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Pachyonychia congenita

This is part of Rare diseases.

Diagnosis: Pachyonychia congenita

Synonyms: PC

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Date of publication: 2014-10-16
Version: 2.0

ICD-10

Q84.5

The disease

Pachyonychia congenita is a disease affecting the nails, skin, hair, teeth and on occasion the mucous membranes. The name refers to a congenital thickening of the nails (pachyonychia = thickened nails) and so describes only one of the symptoms. Painful calluses and blisters on the soles of the feet cause most problems for the person affected, although it is changes to the nails which most commonly lead to a diagnosis.

There are different types of the disease: type 1 (Jadassohn-Lewandowsky type) and type 2 (Jackson-Lawler type) being the most common. German dermatologists Josef Jadassohn och Felix Lewandowsky described type 1 in 1906. There is also a form of the disease called pachyonychia congenita tarda, where onset occurs is delayed until after childhood.

Occurrence

The disease is found in fewer than one in every 100,000 inhabitants. In Sweden approximately 50 individuals have been diagnosed with pachyonychia congenita. However, as symptoms can vary and sometimes be quite mild, there may be people with the disease who have not received a diagnosis.

Cause

Pachyonychia congenita is caused by a mutation in one of the genes which controls the production of (codes for) the keratin protein - types 6, 6a, 6b, 16 and 17. Keratines are structural proteins which together form a stable network inside the horny cells of the epidermis. This network makes up most of the mass of horny tissue. It is constantly being renewed, giving strength and firmness to skin, hair and nails. A mutation in one of these keratine genes is enough to change the structure of a molecule so that it no longer fits exactly in the network, thus interfering with the cell's structure. This results in the network becoming fragile and to defects in horny tissue.

Symptoms affecting skin, hair, nails and mucous membranes differ depending on which of the keratin genes have mutated, causing various types of the disease. Pachyonychia congenita type 1 is caused by mutations in either the KRT6A or KRT16 genes, while type 2 is caused by mutations in either KRT6B or KRT17.

Other diseases caused by mutations in the genes which control the formation of keratin (keratinopathies) are epidermolysis bullosa simplex and epidermolytic (bullous) ichthyosis. Separate information on these disorders is available in the rare disease database of the Swedish National Board of Health and Welfare.

Heredity

The inheritance pattern of pachyonychia congenita is usually autosomal dominant. This means that one of the parents has the disease, and so has one normal gene and one mutated gene. Sons and daughters of this parent have a 50 per cent risk of inheriting the disease. Children who do not inherit the mutated gene do not have the disease and do not pass it on.

Figure: Autosomal dominant inheritance

In approximately half of those with the disease, the condition is caused by a new mutation. This means that the genetic mutation occurs in an individual for the first time and is not inherited from either parent. Consequently, parents with a child with a new mutation generally have only a slight risk of having another child with the disorder. However, the new genetic mutation will be hereditary and an adult with this mutation risks passing on the mutated gene to his/her children.

In rare cases the pattern of inheritance is autosomal recessive.

Symptoms

The two most common types of pachyonychia congenita have many similar symptoms, including thickened nails and painful calluses on the soles of the feet. The clearest differences between the two types are that children with type 2 may have natal teeth and after puberty may develop painful sebaceous cysts.

Type 1 (Jadassohn-Lewandowsky type)

Nail abnormalities are usually visible at birth or develop during the first months of life. The nail bed becomes progressively thicker, lifting the nail up and in extreme cases causing it to point upwards at a sharp angle. The surface of the nail is normal but it is abnormally curved at the sides and is discoloured. Nails may be subject to fungal infections, which in the case of this disease are very painful.

The degree of severity varies, even among members of the same family. Toenails may be most affected. In such cases diagnosis may be delayed as the person affected may not seek help for the condition. When the hands are affected, nail thickening can be so extensive that it limits fine motor skills. The abnormal appearance of the nails can also cause social and psychological problems.

Nearly everyone with the condition develops blisters and calluses (keratoderma) on the soles of the feet or the palms of the hands. Foot problems are the main cause of disability. Symptoms are often noticed when the child learns to walk, but only after nail abnormalities present. Calluses are located on weight-bearing areas and are very painful. They may become so thick that they make walking or wearing ordinary shoes impossible. Increased levels of perspiration give rise to sticky blisters, consisting of softened horny tissue under the calluses. This further increases pain when walking.

Horny tissue can also form rough patches of hard skin around the hair follicles (keratosis follicularis) particularly on the outer surfaces of elbows and knees. This is most common during childhood and can be painful. When calluses develop on the scalp this may lead to hair loss (alopecia) and poor hair quality.

Whitish patches on the mucous membranes of the oral cavity and the throat (oral leukokeratosis) are often found in type 1, and may be mistaken for a fungal infection. In neonates this can lead to difficulties sucking. Abnormalities presenting in the larynx may cause hoarseness. In rare cases there may be changes in the cornea, affecting sight.

