Date of publication: 2009-06-24
Version: 4.1
Ichthyosis is a group of disorders consisting of more than 20 different hereditary conditions, all characterized by a significantly increased thickness of the cornified layer of the skin (the stratum corneum), and scaling of large skin areas.
Using a simplified system of classification, it is possible to divide the ichthyoses into five main groups:
- Common ichthyosis (ichthyosis vulgaris)
- X-linked ichthyosis
- Lamellar ichthyosis (ichthyosiform erythroderma)
- Bullous ichthyosis
- Ichthyosis associated with a syndrome such as Sjögren-Larsson syndrome, Refsum disease or Netherton syndrome (information on each of these disorders is available in the Swedish rare disease database).
The name comes from the Greek word ichthys meaning fish. There are several very old descriptions of individuals who are likely to have been affected by ichthyosis. One of the first scientific descriptions was made in 1777 by a physician named Anne-Charles Lorry who gave an account of a man with a very severe and very rare form of ichthyosis.
Ichthyosis vulgaris and X-linked ichthyosis seldom give rise to major problems, and are far more common than one hundred cases per million population. These disorders are therefore not dealt with here.
Lamellar ichthyosis (thick scales) and ichthyosiform erythroderma (finer scales, severely reddened skin) are comprehensive terms for approximately ten variants of the disorder with different causes but similar symptoms. The incidence is 10-20 individuals per million population, which means that there are between 90 and 180 individuals affected by the disorders in Sweden. Every year 2-4 children are born with lamellar or bullous ichthyosis. Bullous ichthyosis (epidermolytic hyperkeratosis) is very rare, affecting only a few individuals per million population.
Ichthyosis is caused by reduced cell desquamation (the process by which cells are shed from the skin), or increased production of cells in the outer layer of the epidermis, the stratum corneum, making it thicker and impairing its normal function. The stratum corneum consists of various structural proteins, moisture-binding substances, and fats that combine to make the skin a barrier between the body and the environment.
The aetiology of the disorder has been determined for some forms of lamellar ichthyosis and ichthyosiform erythroderma, all forms of bullous ichthyosis, Sjögren-Larsson syndrome, and for Netherton syndrome.
In approximately a third of all cases of lamellar ichthyosis (ichthyosiform erythroderma) the skin is deficient in an enzyme called transglutaminase 1. This enzyme is essential for the development of the cornified cell envelope in the horny layer of the skin. The result of reduced or absent enzyme production is disturbed keratinisation and accumulation of defective horn cells on the skin surface. Lamellar ichthyosis can also be caused by lack of ichthyin, a protein which binds fat, or by mutations of certain ALOX genes which encode the production of enzymes that participate in the formation of specialized lipids important for the skin barrier. Mutations of three other genes have recently been found to cause the disorder, among them the ABCA12 gene that encodes a protein needed for transportation of lipids in the skin. A mutation causing total lack of this protein results in an extremely severe form of the disease called harlequin ichthyosis. More research is needed, however, to gain a full understanding of the genetic background of the congenital forms of ichthyosis.
In bullous ichthyosis, the defect is located in one of the keratins (proteins) that form the cellular skeleton of epidermal cells. The anomalous keratin molecules are erroneously built into the cellular skeleton, which becomes fragile, resulting in cellular break-up. Moreover, excessive keratin accumulates in the remaining horny cells, thickening the stratum corneum.
Information about Sjögren-Larsson syndrome and Netherton syndrome is available in the Swedish Rare Disease Database.
Figure. Cross section of skin and enlargement
As a rule, lamellar ichthyosis (ichthyosiform erythroderma) is an autosomal recessive hereditary disorder, although rare autosomal dominant forms of the disease probably exist.
Autosomal recessive inheritance means that two copies of the mutated gene are needed in order to develop the disease. If both parents have only one copy of the mutated gene they are called carriers. Their children will have a 25 per cent risk of inheriting two mutated genes (one from each parent) and developing the disease. In 50 per cent of the cases the child will inherit only one copy of the mutated gene and become a healthy carrier. In 25 per cent of the cases the child will inherit two normal genes and will neither develop the disease nor pass it down.
If one parent is not a carrier, but the other has an inherited autosomal recessive disorder (and thus has two copies of the mutated gene), the children will all be carriers of the mutation but the condition will not affect them. If an individual with an autosomal recessive disorder has a child with a healthy carrier, who has one copy of the mutated gene, there is a 50 per cent risk that the child will develop the condition, while in 50 per cent of the cases the child will be a healthy carrier.
