rough, thick pads on the joints of the fingers and toes and on the elbows and knees. Some people with mal de Meleda have recurrent fungal infections in the thickened skin, which can lead to a strong odor. Other features of this disorder can include short fingers and toes (brachydactyly), nail abnormalities, red skin around the mouth, and excessive sweating (hyperhidrosis).

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mal de Meleda is caused by mutations in the SLURP1 gene. This gene provides instructions for making a protein that interacts with other proteins, called receptors, and is likely involved in signaling within cells. Studies show that the SLURP-1 protein can attach (bind) to nicotinic acetylcholine receptors (nAChRs) in the skin. Through interaction with these receptors, the SLURP-1 protein is thought to be involved in controlling the growth and division (proliferation), maturation (differentiation), and survival of skin cells.

Mutations in the SLURP1 gene lead to little or no SLURP-1 protein in the body. It is unclear how a lack of this protein leads to the skin problems that occur in mal de Meleda. Researchers speculate that without SLURP-1, the activity of genes controlled by nAChR signaling is altered, leading to overgrowth of skin cells or survival of cells that normally would have died. The excess of cells can result in skin thickening. It is unclear why skin on the hands and feet is particularly affected.

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 mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Mal de Meleda is a rare disorder; its prevalence is unknown. The disorder was first identified on the Croatian island of Mljet (called Meleda in Italian) and has since been found in populations 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 foot morphology · Very frequent (99-80%)

An abnormality of the skeleton of foot.

Abnormality of the hand · Very frequent (99-80%)

An abnormality affecting one or both hands.

Inflammatory abnormality of the skin · Very frequent (99-80%)

The presence of inflammation of the skin. That is, an abnormality of the skin resulting from the local accumulation of fluid, plasma proteins, and leukocytes.

Nonepidermolytic palmoplantar keratoderma · Very frequent (99-80%)

Abnormal thickening of the skin on the palms and soles charactersized by hyperkeratosis of the stratum corneum with no evidence of epidermolysis characteristic of epidermolytic hyperkeratosis.

Palmoplantar keratoderma · Very frequent (99-80%)

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

Superficial dermal perivascular inflammatory infiltrate · Very frequent (99-80%)

Numerous lymphocytes surrounding blood vessels in the superficial part of the dermis.

Autoamputation · Frequent (79-30%)

Auto-amputation is the spontaneous detachment of an appendage from the body due to long standing pathology.

Diffuse palmoplantar kyperkeratosis · Frequent (79-30%)

Diffuse abnormal thickening of the skin on the palms and soles.

Epidermal acanthosis · Frequent (79-30%)

Diffuse hypertrophy or thickening of the stratum spinosum of the epidermis (prickle cell layer of the skin).

Erythema · Frequent (79-30%)

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

Flexion contracture · Frequent (79-30%)

A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.

Hyperhidrosis · Frequent (79-30%)

Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather.

Hyperkeratosis with erythema · Frequent (79-30%)

Ichthyosis · Occasional (29-5%)

An abnormality of the skin characterized the presence of excessive amounts of dry surface scales on the skin resulting from an abnormality of keratinization.

Other findings in the same source

From: Orphanet

Additional reported features include Lichenoid skin lesion (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Mal de Meleda 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 Mal de Meleda. 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.