Neurofibromatosis, neurofibroma: pictures, types, treatment, symptoms
Neurofibroma is a tumor of the nerve, which includes the whole complex of cellular elements, including fat, Schwann cells, fibroblasts. Neurofibromatosis (NF) is called the disease of Recklinghausen named who first described her doctor in the late 19th century. Being the most frequent hereditary disease in the General population neurofibromatosis is relatively rare. The first type of NF is diagnosed in one newborn from 3500-4000, the second type is more rare – in the one case in 50,000 children.
The disease is more often diagnosed in men, and its first signs become apparent in childhood and adolescence. Given the genetic nature of the pathology, manifestations of neoplastic lesions arise in childhood or even visible at birth, although in many cases hidden symptoms allows diagnosis at an early stage.
Neurofibromatosis are among the most enigmatic tumors. Possible cytogenetic method has allowed to establish the presence of a mutation in a specific gene, but it is still unclear why in this case a tumor develops, what are the mechanisms and provocateurs of the disease. The more important and unresolved issue is the treatment, which today can only reduce the symptoms of the disease and little to restrain its progression.
Causes and types of neurofibromatosis
The causes of the disease Recklinghausen is unknown, but the main pathogenetic link believe genetic defect in chromosome 17 in the first type of NF and 22 – in the second. Pathology is inherited in an autosomal dominant way, this means that anyone with the gene will be ill, asymptomatic carriers of the impossible. If one parent has the disease Recklinghausen, the probability of having a child with disease is 50%. If both parents patients this figure increases up to 66.7%.
Due to the hereditary mechanisms of pathogenesis, the disease runs in families and among relatives of the sick will be those who are already suffering from disease. In rare cases NF develops in healthy families because of spontaneous single mutation.
Studies of the genetic factor suggests that the genes in which mutation appears, normally have antioncogene action. In the pathology reduced or completely stops the production of their protein neurofibromin, which is responsible for proper differentiation and proliferation of cells in the nerve endings. In the absence of this protein starts an uncontrolled proliferation of cellular elements, and it applies not only Schwann cells that wrap processes of neurons, but also fibroblasts, mast cells, lymphocytes. At the same time changing the composition of the intercellular substance in the tumor submitted to acidic mucopolysaccharides.
Localization neurofibroma decided to allocate several forms of pathology:
- Neurofibromatosis type 1, when the neoplastic process affects the peripheral nerves, it is more common type of NF;
- NF type 2 with involvement of the Central nervous system (CNS), is much rarer;
- NF 3 is a very rare variety and is accompanied by a lesion of the palms, the auditory nerve, tumors of the brain;
- NF 4 types are very rare, the symptoms are the same as in the first type, but the nodules lisha do not exist.
In type 1 Recklinghausen disease affects the peripheral nerves, the skin appear characteristic spots and pigmentation disorders, the process usually is common, affects the optic nerve, the iris, perhaps combined with bone defects. In NF type 1 usually known and relatives suffering or who suffered from this disease.
Neurofibromatosis type 2, more rare, is accompanied by damage to the auditory and optic nerves, usually of a bilateral nature, the formation of tumors in the brain, while cutaneous manifestations may be expressed not too much.
Neurofibromatosis in children is also caused by genetic mechanisms, and a sick child the symptoms appear quite early. Usually, the manifestation of the pathology between the ages of 3-15 years, especially high risk of progression is noted during periods of rapid child growth, when all cells multiply intensively, actively go biochemical metabolic processes, which creates prerequisites for the growth of the tumor including.
The main signs of the disease in children do not differ from those in adults, but have some peculiarities. Marvel at the peripheral, optic and auditory nerves, skin and internal organs. The presence of a large tumor disrupts the growth of the child, appear deformation of the limbs, curvature of the spine, slows the development of intelligence, there is a tendency to severe depression. Developmental disorders of the locomotor apparatus is very typical for NF childhood, because the adult skeleton is already formed, and the tumor may not have such influence on bone.
Symptoms of the disease Recklinghausen
For NF is a very diverse clinical picture, the defeat of many organs besides the skin, progressive course. Possible complications, including the deadly malignant transformation, failure of the heart, lungs, CNS.