Most cases of bullous ichthyosis are caused by a new mutation, meaning that the mutated gene has not been inherited and is not present in the affected individual’s family. The risk that parents of an affected child will have another child with the disease is therefore virtually non-existent. The new mutation, however, is hereditary and there is a risk that a person with a new mutation passes it down to the next generation. In these cases, the pattern of inheritance is autosomal dominant. This means that only one copy of the mutated gene is needed in order to develop the disease. If one parent has the disease, the risk of passing it down to sons or daughters is 50 per cent. Children who do not inherit the mutated gene will neither develop the disease nor pass it down.
All forms of ichthyosis affect the protective function of the skin, making it dry, thick, scaly, and often red. The symptoms present differently, however, in lamellar and in bullous ichthyosis, as the skin surface in the latter form is sometimes moist rather than dry.
Lamellar ichthyosis
In lamellar ichthyosis, the visible signs of a disturbed keratinisation process vary from fine light scaling to large, often dark-coloured, thick scales covering the whole body. The skin is often extremely dry and sometimes develops superficial cracks. The skin may redden (erythroderma), hair and nails tend to be affected, and there may be extensive scaling and thickening of the skin on the palms of the hands and soles of the feet. The severity of the symptoms varies greatly as does the impact on daily living.
Lamellar ichthyosis manifests at birth when the baby is usually encased in a parchment-like membrane (“collodion baby”). This membrane cracks and is shed in a matter of days or weeks. The severity of the skin disorder can usually be determined during the first few months of life. Approximately 20 per cent of these children have a milder form of ichthyosis, usually caused by ALOX mutations which result in fine scaling and slight dryness. The ability to perspire is usually affected, however. This form of the syndrome is sometimes called “self-healing collodion baby”.
In both children and adults, the eyes do not always close completely and the lids of the eyes may be turned outwards (ectoproion). These individuals often sleep with their eyes slightly open, which may lead to itching, infections, and runny eyes.
If dead skin cells build up in the auditory canals, hearing may be affected.
More than 80 per cent of those with lamellar ichthyosis have trouble maintaining an even body temperature, as there is a disturbance in the dissipation of heat over the horny layer. The ability to perspire is reduced, which can cause individuals with the disorder to be hot, tired, irritable and liable to develop headaches during physical exertion or when the outdoor temperature is high. It is also common to be excessively sensitive to cold. Many individuals with severe ichthyosis find that the condition of their skin becomes worse in extreme heat and cold.
Children with severe ichthyosis may fail to thrive during the first year of life. Weight gain can be slower than expected or even absent for long periods of time.
In severe lamellar ichthyosis the hair may also be affected. Individuals with the disorder often have poor growth of hair or a high hairline, and sometimes the hair grows only in patches or is completely missing.
Children who have an extremely severe form of the disease known as harlequin ichthyosis are born with a massive horny shell of scales covering their bodies. The taut layer of thick skin restricts both growth and movement, leading to protruding mouth and eyes and to abnormalities such as shortened fingers and toes and flattened or absent outer ears. Harlequin ichthyosis is very rare. Only half of the children survive infancy, and later develop severe lamellar ichthyosis with intense redness of the skin and reduced growth.
Bullous ichthyosis
Newborns with bullous ichthyosis have blisters and superficial sores all over their bodies. The blisters heal but tend to flare up at intervals, for instance in conjunction with skin infections.
During infancy the skin thickens and spiny scales appear. Later, the skin becomes excessively thick and scaly especially on knees and elbows and in flexural creases. In such spots, the skin is very brittle, and difficult to keep soft and clean. Thick scales tend to collect in the folds of the skin, which may restrict movement and give rise to an unpleasant odour. Depending on which keratin gene is mutated, the horny layer on the palms of the hands and soles of the feet may also be abnormally thick (a condition known as keratodermia).
The diagnosis is established primarily through clinical examination by a dermatologist and family medical history. Examination of skin samples using light microscopy may be of value, especially in bullous ichthyosis. Electron microscopy and immune staining enable more exact diagnosis, particularly in lamellar ichthyosis. DNA analysis of a blood sample confirms the diagnosis and is necessary if the parents want prenatal diagnosis in the future.
