Congenital pachionychia is a heterogeneous group of genetic pathologies having the character of ecto– and mesodermal dysplasia with different types of inheritance. Symptoms of this disease are thickening and subsequent dystrophy of the nails on the hands and feet, keratodermia, especially on the feet, plantar pain, warty growths and peeling of the skin. Diagnosis of congenital pachionychia is performed by examining the skin, as well as by genetic analysis – for forms in respect of which key genes have been identified. There is no specific treatment, symptomatic and supportive therapy with vitamin preparations, treatment of keratinized skin and nails are used.
Congenital pachionychia (Jadasson-Levandowski syndrome, congenital polyceratosis) is a heterogeneous group of hereditary genodermatoses that are characterized by disorders of the keratinization processes of some areas of the skin and nails. The disease was first described in 1906 jointly by two German dermatologists – Josef Jadasson and Felix Lewandowski, who also proved its familial nature. To date, it is known that congenital pachionychia is a whole group of pathologies with different inheritance patterns: autosomal recessive, autosomal dominant and gender-linked. Because of this, it is quite problematic to derive some averaged statistical data on the sexual distribution and occurrence of pathology. According to the latest data, men predominate among patients with congenital pachionychia, the sex ratio is approximately 7:4. The disease is very variable in its symptoms and manifestations, even within the same family form, the clinical picture may vary significantly among relatives.
For a long time, the etiology and pathogenesis of congenital pachionychia were little known, and even today genetics and dermatology explain the development of only some forms of this condition. So, in relation to the pathogenesis of the type of disease that is transmitted by a sex-linked mechanism, there are not even more or less recognized theories. The most studied forms of congenital pachionychia are associated with a violation in the genes of four types of keratins. More often it is the KRT16 gene located on the 17th chromosome and encoding the sequence of the keratin-16 protein, and the KRT6A gene localized on the 12th chromosome and responsible for the keratin-6A protein. Rarer forms of congenital pachionychia are caused by mutations in the genes KRT17 and KRT6B (17th and 12th chromosomes), which respectively encode keratins of types 17 and 6B. A great influence on the clinical course and the mechanism of inheritance of the disease is not only what gene has undergone mutation, but also the nature of this defect.
In the structure of the skin, almost all types of keratins are divided into peculiar pairs that combine to form dimers with an alpha-helical structure – this is the first stage in the formation of more complex polymers. The above proteins are no exception – the “pair” for keratin type 16 is type 6A, and for keratin-17 is type 6B. Disturbances in the structure of one of the components of the pair lead to difficulty in forming a normal connection between them and are the cause of the symptoms of congenital pachionychia. It is these varieties of keratins that are most represented in nails, hair, and skin on soles, which explains this clinical picture of the disease. For other forms of congenital pachionychia, the connection of which with keratins has not been proven, other pathogenesis mechanisms are assumed – among them, a violation of the absorption of certain vitamins, insufficiency or, conversely, excessive activity of certain skin enzymes and a number of other theories.
The modern classification of congenital pachionychia includes only those forms of the disease whose pathogenesis is known and which, depending on the nature of the mutation, are transmitted by autosomal dominant or autosomal recessive mechanisms. Rare varieties of pathology linked to sex have not been classified to date, as well as those for which the genes responsible for them have not yet been found. Initially, the known types of congenital pachionychia are divided into two types – the Yadasson-Levandovsky type (caused by impaired connections in a pair of keratins 16-6A) and the Jackson-Lawler type, the cause of which lies in defects in the structure of keratins 17-6B. Then they are divided into four subtypes, which, in addition to various etiologies, also have their own features of the clinical course:
- Subtype 1 is caused by a mutation of the KRT16 gene, therefore, it belongs to the Yadasson-Lewandowski type. It is the most classic and characteristic type of congenital pachionychia, considered by some researchers as a kind of standard of this disease.
- Subtype 2 – caused by mutations of the KRT17 gene, belongs to the Jackson-Lawler type. It is less common than the first subtype and differs from it by anomalies of tooth formation – in almost half of cases of such congenital pachionychia, patients have their intrauterine or neonatal development.
- Subtype 3 is an even rarer form of this pathology, due to defects in the structure of the KRT6A gene, belongs to the Yadasson-Levandovsky type. This type of congenital pachionychia is most characterized by autosomal dominant inheritance, in addition, it is accompanied by eye damage – cataract, corneal dyskeratosis – and disorders of the mucous membrane of the mouth and lips (angular cheilitis).
- Subtype 4 is the rarest classified form of this disease, caused by mutations of the KRT6B gene, belongs to the Jackson-Lawler type. In addition to the manifestations characteristic of congenital pachionychia, it is also characterized by the development of mental retardation, alopecia, hoarseness of voice.
All types of congenital pachionychia are characterized by a certain set of standard symptoms, the main of which is a change in the nail plates, which is determined already in the first weeks and months of a child’s life. The nails on the hands and feet thicken, sometimes reaching 1 centimeter, their density increases, they lose their natural shine and acquire a dull yellow hue. Also, congenital pachionychia is characterized by the presence of dark longitudinal stripes on the nails and their deformation (sometimes by the type of “watch glasses”), the skin under them undergoes severe hyperkeratosis. In rare cases, such manifestations serve as almost the only symptom of this disease.
