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Paronychia congenita

What is paronychia congenita

Pachyonychia congenita is the name given to a group of rare, inherited autosomal dominant disorders that primarily affects the skin and nails keratinization. Keratinization is the process by which keratin (scale) is formed and deposited in the outer most layer of the skin. The signs and symptoms of paronychia congenita usually become apparent within the first few years of life. Almost everyone with pachyonychia congenita shows some signs of hypertrophic nail dystrophy, which causes the fingernails and toenails to become thick and abnormally shaped. Most affected children also develop very painful blisters and calluses on the soles of the feet and, less commonly, on the palms of the hands. This condition is known as palmoplantar keratoderma. Severe blisters and calluses on the feet usually first begin to form in childhood when they first start to walk, and can make walking painful or impossible.

Pachyonychia congenita occurs when there is a mutation in the keratin genes encoding keratin, KRT6A, KRT6B, KRT6C, KRT16 and KRT17 1. Nearly 100 mutations have been described by the International Pachyonychia Congenita Research Registry 2. The mutations cause the skin to be more fragile than usual.

Prior to genetic testing, some patients were diagnosed with pachyonychia congenita that actually did not have this disorder. Mutations in other keratin genes can lead to similar skin conditions.

Pachyonychia congenita can have several additional features, which vary among affected individuals. These features include thick, white patches on the tongue and inside of the cheeks (oral leukokeratosis); bumps called follicular keratoses that develop around hair follicles on the elbows, knees, and waistline; cysts in the armpits, groin, back, or scalp; and excessive sweating on the palms and soles (palmoplantar hyperhidrosis). Some affected individuals also develop widespread cysts called steatocystomas, which are filled with an oily substance called sebum that normally lubricates the skin and hair. Some babies with pachyonychia congenita have prenatal or natal teeth, which are teeth that are present at birth or in early infancy. In some cases, pachyonychia congenita can affect the voice box (larynx), causing hoarseness or breathing problems.

Researchers used to distinguish pachyonychia congenita as one of two types, paronychia congenita-1 or paronychia congenita-2, based on the genetic cause and pattern of signs and symptoms. However, as more affected individuals were identified, it became clear that the features of the two types overlapped considerably. Now researchers prefer a description of pachyonychia congenita based on the gene that is altered.

Although the prevalence of pachyonychia congenita is unknown, it is a rare disorder with several thousand people likely affected worldwide 3.

Paronychia congenita does not affect lifespan, but almost all patients experience constant pain.

Figure 1. Paronychia congenita

Paronychia congenita

Footnote: Common findings of pachyonychia congenita include: thickened and dystrophic nails (both fingernails and toenails) (a-c); bullae (usually on the pressure points of the heels and soles); hyperkeratosis (d-e); cysts (f); and oral leukokeratosis (g).

[Source 4 ]

Classification of pachyonychia congenita

Pachyonychia congenita was traditionally classified into Type 1 and Type 2, according to the clinical features. Classification now depends on which keratin gene has the specific mutation 5.

Clinical featuresPercent affected with each genetic mutation
K6AK6BK6CK16K17
Thick toenails99%98%56%95%99%
Thick fingernails99%51%061%87%
Plantar keratoderma89%98%94%100%80%
Plantar pain96%100%100%97%89%
Palmar keratoderma54%41%19%81%51%
Cysts68%71%25%26%92%
Follicular hyperkeratosis62%47%014%68%
Natal or prenatal teeth2%00077%
Oral leukokeratosis88%31%19%41%27%

Pachyonychia congenita causes

Mutations in several genes, including KRT6A, KRT6B, KRT6C, KRT16, and KRT17, can cause pachyonychia congenita. All of these genes provide instructions for making tough, fibrous proteins called keratins. These proteins form networks that provide strength and resilience to the tissues that make up the skin, hair, and nails.

When pachyonychia congenita is caused by mutations in the KRT6A gene, it is classified as PC-K6a. Similarly, KRT6B gene mutations cause PC-K6b, KRT6C gene mutations cause PC-K6c, KRT16 gene mutations cause PC-K16, and KRT17 gene mutations cause PC-K17.