Newborn children with bullous ichthyosis often have blisters and rashes that can be misdiagnosed as epidermolysis bullosa. There is separate information material about this group of disorders in the Swedish Rare Disease Database.
There is currently no cure for any of the ichthyoses, but a great deal can be done to ease the symptoms. Ichthyosis requires continuous treatment, which may be both time-consuming and cosmetically displeasing. In severe cases medications exist which can be helpful, but there is a risk of serious side effects.
Newborn children with lamellar or bullous ichthyosis need to be cared for at a neonatal ward. A dermatologist should be contacted as soon as possible to make the diagnosis and to help parents and staff. An ophthalmologist should also be contacted at an early stage. After delivery the child is usually kept in an incubator and is placed in a cot as soon as its general state of health allows it.
It is important that the parents are encouraged to see and touch their child even though it looks differently than what they had expected. Breast or bottle feeding the child while holding it is a good way of creating a bond between parents and child.
As the child grows older it becomes important to inform, for example, teachers as well as classmates and others who meet the child about the cause of the skin disorder. It should be emphasised that the disease is not communicable. The fact that the child’s skin is different may cause peers to avoid games that involve holding hands or other kinds of touching. The information given should be suitably adapted to the age of the children, and include explanations of the cause of the disease, its treatment, and the fact that it is not contagious. Information is important to counteract isolation and the development of social problems. Individuals with ichthyosis and their families should be offered professional psychological and social support.
Thick scales in the folds of the skin may restrict movement, in which case physiotherapy may be helpful.
Children who fail to thrive need contact with a dietician, who can monitor the child’s nutrition and recommend supplements if necessary.
Individuals with ichthyosis should take daily baths or showers and keep their skin well moisturised. Ointments and creams with a keratolytic effect should be applied at least once a day. Keratolytic ingredients re-hydrate the skin and work as a peeling agent to shed the horny outer layer. This eases the scaling process, softens the skin, and alleviates any tendencies to cracking. Substances often used include urea, propylene glycol, and some alpha-hydroxy acids, for example lactic acid and glycolic acid. Topical salicylic acid may be used on small skin areas.
Long baths at least once a week are a vital part of the treatment regime. Oil, salt or urea should be added to the bathwater to soften the skin. The scales can then be removed using a wet washcloth or a pumice stone.
Regular foot care is recommended, for example to alleviate problems with cracks in calloused feet.
Oral retinoids (derivatives of vitamin A) are sometimes used. These have a normalising effect on the keratinisation process, but treatment results vary among the different types of ichthyoses. Owing to the risk of foetal malformations, pregnant women must not be treated with retinoids, and the treatment must be stopped well in advance of a planned pregnancy, as the secretion of retinoids is very slow. The liver, the skeleton, and blood lipids may also be affected by long-term treatment.
In the choice of career, it is advisable for individuals with ichthyosis to avoid professions that require being in very dirty, hot, or extremely cold environments.
Lamellar ichthysosis
Newborn children with lamellar ichthyosis need to be treated 6-8 times a day with a cream consisting of equal parts paraffin and petroleum jelly. Medical staff should check regularly that the skin is not infected, since infected skin cracks may lead to blood poisoning (septicaemia).
The thick membrane, collodion, with which many of the children are born, cracks and is shed within the first few weeks. The membrane can be shed earlier if the child is given frequent baths as soon as the umbilicus has healed. Ordinary tap water can be used.
Newborns who lack the collodion membrane are sometimes born with an intense redness of the skin. As the skin barrier is thin and damaged, these children lose a great deal of heat and moisture through the skin. The fluid balance needs to be carefully monitored. Ointments used to lubricate the skin must also be chosen with care, since foreign substances can easily penetrate the thin skin barrier.
Scales on the scalp may be removed with a fine-toothed comb after the scalp has been treated with ointment for a few hours, or after being lubricated and then covered with a cap or some plastic during night.
If a person with ichthyosis has trouble closing his or her eyes properly, an ophthalmologist should be consulted. Eye drops or lubricants (tear substitutes) need to be used daily to prevent dehydration and permanent damage to the cornea. In some cases, eyelid plastic surgery may be helpful.
If hearing is affected owing to accumulation of dead skin cells in the auditory canals, an ear specialist may help remove the loose skin.