Type 2 (Jackson-Lawler type)

People with type 2 have the same symptoms as type 1, although the blisters and calluses on the soles of the feet may be less severe. Changes to the mucous membrane are unusual. A characteristic of type 2 is that the infant may be born with visible teeth. Sometimes there may also be congenital hair abnormalities where the hairs on the scalp are sparse and are often twisted round each other (pili torti) and later the children may develop scattered, painful sebaceous cysts (steatocystoma multiplex). Sebaceous cysts present at or after puberty. They may appear as lumps, often in the armpit and groin, sometimes reaching the size of a walnut. They may also become infected by skin bacteria.

Other features

Despite severe abnormalities in the horny tissue of the skin, nails, sebaceous glands and hair, and sometimes in the mouth, throat and mucous membranes of the eyes, there is no link to diseases in other organs. Life expectancy is normal.

Diagnosis

The diagnosis may be suspected if a young child has extensive nail abnormalities including thickened nail beds and unusually formed nail plates. It is important to exclude fungal infections, psoriasis or nail thickening as a result of injury. The disease may also be suspected if the child has blisters and calluses on the soles of the feet from a young age, or an unusually hoarse voice in combination with whitish deposits in the mouth.

A skin test (skin biopsy) is not usually of use in making a diagnosis of pachyonychia congenita. However, a microbiological culture should be carried out as it can be useful in eliminating infections from possible diagnoses.

DNA-based diagnosis is often possible. At the time of diagnosis it is important that the family is offered genetic counselling. Carrier and prenatal diagnosis, as well as pre-implantation genetic diagnosis (PGD) in association with IVF (in vitro fertilization), are available in families where the mutation is known.

Treatment/interventions

There is currently no cure for the disease and treatment focuses on alleviating individual symptoms.

In order to soften the skin and make it easier to file down, moisturising creams and ointments containing keratolytic agents are applied one or more times a day to the calluses and thickened areas on the soles of the foot. Keratolytics act as moisturisers and soften the horny outer layer of the skin. Common moisturisers are carbamide, salicylic acid, propylene glycol and certain alpha hydroxy acids (AHAs) including lactic acid and glycolic acid.

Where there are severe nail abnormalities, thickened nails on the feet can be filed and varnished by a medical chiropodist to make them stronger and more even. This treatment needs to be carried out regularly. A medical chiropodist can also treat calluses on the soles of the feet. Certain Swedish counties or regions offer medical chiropody services.

Those with the disease are recommended to use a foot bath to soften the skin before treatment on the soles of the feet, and to cut or file nails regularly. Infections under the nails are very painful and should be treated with internal medication. It is possible to remove nails surgically but in the case of fingers, the tops of the fingers are then unprotected and easily damaged.

Painful blisters and calluses on the soles of the feet can be treated with injections of the botulinum toxin. The treatment is carried out under local or general anaesthetic and inhibits sweating, which in turn reduces pain. It also makes it easier to remove the calluses by filing. The effects of each treatment usually last for between three and six months. It is important to reduce the pressure on the soles and toe nails. Referrals to orthopaedic workshops may be made to supply those with the disease with special shoes and foot supports. Protective socks and gloves can also be used. When pain in the soles of the feet is very severe a wheelchair can be used. The use of a special seat makes showering easier. People in severe pain may require regular doses of pain-killers to ease discomfort.

Tablets containing vitamin A (synthetic retinoids) can partly inhibit hardening of the skin and changes to the mucous membranes. However, the effect is temporary and long-term treatment is associated with a risk of serious side-effects affecting for example the liver, skeleton and blood fats. Pregnant women must never be treated with drugs containing vitamin A as retinoids cause severe birth defects. If a pregnancy is planned, treatment involving drugs containing vitamin A should be discontinued at least one year, or preferably two years, before the pregnancy as retinoids may be retained in the body for a long period of time.

Rough areas of skin are best treated by moisturisers (see above) while sebaceous cysts can be surgically removed if they often become infected or cause other problems.

Problems within the oral cavity are difficult to treat but regular and careful tooth brushing can prevent the formation of thick white deposits on the tongue and oral mucous membranes. Tooth brushing shall be carried out with care to avoid damage which may exacerbate the condition. It is important that any fungal infections are treated.

When the child starts nursery or school teachers, classmates and others should be informed about the cause of the abnormalities of skin and nails. It should be stressed that the disease is not infectious and that it is extremely painful, especially if the soles of the feet are affected. Children with nail abnormalities may find classmates avoiding them in games which require holding hands or touching. To prevent isolation and other social problems, age-appropriate information about the cause and treatment of the disease is important. Professional psychological and social support are important both for people with pachyonychia congenita and those close to them.

Practical advice

Open, soft shoes or sandals are recommended. It is important to avoid becoming over-heated and sweating.

National and regional resources in Sweden

Dermatologists have a broad knowledge of the disease. Specialist expertise is available at the Uppsala Genodermatosis Centre, Uppsala University Hospital, Sweden.

DNA analyses can be carried out at the Uppsala Genodermatosis Centre or at departments of clinical genetics at Sweden's university hospitals.