Mutations in keratin genes alter the structure of keratin proteins, which prevents these proteins from forming strong, stable networks within cells. Without this network, skin cells become fragile and are easily damaged, making the skin less resistant to friction and minor trauma. Even normal activities such as walking can cause skin cells to break down, resulting in the formation of severe, painful blisters and calluses. Defective keratins also disrupt the growth and function of cells in the hair follicles and nails, resulting in the other features of pachyonychia congenita.

Paronychia congenita inheritance pattern

Pachyonychia congenita is considered an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In about 60 to 70 percent of all cases, an affected person inherits the mutation from one affected parent. Thirty to 40 percent of cases result from a new (de novo) mutation in the gene that occurs during the formation of reproductive cells (eggs or sperm) or in early embryonic development. These cases occur in people with no history of the disorder in their family.

Often autosomal dominant conditions can be seen in multiple generations within the family. If one looks back through their family history they notice their mother, grandfather, aunt/uncle, etc., all had the same condition. In cases where the autosomal dominant condition does run in the family, the chance for an affected person to have a child with the same condition is 50% regardless of whether it is a boy or a girl. These possible outcomes occur randomly. The chance remains the same in every pregnancy and is the same for boys and girls.

  • When one parent has the abnormal gene, they will pass on either their normal gene or their abnormal gene to their child. Each of their children therefore has a 50% (1 in 2) chance of inheriting the changed gene and being affected by the condition.
  • There is also a 50% (1 in 2) chance that a child will inherit the normal copy of the gene. If this happens the child will not be affected by the disorder and cannot pass it on to any of his or her children.

There are cases of autosomal dominant gene changes, or mutations, where no one in the family has it before and it appears to be a new thing in the family. This is called a de novo mutation. For the individual with the condition, the chance of their children inheriting it will be 50%. However, other family members are generally not likely to be at increased risk.

Figure 2 illustrates autosomal dominant inheritance. The example below shows what happens when dad has the condition, but the chances of having a child with the condition would be the same if mom had the condition.

Figure 2. Paronychia congenita autosomal dominant inheritance pattern

Paronychia congenita autosomal dominant inheritance pattern

People with specific questions about genetic risks or genetic testing for themselves or family members should speak with a genetics professional.

Resources for locating a genetics professional in your community are available online:

Pachyonychia congenita symptoms

Pachyonychia congenita affects the skin (especially palms and soles), nails and mucous membranes. Specific features depend on which keratin gene is involved.

Clinical features of pachyonychia congenita:

  • Palms and soles
    • Thickened or calloused palms and soles (palmoplantar hyperkeratosis or keratoderma, particularly focal palmoplantar keratoderma), resulting in difficulty walking
    • Focal palmoplantar keratoderma may be the only feature of pachyonychia congenital in patients with mutations of K6C.
    • Pain is common and can be very severe, particularly in patients with mutations of K6a and K16
    • Hyperhidrosis (excessive sweating)
    • Blisters precipitated by friction and warm weather
  • Nails
    • Nail changes are most severe with mutations of K6a and K16
    • Abnormalities of nails are apparent early in life
    • Nails are thickened (pachyonychia), often with brownish discolouration
    • All fingernails are commonly involved; toenails to a lesser degree. Specific K16 mutations do not affect fingernails
  • Cysts
    • Steatocystoma and pilosebaceous cysts are common, particularly in patients with mutations of K17 and to a lesser extent, K16A
    • Cysts may or may not be painful
  • Dry skin
    • Friction sites such as knees and elbows may be dry due to scale around hair follicles (follicular hyperkeratosis)
    • Tends to become less obvious in adult life
  • Mouth
    • White patches on tongue and inside cheeks (leukokeratosis)
    • Sores at sides of mouth (angular cheilitis)
    • Tooth abnormalities (natal or prenatal teeth)
  • Larynx
    • Hoarseness may occur

The most common features of pachyonychia congenita include:

  1. Thickened nails (hypertrophic nail dystrophy or pachy-onychia) although not all nails are affected in all patients with pachyonychia congenita.
  2. Painful calluses and blisters on the soles of the feet (focal plantar hyperkeratosis). Pain is one of the distinct characteristics of pachyonychia congenita. Blisters are found under the callus in pachyonychia congenita patients. Calluses may also form on the palms of the hands (palmar hyperkeratosis).
  3. Cysts of various types (including steatocystoma and pilosebaceous cysts). In some forms of pachyonychia congenita, this is the most dominant, painful, and problematic characteristic.
  4. Follicular hyperkeratosis (bumps around hairs at friction sites such as waist, hips, knees, elbows). Most common in children and lessens after teenage years.
  5. Leukokeratosis of the oral mucosa (white film on tongue and inside cheeks). This is not painful, but is often misdiagnosed as thrush or as leukoplakia.