As most individuals with lamellar ichthyosis are sensitive to heat, it is crucial to avoid overheating. An air-conditioned car may be very helpful for travelling in hot weather. A spray bottle of water, a plastic bag of ice cubes, or a wet towel from a cooler bag are helpful aids in hot weather. It is important to inform preschool and school personnel about the disease, especially as the child needs extra attention when playing or participating in games or sports.
Bullous ichthyosis
Topical retinoids (A-vitamin derivatives) are sometimes effective in the treatment of bullous ichthyosis.
In order to avoid damaging the skin the child should not be monitored with electrodes taped to the body, or other adherent materials. Non-adherent dressings should be applied to sores and blisters.
Bacterial infections may lead to increased blistering and should be treated with antibiotics. If there is a problem with recurring skin infections, prophylactic antibiotics may be necessary.
The home should be easy to keep clean (and have no wall-to-wall carpeting). A good vacuum cleaner is necessary to remove the large amounts of peeled skin that may accumulate on the floor. If possible, there should be a tub in the bathroom and room enough to apply moisturisers. It is also practical to have a large cupboard for storage of various treatment items.
Washing machines should contain as few rubber gaskets as possible, as the ointments erode them. Water use and laundry detergent consumption will be extremely high.
Clothing should be cotton, which is preferable to synthetics. Underwear and socks and stockings, as well as sheets and bath towels, tend to be subject to hard wear.
The diagnosis is established at a county hospital dermatology clinic. Severe cases may be referred to the dermatology clinic at Uppsala University Hospital, the national centre of expertise for certain types of inherited dermatologic disorders (genodermatoses). After the diagnosis has been confirmed, treatment is managed by a dermatologist and a paediatrician.
Professor Anders Vahlquist, Dermatology Clinic, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. Tel +46 18 611 30 00, fax +46 18 611 26 80, email: anders.vahlquist@medsci.uu.se.
Agneta Gånemo, RN, PhD, Dermatology Clinic, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. Tel +46 18 611 26 78. Or: Gånarpsvägen 335, SE-266 92 Munka Ljungby, Sweden. Tel and fax +46 431 283 80, email: agneta@ganemo.se.
Senior physician Maritta Hellström Pigg, PhD, Department of Clinical Genetics, The Rudbeck Laboratory, Uppsala University Children’s Hospital, SE-751 85 Uppsala, Sweden. Tel +46 18 611 30 00, fax +46 18 611 59 47, email: maritta.hellstrom.pigg@akademiska.se.
The Ichthyosis Association arranges an annual weekend seminar for people with ichthyosis and members of their families. The programme includes lectures, opportunities to exchange experiences, and the annual meeting of the association. The association also arranges regional meetings two or three times every year. For further information, contact the Ichthyosis Association (the address is listed under “Organizations for the disabled/patient associations”).
The Ågrenska Centre arranges stays for children and young people with disabilities and their families, and is particularly attentive to the needs of people with rare diseases. The Centre is located on the outskirts of Gothenburg, and is open to families from all over Sweden. For information, please contact the Ågrenska Centre, Box 2058, SE-436 02 Hovås, Sweden. Tel +46 31 750 91 00, fax +46 31 91 19 79, email: agrenska@agrenska.se, Internet: www.agrenska.se.
The Ichthyosis Association is divided into 12 regions, each with its own liaison officer. Information about the regions and about local contact persons is found on their website. The newsletter of the Ichthyosis Association is published three times per year. Street address: Sturegatan 4 C, Sundbyberg. Mailing address: Box 1386, SE-172 27 Sundbyberg, Sweden. Tel +46 8 546 404 51, Internet: www.iktyos.se.
The Swedish Association for Rare Disorders. Visiting address: Sturegatan 4A, Sundbyberg. Mailing address: Box 1386, SE-172 27 Sundbyberg, Sweden. Tel +46 8 764 49 99, email: info@sallsyntadiagnoser.se, Internet: www.sallsyntadiagnoser.nu. The Swedish Association for Rare Disorders is a national umbrella organisation for rare disorder associations. The aim of the association is to promote shared interests of people with rare disorders.
LeLectures on caregiving, treatment and research in the area of ichthyosis are arranged for all categories of personnel, and are held by Agneta Gånemo, RN, PhD (see under “Resource personnel”).
Several research projects on the ichthyoses are carried out at Uppsala University Hospital and at Uppsala University.