Symptoms do not appear immediately, but successively at different ages, so suspect NF in young children is problematic. The only sign of pathology in the first years of life can be dark spots, while other symptoms appear later, between 5 and 15 years.
NF may provoke external constraints and stressful conditions such as:
- Adolescence and hormonal changes associated with it;
- Pregnancy and childbirth;
- Acute infection and pathology of internal organs.
The progression of the disease can be caused by medical manipulation, massage, physiotherapy, removal of small neurofibroma cosmetics. It is now widely accepted to assign to massage babies first year of life, Recalling the possible pathology of locomotor apparatus, but in this period the most difficult to diagnose NF, signs of which may not be available, so the doctors dealing with young children should consider this possibility and at least find out from parents if there are unfavorable heredity in relation to disease of Recklinghausen.
For NF is very different in different patients. It is impossible to predict exactly at what age and what kind of symptoms will appear. Than due to large differences in clinical disease, is still unclear.
The main symptoms of neurofibromatosis consider:
- Age spots;
- Tumor masses of the peripheral nerves, located subcutaneously;
- Violation of lymphatic drainage;
- The defeat of the auditory, optic nerve;
- Skeletal anomalies.
Age spots is one of the most typical and early symptoms of neurofibromatosis. They are located on the skin of the trunk, neck, rarely on the face, hands and feet. Their diameter exceeds half an inch, so to see them in the newborn is not too difficult. The color of the spots it is light yellow to brown, although they can be blue-purple hue.
Peripheral tumors of nerves found under the skin in the torso area, neck, head and limbs, multiple, and sometimes their number is beyond counting. These neuromas are a significant cosmetic defect them by mutilating the surface of the body and face. Often, even in the presence of internal lesions or brain is a cosmetic defect becomes the main complaint of the patient.
Peripheral neuroma consists of Schwann, mast cells, lymphocytes and connective tissue component, it is dense, often painless and easily movable when feeling. Possible pain and itching at the site of growth of the neoplasia. The size an average of about two centimeters, but there are large neurofibromas up to several kilograms in weight. The skin covering neurofibroma, sometimes pigmented.
Neurofibromas can compress the nerve trunks and blood vessels, resulting in pain and impaired lymphatic drainage. Patients note increase in size of the limbs, tongue, face, other body part that is connected with stagnation of lymph. Compression of the mediastinum leads to shortness of breath, difficulty breathing, cardiac arrhythmias, congestive heart failure.
Plexiform neurofibroma may be diffuse, be placed on a broad basis or to hang above the surface of the skin, usually it is soft consistence, is formed under the skin or in internal organs. These tumors can cause excessive growth of the skin and tissue, forming a large hanging nodes, covered with pigmented wrinkled skin. In the depths of such a conglomerate is possible to probe the tangle of thickened nerves. Plexiform neurofibromas in the head, face, torso, disfigured, and when inside the body compress the organs, impairing their function.
Neurofibromatosis type I may be accompanied by abnormalities of the skeleton, the curvature of the spine and disruption of the formation of the vertebrae, asymmetrical skull. The characteristic feature of this type of disease is a knot lisha – whitish spot on the iris of the eye, which has more than 90% of patients.
The CNS is accompanied by nerve tissue tumors (gliomas, meningiomas), to compress her spinal roots, cranial nerves. Patients with such changes complain of headache, mood lability, and the neurologist detects a violation of the sensitivity of sphere, disorders of coordination, speech. Neuroma of the optic or auditory nerve dangerous vision disorder, glaucoma, deafness.
In children, brain damage inevitably leads to delayed mental and intellectual development. Young patients are extremely prone to severe depressions, which are very very difficult to treat. Major intracranial neurofibromas can cause convulsions.
For the diagnosis of NF doctor about cutaneous manifestations, the presence of peripheral tumor-like formations, finds out the family history. Group of experts on the neurofibromatosis were allocated to the signs that must be surveyed to confirm neurofibromatosis, and identify at least 2 of them can reliably judge the development of the disease:
- 5 or more spots of light coffee color with a diameter of more than 0.5 cm before puberty;
- 6 or more spots half an inch in size after puberty;
- A minimum of 2 nodules at the iris;
- Multiple small pigment spots in the skin folds;
- At least 2 of any neurofibroma or 1 plexiform;
- Glioma of the optic nerve;
- Changes of bone – dysplasia-wing of the main bones of the skull, congenital thinning of the cortical layer of tubular bones;
- The presence among the relatives of patients with neurofibromatosis.