In other cases, several months or years after the appearance of the first signs of congenital pachionychia, hyperkeratosis zones appear on the feet, which are localized in areas subjected to pressure. These foci have the appearance of large calluses, are often quite painful, bubbles and cracks may appear on their surface, which sometimes become infected, complicating the course of the disease. In the future, similar areas of hyperkeratosis appear on the feet, extensor surfaces of the joints, follicular keratosis occurs on the skin in the form of small, acne-like papules. On the buttocks and knees, the formation of warty growths is possible, in some places skin peeling may occur, resembling ichthyosis. A characteristic sign of congenital pachionychia is also the development of foot or palmar hyperhidrosis.
The above symptoms are a kind of “standard” of the disease, since they occur in almost any form of it. At the same time, each subtype of congenital pachionychia is characterized by additional clinical manifestations, which sometimes allow specialists to determine it without the help of a geneticist and molecular diagnostics. So, for subtype 1, a characteristic symptom is the development of leukoplakia on the oral mucosa. According to some data, in the long term, these foci can cause the development of malignant neoplasms (cancer of the tongue, lower lip). Congenital pachionychia subtype 2 is characterized by abnormal development of teeth, which sometimes grow in utero or in the first weeks of an infant’s life. At the same time, their structure is broken, they are small in size and quite often fall out within a few years.
Subtype 3 of congenital pachionychia can be determined by a combination of lesions of the mucous membrane of the oral cavity and the organs of vision. They are reduced to the development of angular cheilitis and leukoplakia, similar to those in the disease of subtype 1. Ocular manifestations are represented by the frequent development of cataracts and corneal dyskeratosis, which leads to visual impairment at an early age. Congenital pachionychia of subtype 4 is considered the rarest, but at the same time, the most severe form of this disease, as it often combines the symptoms of the previous three types and additionally leads to mental retardation, hoarseness of voice, disruption of the structure and growth of hair up to focal or total alopecia.
Congenital pachionychia is characterized by high variability of symptoms, even within the same family line (due to the same mutation), the clinical picture of the disease can vary significantly. The mechanisms of this are unknown, the influence of factors such as the reactivity of the body, the activity of the immune system and a number of others is assumed. In addition, in some cases, congenital pachionychia can be combined with signs of mesodermal dysplasia – Gothic palate, spina bifida, changes in the shape of the skull, malformations of bones. It is unclear whether this disease is the cause of such disorders or is caused by a simple combination of various anomalies of embryogenesis.
The determination of congenital pachionychia is made on the basis of the data of the patient’s current status and genetic studies, sometimes a biochemical analysis of urine is additionally investigated. In the latter, a high content of hydroxyproline is determined, the reasons for this are unknown – perhaps due to a violation of the formation of macromolecules of the skin. Examination reveals a significant thickening of the nails, possible paronychia, the development of hyperkeratosis of the feet and other skin areas, increased sweating of the palms. Patients with congenital pachionychia complain of sharp plantar soreness when walking, pain in the fingers with the development of paronychia. Depending on the subtype of the disease, other symptoms can be determined – prenatal teeth, oral leukoplakia, ocular disorders, mental retardation and mesodermal dysplasia.
The study of the hereditary history of a patient with congenital pachionychia in some cases confirms the family nature of the disease, and the mechanism of its inheritance may be different. Modern genetic diagnostics most often uses the method of direct sequencing of the KRT6A and KRT6B gene sequences in order to search for mutations, only a few laboratories perform a similar procedure for the KRT16 and KRT17 genes. For other forms of congenital pachionychia, which are caused by the defeat of other genes, methods of genetic diagnosis have not been developed to date.
In some cases, a skin biopsy is performed in the areas of lesions for the purpose of its histological examination. When examining tissues under a microscope, pronounced hyperkeratosis, thickening of the epidermis is determined, there are signs of acanthosis, sometimes there may be inflammatory manifestations and lymphocytic infiltration. The latter increases with infection of cracks, blisters or other skin formations that occur due to congenital pachionychia. Differential diagnosis of this disease should be carried out with congenital ichthyosis, some other forms of keratosis (including acquired ones), idiopathic onychogryphosis.
Specific treatment of congenital pachionychia has not been developed, symptomatic and supportive therapy is used. To reduce the thickness and degree of deformation of nails, a variety of cosmetic nail files and rasps are used, specialized electric tools of this kind have a good effect. Local remedies based on moisturizers (glycerin, urea) and organic acids can facilitate the removal of excess thickness of nails and areas of plantar hyperkeratosis. The use of non-narcotic analgesics from the NSAID group (ibuprofen, nimesulide) can reduce pain when walking or other actions.
Of the other drugs used to treat congenital pachionychia, various forms of retinoids are most often used. Systematic use of significant doses of such drugs inside can significantly reduce the severity of hyperkeratosis, however, it is fraught with side effects, therefore the scope of their application is limited. Locally, with congenital pachionychia, soda 10% baths, salicylic and corticosteroid ointments, local forms of retinoids are used. Areas of hyperkeratosis can also be removed by electrocoagulation or cryodestruction. In some cases, it is necessary to resort to surgical treatment – removal of deformed nails and skin cysts.
Prognosis and prevention
The prognosis of congenital pachionychia relative to the patient’s life is most often favorable if it is not accompanied by severe mesodermal dysplasia. However, it is almost never possible to achieve recovery or stable remission of the disease. Palliative care can be used to reduce the severity of symptoms. Plantar hyperkeratosis and soreness can reduce the use of special orthopedic shoes that evenly distribute the load over the entire surface of the foot. With the development of leukoplakia on the mucous membranes of the oral cavity, it is important to regularly be examined by a dermatologist or oncologist – there is a certain risk of developing a malignant neoplasm. Otherwise, congenital pachionychia, although it worsens the quality of life of the patient, is not a life-threatening condition.