- Basic research on the keratinisation mechanisms, retinoid treatment and genetic molecular characterisation of congenital ichthyoses. Contact person: Professor Anders Vahlquist, Dermatology Clinic.
- New treatments. Contact persons: Marie Virtanen, MD, PhD, and Professor Anders Vahlquist.
- Caregiving and quality of life in ichthyosis. Contact person: Agneta Gånemo, RN, PhD.
- Molecular genetic characterisation of congenital ichthyoses. Contact persons: Professor Niklas Dahl and Maritta Hellström Pigg, MD, PhD, Department of Clinical Genetics, The Rudbeck Laboratory.
Short summaries of all the information texts in the Rare Disease Database of the National Board of Health and Welfare are available as leaflets, in Swedish only. They can be printed out or ordered by selecting the Swedish version of each text, and then clicking on the leaflet icon which will appear under “Mer hos oss” in the column on the right-hand side.
Information material from the Ichthyosis Association (the address is listed under “Organizations for the disabled/patient associations”):
- “Iktyos – en handbok för dig som vill veta mer” (in Swedish only). Handbook about Ichthyosis by Agneta Gånemo. Ängelholm 2008. ISBN 978-91-633-3327-9.
- “Att leva med iktyos” (in Swedish only). Information DVD about living with ichthyosis. The Ichthyosis Association also provides booklets and folders that can be ordered free of charge, or downloaded from their website: www.iktyos.nu.
There is a newsletter from the Ågrenska Centre (in Swedish only), no. 222 (2003). Order from: Ågrenska, Box 2058, SE-436 02 Hovås, Sweden. Tel +46 31 750 91 00, fax +46 31 91 19 79, email: agrenska@agrenska.se. The newsletter can also be downloaded from their website: www.agrenska.se.
Dahlqvist J, Klar J, Hausser I, Anton-Lamprecht I, Pigg MH, Gedde-Dahl T et al. Congenital ichthyosis: mutations in ichthyin are associated with specific structural abnormalities in the granular layer of epidermis. J Med Genet 2007; 44: 615-20.
DiGiovanna JJ, Robinson-Bostom L. Ichthyosis: etiology, diagnosis, and management. Am J Clin Dermato. 2003; 4: 81-95.
Fowler AJ, Moskowitz DG, Wong A, Cohen SP, Williams ML, Heyman MB. Nutritional status and gastrointestinal structure and function in children with ichthyosis and growth failure. J Pediatr Gastroenterol Nutr 2004; 38: 164-169.
Gånemo A, Lindholm C, Lindberg M, Sjödén PO, Vahlquist A. Quality of life in adults with congenital ichthyosis. J Adv Nurs 2003; 44: 412-419.
Gånemo A, Pigg M, Virtanen M, Kukk T, Raudsepp H, Rossman-Ringdahl I et al. Autosomal recessive congenital ichthyosis in Sweden and Estonia: clinical, genetic and ultrastructural findings in eighty-three patients. Acta Derm Venereol 2003; 83: 24-30.
Gånemo A. Iktyos - en handbok för dig som vill veta mer! Ängelholm 2008. ISBN 978-91-633-3327-9.
Oji V, Traupe H. Ichthyoses: Differential diagnosis and molecular genetics. Eur J Dermatol 2006; 16: 349-359.
Traupe H. The ichthyosis. A guide to clinical diagnosis, genetic councelling and therapy. Springer Verlag, Berlin, 1989.
Vahlquist A, Gånemo A, Virtanen M. Congenital ichthyosis: an overview of current and emerging therapies. Acta Derm Venereol 2008; 88: 4-14.
Vahlquist A, Ganemo A, Pigg M, Virtanen M, Westermark P. The clinical spectrum of congenital ichthyosis in Sweden: a review of 127 cases. Acta Derm Venereol 2003; 213: 34-47.
Vahlquist A, Rollman O. Kutan genterapi-potentiell behandling för svåra hudsjukdomar. Läkartidningen 2002; 99: 2041-2045.
OMIM (Online Mendelian Inheritance in Man)
Internet: http://www.ncbi.nlm.nih.gov/omim
Search: ichthyosis
GeneReviews (University of Washington)
Internet: www.genetests.org (select Genereviews)
Search: ichthyosis
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. Agneta Gånemo, RN, PhD, also contributed to updating the information.
The relevant organizations 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: 2009-06-24
Version: 4.1
Publication date of the original Swedish version: 2009-04-06
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.