Less common features of pachyonychia congenita include:

  1. Sores at the corner of the mouth (angular cheilitis).
  2. Teeth at or before birth (natal or pre-natal teeth). This is found in one subset of pachyonychia congenita.
  3. Laryngeal involvement with a white keratin film on the larynx. This results in a hoarse cry or a hoarse voice and is found in only a few patients.
  4. Intense pain on first bite (‘first bite syndrome’). The pain is near the jaw or ears and lasts 15–25 seconds when beginning to eat or swallow. This is more common in younger children and is often confused with ear problems.

Pachyonychia congenita diagnosis

Pachyonychia congenita is usually diagnosed by its clinical appearance.

Skin biopsy of the affected tissues will only show nonspecific changes.

Molecular genetic studies can be done by specialist laboratories to detect mutations in the affected keratin genes. A genetic counsellor can advise whether the test is available in your area. Testing is available free of cost via Pachyonychia Congenita Project.

Prenatal testing is sometimes offered to pregnant women when they or a partner is affected by pachyonychia congenita. Pre-implantation diagnosis of ‘test-tube’ embryos has also been reported.

Pachyonychia congenita treatment

Unfortunately there is as yet no cure for pachyonychia congenita. The effectiveness of treatment depends on the severity of the specific problem.

The most effective factor for pachyonychia congenita care is frequent and consistent trimming of the nails and the calluses on the feet and sometimes on the palms. Known as “debridement,” this trimming must not leave the nails too short or too long, and the callus not too thick and not too thin.

  • SOAK before trimming calluses or nails. Many patients use plain water, soapy water, or a bubble bath for children. Others add things such as salt, epsom salts, propylene glycol, or a small amount of bleach or another disinfectant. Vinegar may soften skin, but it does not eliminate germs. The most effective way to reduce infections is to use a “bleach bath” (one capful of household bleach to a gallon of water). Using a bleach bath can reduce infections in feet, hands, and nails.
  • TRIM nails and calluses by using clippers, razor blades, or a small grinder. To avoid infections, it is important not to trim too deeply and to be certain both the tools and the nails/skin are clean/sterile. Each patient has their own “just right” level for trimming. Trimming nails should never cause pain. Calluses that are either too thick or too thin both can cause increased pain.
  • MOISTURIZERS are used by almost all patients. As a rule: a gel will dry the skin, a lotion will moisturize somewhat, but a cream is more moisturizing. An ointment base (like petroleum jelly) is the most moisturizing and is used by the majority of pachyonychia congenita patients.

Most patients care for their pachyonychia congenita condition at home. Obviously, trimming should be done with clean tools and clean nails and skin. Because trimming removes protective skin or nail and exposes the area to outside germs, these precautions are important both for comfort and to lessen the chance of infection. Whether done by the patient or by professionals, this regular trimming to the best length and thickness is basic to lessen pain and prevent infections which increase with either overgrown or over-trimmed areas.

When inflamed, cysts may need to be drained or removed by a physician. Again, opening cysts exposes the area to outside germs and care is needed to avoid infection.

As the hyperkeratosis may occur as a reaction to trauma (stress or pressure), some patients have found ways to lesson the trauma to feet and hands through special shoes, socks, gloves, insoles or orthotics, canes, crutches, etc.

Treatment of keratoderma might include:

  • Emollients
  • Keratolytics, such as salicylic acid ointment, urea cream or other forms of heel balm. Keratolytic therapy is a treatment used for conditions such as dermatitis, psoriasis, eczema, corns, and calluses to help loosen and shed hard, scaly skin. In this therapy, acid medicine — such as salicylic acid — is put on the lesion. Keratolytic medicines cause the outer layer of the skin to loosen and shed. Keratolytics can also be used to soften keratin, a major component of the skin. This serves to improve the skin’s moisture-binding capacity. Such agents (keratolytics) include urea, lactic acid, and allantoin, and cause calluses and thick horny skin to swell, soften, and then peel or scale off. These have active ingredients such as salicylic acid or glycolic acid. While keratolytic therapy has been helpful for some patients, pachyonychia congenita generally produces more overgrowth of callus and nails than this type of therapy can control. While the treatment may help (especially for follicular hyperkeratosis bumps on knees, elbows, waist, and arms), no adult pachyonychia congenita patient uses this as the means of reducing hyperkeratosis and most find little benefit in keratolytics. Most pachyonychia congenita patients trim nails and calluses and use a basic moisturizer such as Vaseline as their standard care.
    • Salicylic acid — also known as 2-hydroxybenzoic acid, one of several beta hydroxy acids — is a key ingredient in many skin-care products for the treatment of acne, psoriasis, calluses, corns, keratosis pilaris, and warts (Adapted from Wikipedia at http://en.wikipedia.org/wiki/Salicylic_acid). Salicylic acid formulations come in gel, ointments, creams, and lotions. Those with over 5% salicylic acid are usually prescription only (and you must have a physician’s order), and those at 3% or so are over-the-counter and can be purchased without a doctor’s order.
    • Urea is an emollient (skin softening agent) which helps to moisturize the skin and is used in topical dermatological products to promote rehydration of the skin. If covered by an occlusive dressing, 40% urea preparations may be used as keratolytic agents (for debridement of nails and removal of calluses).
  • Mechanical debridement
  • Bleach baths to reduce infection
  • Pain relief
  • Oral retinoids, particularly acitretin.
  • Surgical removal of nails (ablation) and destruction of the nail matrix (where the nail originates) is a more permanent option, although it may need to be repeated if the matrix is not completely destroyed or removed. Based on data reported in the Ipachyonychia congenitaRR, the outcome has not been completely satisfactory for most patients. Surgical removal of the plantar skin has been reported for only one pachyonychia congenita patient and the results are mixed.

Thickened nails should be regularly trimmed.

Experimental treatments are being offered to some patients with pachyonychia congenita as part of clinical trials of novel agents such as mTOR inhibitors (eg, sirolimus).

Medications

The following drugs and treatments are listed alphabetically. Although most of these have been prescribed for or tried by pachyonychia congenita patients, there is no report of successful long-term benefit from these treatments, and none of these treatments are recommended by a majority of pachyonychia congenita patients or physicians specializing in pachyonychia congenita.

  • Botulin toxin (Botox, Dysport) has been injected in the soles of feet of several pachyonychia congenita patients to reduce pain. It is thought the mechanism reduces hyperhidrosis. A qualified clinical study has not been completed.
  • Fluorouracil — an anti-neoplastic agent which inhibits cell growth and proliferation — has also been prescribed for pachyonychia congenita. There is no clear evidence of benefit for pachyonychia congenita patients.
  • Oral retinoids, which regulate the differentiation and proliferation of skin cells, have been prescribed for pachyonychia congenita patients. Those frequently prescribed for pachyonychia congenita include etretinate, isotretinoin, and acitretin. Based on statistics from the Ipachyonychia congenitaRR, most patients find that these drugs thin the calluses but often cause increased pain. For many patients, the side effects are too severe and the benefits too slight to continue use of these drugs.

Only a very few patients have continued to use these drugs, and those who have had success seem to have worked very closely with a physician to constantly regulate the dose or to start/stop the drug under frequent physician care. No data has been collected on the effect these drugs may have on pachyonychia congenita cysts, although certainly these drugs are used for acne. The side effects make long-term use problematic.

  • Phenytoin (US trade name is Dilantin) is an anti-epileptic agent that also prevents the breakdown of collagen and has been used for treatment of pachyonychia congenita. Side effects can be severe. There is no clear evidence of benefit for pachyonychia congenita patients.

Paronychia congenita prognosis

Pachyonychia congenita is not associated with a reduced lifespan.

References
  1. Genetics of PC. https://www.pachyonychia.org/pc_genetics
  2. Pachyonychia Congenita Project. https://www.pachyonychia.org/pc_genetics
  3. Pachyonychia congenita. https://ghr.nlm.nih.gov/condition/pachyonychia-congenita
  4. Smith FJD, Hansen CD, Hull PR, et al. Pachyonychia Congenita. 2006 Jan 27 [Updated 2017 Nov 30]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1280
  5. Pachyonychia Congenita Project. https://www.pachyonychia.org/
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