Date of publication: 12/10/2011
Version: 1.1
Q84.5
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. Although changes to the nails most commonly lead to a diagnosis, it is painful calluses and blisters on the soles of the feet which usually cause most problems for the person with the disease.
There are different types of the disease, the most common being type 1 (Jadassohn-Lewandowsky type) and type 2 (Jackson-Lawler type). German dermatologists Josef Jadassohn and Felix Lewandowsky described type 1 in 1906. There is also a form of the disease called pachyonychia congenita tarda, where symptoms present first after childhood.
The disease is found in fewer than one per 100,000 inhabitants. In Sweden approximately 50 individuals have been diagnosed with pachyonychia congenita. However, as symptoms can vary there may be people with the disease who have not received a diagnosis.
Pachyonychia congenita is caused by a mutation in one of the genes which controls the production of (codes for) the protein keratin types 6, 6a, 16 or 17. Keratins are structural proteins which together form a stable network inside the horny cells of the epidermis. They make up most of the horny tissue which is constantly being renewed, giving strength and firmness to skin, hair and nails. A mutation in one of these keratin genes is enough to change the structure of a molecule so that it no longer forms part of the cell's structure. This results in the network becoming fragile and the horny tissue defective.
Depending on which of the keratin genes have mutated, the symptoms from skin, hair, nails and mucous membranes differ, causing various types of the disease. Pachyonychia congenita type 1 is caused by mutations in genes KRT6A or KRT16, while type 2 results from mutations in KRT6B or KRT17. Other diseases caused by mutations in the genes which control the formation of keratin (keratinopathies) are epidermolysis bullosa simplex and ichthyosis bullosa. In the Swedish Board of Health and Welfare's Database of Rare Diseases there is separate information material on epidermolysis bullosa and congenital ichthyosis.
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 down.
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 do not have an increased 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.
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 manifest in most people with the disease. Nail abnormalities are usually visible at birth or develop during the first months of life. The nail becomes progressively thicker, in extreme cases pointing 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 the only nails 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. 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 material under the calluses. This further increases pain when walking.
Horny material can also form around the hair follicles (keratosis follicularis), particularly on the 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 (Jadassohn-Lewandowsky 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 symptom specific to type 2 is the presence of natal teeth, these children later going on to develop widespread, painful sebaceous cysts (steatocystoma multiplex). There may also be congenital hair abnormalities resulting in sparse and often twisted hair (pili torti). Sebaceous cysts present during 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.
Others
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.
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 required to make a diagnosis of pachyonychia congenita. However, a microbial culture should be carried out as it can be useful in eliminating infections from possible diagnoses.
It is often possible to use a DNA-based analysis to confirm a diagnosis. If the mutation is known in the family, pre-natal diagnosis is possible.
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 urea, salicylic acid, propylene glycol and certain alpha hydroxy acids (AHAs) including lactic acid and glycolic acid.
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.
People 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. 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 mucous membranes. However, the effect is temporary and long-term treatment is associated with a risk of side-effects affecting for example the liver, skeleton and blood fats. A pregnant woman should never be given vitamin A medication because of the risk of damage to the foetus. If a pregnancy is planned, treatment with vitamin A medication should be stopped a very long time before conception as retinoids are broken down in the body very slowly.
Rough areas of skin are best treated by moisturisers (see above) while sebaceous cysts can be surgically removed if they become infected or cause other problems.
Problems in 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 (candidiasis) 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. 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.
Open, soft shoes or sandals are recommended. It is important to avoid becoming over-heated and sweating.
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 via 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.
Professor Anders Vahlquist, Dermatology Clinic, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. Tel: +46 18 611 00 00, fax: +46 18 611 26 80, email: anders.vahlquist@medsci.uu.se.
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.
Specialist physician, Dr Carl Swartling, Perspiration clinic, Sophiahemmet, Box 5605, SE-114 86 Stockholm, Sweden. Tel: +46 8 406 24 31, email: carl.swartling@sophiahemmet.se.
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The Swedish Pachyonychia Association. Contact person: Susanna Strokirk-Lilja, email: sannasl@bredband.net.
The Swedish Ichthyosis Association and the Epidermolysis Bullosa Association 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.se.
The Swedish Epidermolysis Bullosa Association (SEBF/D.E.B.R.A.Sweden). Chair is Therese Svedjeskog, Svedje 772, SE-860 35 Söråker, Sweden. Tel: +46 60 440 11, email: tezzan6699@yahoo.se, www.debra-sweden.org.
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A research team from the US and England, 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 the 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.
An information leaflet on pachyonychia congenita summarising the information in this database text is available free of charge from the customer service department of the Swedish National Board of Health and Welfare (in Swedish only, article number 2010-9-19). Address: SE-120 88 Stockholm, Sweden. Tel: +46 75 247 38 80, fax: +46 35 19 75 29, email: publikationsservice@socialstyrelsen.se. Postage will be charged for bulk orders.
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.
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.
Smith FJD, Kaspar RL, Schwartz ME, McLean WHI, Leachman SA. Pachyonychia Congenita. 2006 [updated 2009]. In: Pagon RA, Bird TC, Dolan CR,Stephens K, editors. GeneReviews. Seattle (WA): University of Washington, Seattle; 1993.
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 [Epub ahead of print].
Zamiri M, McLean WH, Hodgins MB, Munro CS. Pachyonychia congenita type 2: abnormal dentition extending into adulthood. Br J Dermatol 2008; 159: 500-501.
OMIM (Online Mendelian Inheritance in Man)
www.ncbi.nlm.nih.gov/omim
Search: pachyonychia congenita
GeneReviews (University of Washington)
www.genetests.org (find GeneReviews, then Titles)
Search: pachyonychia congenita
Pachonychia Congenita Project, www.pachyonychia.org.
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 Anders Vahlquist, Uppsala University Hospital, Sweden.
The relevant organisations for the disabled/patient associations have been given the opportunity to comment on the content of the text.
An expert group on rare diseases, affiliated with the University of Gothenburg, approved the material prior to publication.
Date of publication: 12/10/2011
Version: 1.1
Publication date of the Swedish version: 16/11/2010
For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 400, SE-405 30 Gothenburg, Sweden. Tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.