There is a specialist Perspiration Treatment Centre with experience in the use of the botulinum toxin at Sophiahemmet University College in Stockholm, Sweden.

Resource personnel

Specialist Physician, Dr Marie Virtanen, Dermatology Clinic, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. Tel: +46 18 611 00 00 , email: marie.virtanen@akademiska.se.

Associate Professor Carl Swartling, Svedklinikken, Hidros Denmark ApS, Hedegårdsvej 88, DK-2300 Copenhagen S, Denmark. Email: carl.swartling@svedklinikken.dk.

Courses, exchanges of experience, recreation

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Organizations for the disabled/patient associations etc. 

The Swedish Ichthyosis Association and the Epidermolysis Bullosa (EB) Association, Debra, have experience of similar diseases.

The Swedish Ichthyosis Association, Sturegatan 4C, Box 1386, SE-172 27 Sundbyberg, Sweden. Tel: +46 8 546 404 51, www.iktyos.nu.

The Swedish Epidermolysis Bullosa (EB) Association, Debra, www.ebforeningen.se.

Courses, exchanges of experience for personnel

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Research and development

A research team from the US and Scotland, with help from the non-profit organisation, PC Project, are collaborating in investigating the genetic mutations associated with the disease. Recently the first patient trials have been carried out, using siRNA technique to shut off the activity of the disease-related gene.

Perspiration-control treatment using the botulinum toxin has been developed in Sweden and research is under way into improving treatment as well as understanding why it gives effective and long-lasting pain relief in pachyonychia congenita.

Information material

Short summaries of all the database texts are available as leaflets, in Swedish only. These leaflets may be ordered or printed out. (See under "Mer hos oss" in the right hand column.)

The Pachyonychia Congenita Project is an American project with information in English, www.pachyonychia.org.

Literature

Ceyhan AM, Yildirim M, Akkaya VB, Yasan H. Persistent hoarseness in a patient with pachyonychia congenita: an early sign of laryngeal involvement. Int J Dermatol 2009; 48: 1346-1348.

Eliason MJ, Leachman SA, Feng BJ, Schwartz ME, Hansen CD. A review of the clinical phenotype of 254 patients with genetically confirmed pachyonychia congenita. J Am Acad Dermatol. 2012; 67: 680-686.

Goldberg I, Fruchter D, Meilick A, Schwartz ME, Sprecher E. Best treatment practices for pachyonychia congenita. J Eur Acad Dermatol Venereol. 2014; 28: 279-285.

Gruber R, Wilson NJ, Smith FJ, Grabher D, Steinwender L, Fritsch PO et al. Increased pachyonychia congenita severity in patients with concurrent keratin and filaggrin mutations. Br J Dermatol 2009; 161: 1391-1395.

Jadassohn J, Lewandowsky F. Pachyonychia congenita. In: Jakobs Ikonographia Dermatologica. Berlin: Urban and Schwarzenberg (pub.) 1; 1906: 29.

Leachman SA, Kaspar RL, Fleckman P, Florell SR, Smith FJ, McLean WH et al. Clinical and pathological features of pachyonychia congenita. J Investig Dermatol Symp Proc 2005; 10: 3-17.

Milstone LM, Fleckman P, Leachman SA, Leigh IM, Paller AS, van Steensel MA et al. Treatment of pachyonychia congenita. J Investig Dermatol Symp Proc 2005; 10: 18-20.

Smith FJ, Liao H, Cassidy AJ, Stewart A, Hamill KJ, Wood P et al. The genetic basis of pachyonychia congenita. J Investig Dermatol Symp Proc 2005; 10: 21-30.

Swartling C, Karlqvist M, Hymnelius K, Weis J, Vahlquist A. Botulinum toxin in the treatment of sweat-worsened foot problems in patients with epidermolysis bullosa and pachyonychia congenita. Br J Dermatol 2010; 163: 1072-1076.

Zamiri M, McLean WH, Hodgins MB, Munro CS. Pachyonychia congenita type 2: abnormal dentition extending into adulthood. Br J Dermatol 2008; 159: 500-501.

Database references

OMIM (Online Mendelian Inheritance in Man)
www.ncbi.nlm.nih.gov/omim 
Search: pachyonychia congenita

GeneReviews (University of Washington)
www.genetests.org (select "GeneReviews", then "Titles")
Search: pachyonychia congenita

Document information

The Swedish Information Centre for Rare Diseases produced and edited this information material.

The medical expert who wrote the draft of this information material is Professor Emeritus Anders Vahlquist, Uppsala University, Sweden.

An expert group on rare diseases, affiliated with the University of Gothenburg, approved the material prior to publication.

Date of publication: 2014-10-16
Version: 2.0
Publication date of the Swedish version: 2014-06-23

For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 422, SE-405 30 Gothenburg, Sweden. Tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.

 

About the database

This knowledge database provides information on rare diseases and conditions. The information is not intended to be a substitute for professional medical care, nor is it intended to be used as a basis for diagnosis or treatment.