What are the other Names for this Condition? (Also known as/Synonyms)

• Nagashima-Type PPK
• NPPK (Nagashima-Type Palmoplantar Keratoderma)

What is Nagashima-Type Palmoplantar Keratoderma? (Definition/Background Information)

• Nagashima-Type Palmoplantar Keratoderma (NPPK) is an uncommon form of hereditary diffuse palmoplantar keratoderma (PPK) that is transmitted in an autosomal recessive manner. The condition manifests during early childhood/infancy, and is characterized by widespread red skin, skin thickening that extends beyond the palms and soles, and excessive sweating
• Hereditary diffuse palmoplantar keratoderma is a type of palmoplantar keratoderma (PPK) caused by genetic mutations. PPK is a benign skin condition, wherein there is thickening of skin (keratoderma) of the palms and/or soles. PPK is considered to be a pattern of skin findings and not a condition in itself. The abnormal skin thickening can be focal (localized), widespread (diffused), or punctate type (appearing as tiny bumps)
• The skin signs and symptoms of Nagashima-Type Palmoplantar Keratoderma are typically non-progressive; an involvement of other body systems or organs is not noted. The treatment involves the use of moisturizers, skin softeners, and systemic medications. The prognosis of NPPK is generally good in most cases

Who gets Nagashima-Type Palmoplantar Keratoderma? (Age and Sex Distribution)

• Nagashima-Type Palmoplantar Keratoderma is a congenital disorder; the signs and symptoms are predominantly noted in infants and young children within the first 36 months of life (by age 3)
• The condition affects both males and females
• Cases of Nagashima-Type PPK are common among the Japanese and Chinese populations. This form of PPK is very rare in Western countries

What are the Risk Factors for Nagashima-Type Palmoplantar Keratoderma? (Predisposing Factors)

• The risk factor for Nagashima-Type Palmoplantar Keratoderma (NPPK) includes a positive family history of the condition
• Children born to consanguineous partners or spouses have a high risk for the condition
• Asian populations, mostly belonging to Japan and China, report a very high incidence of NPPK

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Nagashima-Type Palmoplantar Keratoderma? (Etiology)

• Nagashima-Type Palmoplantar Keratoderma (NPPK) is caused by genetic abnormalities which are passed down (through families) in an autosomal recessive manner
• It is caused by mutations involving the SERPINB7 gene that regulates protease inhibitors, which protects cells from mechanical stress-induced injury
• Due to this, the manifestation of signs and symptoms of NPPK typically involves the pressure-bearing or mechanical stress bearing areas such as the palms, soles, elbows, and knees

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive gene, there is a 25% chance a child getting the defective gene from each parent. These offspring will have the disease or condition. There is a 25 % chance that they will inherit the gene from only one parent, so they will be unaffected and not pass the gene on to their children. There is a 50 % that they will get the gene from one parent and not the other. In the very rare situation where both parents have an autosomal recessive condition, all their offspring will have both genes, and hence the condition.

What are the Signs and Symptoms of Nagashima-Type Palmoplantar Keratoderma?

In general, the signs and symptoms associated with Nagashima-Type Palmoplantar Keratoderma may include:

• Young children present reddish skin discoloration on the palms of the hands and soles of the feet
• This forms abnormally-thickened skin on the palms and soles that involves the entire palm and sole (diffused); the fingers and toes are usually affected
• Presence of mild to moderate transgrediens (i.e., contiguous extension of skin thickening beyond the palms and soles), which does not get worse with time
• The fingers, toes, elbows, and knees present skin lesions; the pressure-bearing/frictional regions are usually affected
• When immersed in water for a short period of time, the affected skin turns white and spongy
• Hyperhidrosis, excessive sweating, of the palms and soles
• No itching is noted
• Normal activities that involve the use of one’s hands and feet may be affected
• No other body organs or systems are known to be affected; the condition is non-syndromic (isolated occurrence)

How is Nagashima-Type Palmoplantar Keratoderma Diagnosed?

The diagnosis of Nagashima-Type Palmoplantar Keratoderma may involve:

• A complete evaluation of medical history along with a thorough examination of the skin lesions by a dermatologist
• The healthcare provider may also ask many questions related to the individual’s age, family medical history, current medications, cosmetics, body lotions used, other medical conditions, infections, etc.
• Blood tests that may include complete blood count (CBC) test, basic metabolic panel, and liver function test (LFT)
• Dermoscopy: It is a diagnostic tool where a dermatologist examines the skin using a special magnified lens
• Wood’s lamp examination: In this procedure, the healthcare provider examines the skin using ultraviolet light. It is performed to examine the change in skin pigmentation
• Molecular genetic testing to identify the gene involved
• Skin biopsy: A skin tissue biopsy is performed and sent to a laboratory for a pathological examination. The pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Nagashima-Type Palmoplantar Keratoderma?

The complications associated with Nagashima-Type Palmoplantar Keratoderma are usually not very significant than other PPK forms since it is a non-progressive condition. The complications may include:

• Emotional stress
• Cosmetic concerns
• Secondary bacterial and fungal infections such as athlete’s foot
• Disruption of normal life and activities if the condition is severe
• Development of skin cancer (acral lentiginous melanoma) has been very rarely reported
• Lack of treatment response
• Treatment complications and medication side effects

How is Nagashima-Type Palmoplantar Keratoderma Treated?

There is no cure for Nagashima-Type Palmoplantar Keratoderma, and the condition is managed through supportive and symptomatic treatment (skin softening treatment), which may involve the following measures:

• Use of moisturizing creams and lotions; topical aminoglycoside is known to be somewhat effective in treating NPPK
• Use of oral medication, such as acitretin, and systemic retinoids
• Administration of keratolytics (medicine containing salicylic acid or urea)
• Vitamin D supplementation
• Phototherapy
• Surgical debridement (removal of thickened skin), if required

Regular follow up visits with the healthcare provider is important and recommended.

How can Nagashima-Type Palmoplantar Keratoderma be Prevented?

Currently, Nagashima-Type Palmoplantar Keratoderma is a genetic disorder that cannot be prevented. However, the following may be considered:

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited genetic disorders such as hereditary palmoplantar keratoderma

What is the Prognosis of Nagashima-Type Palmoplantar Keratoderma? (Outcomes/Resolutions)

• The prognosis of Nagashima-Type Palmoplantar Keratoderma is dependent upon the severity of the signs and symptoms, associated complications, and treatment response
• In most individuals, the condition is mild and non-progressive, resulting in overall better outcomes

Additional and Relevant Useful Information for Nagashima-Type Palmoplantar Keratoderma:

Cleaning the skin too hard with strong chemicals or soaps may aggravate the skin condition. Care must be taken avoid strong soaps and chemicals that could potentially worsen the condition.