Diagnosis and treatment
Because the earliest sign of NF are age spots, then the first doctor they may face – a dermatologist. If after inspection and conversations with the patient or his parents will be in the expectation of neurofibromatosis, then you will need further investigation – CT, MRI of brain, spine.
Mandatory the patient is directed to consult a ENT doctor for the study of the organ of hearing, and to an ophthalmologist to exclude optic nerve damage. In some cases, participate in the diagnosis of the orthopedist, the neurologist, the neurosurgeon.
The issue of the treatment of neurofibromatosis remains open. Still not really developed effective methods of dealing with the tumor, therefore, symptomatic therapy is the only thing that can help the doctors to such patients.
In relation to benign neurofibroma not effective anticancer drugs, but they can be assigned during the malignant transformation of tumors. Radiation therapy does not make sense when multiple lesions because the radiation dose is gigantic, and the effect is questionable. With a single malignant neurofibroma irradiation is performed.
Surgical treatment is the main way of combating many tumors, but not in the case of neurofibromatosis. First, a common tumor process to remove it is not possible technically, and secondly- often the removal of neurofibroma provokes progression of the disease and the appearance of new tumors. On the other hand, a cosmetic defect makes the surgeon go for this treatment.
When a large plexiform neurofibroma, localized in the internal organs, near the neuro-vascular bundles and important structures of the body surgical treatment is aimed at resolving the compression of the bodies and is done for health reasons. For example, when neurofibroma mediastinum that disrupt breathing, cause arrhythmia, impaired blood flow surgical treatment is justified.
Symptomatic therapy is the main way of dealing with neurofibromatosis. It allows you to keep the progression of disease, reduces painful symptoms and itching. Patients are analgesics, anti-inflammatory, antihistamines.
Russian scientists after years of observation and research have developed a scheme of pathogenetic conservative treatment of neurofibromatosis type I, which has been quite effective. It includes drugs acting on metabolic processes and the activity of the cells that comprise the tumor.
To prevent degranulation of mast cells and stabilization of their membranes is assigned to ketotifen for a short period of 2 months, in doses up to 4 mg per day. Concurrent use of antihistamines fenkarol avoids some of the adverse reactions ketotifen. Fenkarol is shown in the first two weeks of starting treatment.
Reduction of proliferation (reproduction) of cells in the growth of neurofibromas can be achieved by use of the drug tigazon, which is synthesized on the basis of vitamin A. In the absence of aevitum appointed. Drugs retinoids have a lot of serious side effects, including teratogenic effects, so their use in Pediatrics, pregnant women should be limited or eliminated completely.
With an absorbing target is used lidaza up to 64 units based on the age of the patient, it is administered intramuscularly, every other day, in the course of assigned 30 shots.
These drugs are recommended comprehensively or as monotherapy, depending on the age, sex, form of the disease and specific symptoms. The next course of treatment is mandatory when signs of progression of neurofibromatosis, and to all the situations that can trigger the growth of tumors – surgery, birth. For large neurofibroma located inside the body, severe pain tumors can be assigned to repeated courses in 2 months.
The result of treatment by the proposed scheme is the reduction in the growth of neurofibroma, slowing the progression of the disease. In some cases, doctors have observed shrinkage of individual tumors and even their complete disappearance, especially at the beginning of therapy at an early stage.
The described scheme is quite well tolerated by many patients, and changes of biochemical parameters of blood and allergic reactions were rare, therefore, domestic experts recommend a combination of these medications for widespread use, because it really helps in the fight against incurable serious illness.
The search for an effective treatment for neurofibromas continues. Annually in developed countries for the solution of this problem are allocated huge funds, and the efforts of scientists aimed at the development of etiotropic treatment. It is known that the reason is genetic disorders, so genetic engineering techniques can help to find a way of dealing with NF. Active research in this direction started in the late last century and I want to believe that the result will be positive, and the disease will become, if not fully curable, it is controlled.
The prognosis for life with neurofibromatosis quite favorable, most patients retain the ability to work. The risk of malignant transformation of the neuromas, as well as large plexiform of the tumor, compressing the organs, vessels, nerves, and Central pathology form.