Cutaneous amyloidosis is a consequence of a chronic pathological process in which amyloid is deposited in the skin in the form of rounded or pointed foci – an insoluble compound of fibrillar protein and polysaccharide, which is unusual for the body in normal conditions. Deposits have the appearance of papules, nodules, plaques of a solid, brownish or bluish hue. The diagnosis is based on the detection of amyloid in tissue samples obtained by biopsy. Treatment is aimed at eliminating the causes that caused the development of the disease, normalizing the state of internal organs, eliminating local symptoms of skin lesions.
The outdated name of amyloidosis, which is found in the medical literature, is “sebaceous disease”. The term “amyloid” was first introduced by the German researcher Rudolf Virchow. He suggested that the contents of the plaques of the skin of patients with chronic sluggish infectious diseases is starch. Later it was found that complex carbohydrates make up only a small part of the amyloid molecule, but the term has already taken root in the scientific literature. According to statistics, 1% of the world’s population suffers from amyloidosis. Pathology is diagnosed mainly in men over 40 years of age. Skin lesion in systemic amyloidosis is observed in every second patient. There are about a hundred cases of primary local cutaneous amyloidosis in the world, of which 7 are family.
The accumulation of pathological glycoprotein amyloid is a consequence of a violation of protein metabolism in the body. The cause of protein metabolism disorders determines the type of amyloid, the nature of the course of the disease, clinical manifestations, prognosis for recovery or stabilization of the patient’s condition. Cutaneous amyloidosis may be a consequence of the following pathological processes:
- Chronic inflammation. This group includes rheumatoid arthritis and other inflammatory diseases of the joints, osteomyelitis, bronchiectasis, tuberculosis, leprosy. For localized cutaneous (lichenoid) amyloidosis, some dermatological problems are important: eczema, seborrheic dermatitis, warts, lichen, benign neoplasms, neurodermatitis.
- Plasmocellular dyscrasia. Plasmocytes are normally part of the immune system. The mutation leads to a complete restructuring of the function of these cells. They begin to synthesize abnormal light chains of immunoglobulins. These protein molecules become precursors of AL-amyloid. This is how primary amyloidosis develops.
- Genetic disorders. A number of hereditary varieties of amyloidosis with geographical reference are described: “English”, “Portuguese”, “American”, which have characteristic skin manifestations. This also includes cases of isolated cutaneous amyloidosis in people over 70 years of age who do not have a history of diseases, the complication of which could be amyloid dystrophy.
- Chronic renal failure. With CRF, protein metabolism is disrupted. Beta-2-microglobulin, the precursor of amyloid, accumulates in the tissues. This protein is not delayed by all dialyzers. The detection of amyloid dystrophy in patients on hemodialysis requires the attention of doctors, the selection of more appropriate methods of blood purification.
Currently, a large number of chemical processes leading to the synthesis of various forms of amyloid have been described. Common to all these reactions is an increase in the concentration of proteins in the blood-precursors of amyloid fibrils. Each form of amyloid has its own precursor proteins, each of which differs in the degree of amyloidogenicity. The precursors include transthyretin, B-protein, beta-2-microglobulin, islet amyloid polypeptide and some other proteins. The degree of amyloidogenicity is determined by the presence of changes in the structure of the protein, which may result from genetic disorders or the effects of damaging physical and chemical factors on the molecule.
Glycoproteins are actively excreted by the kidneys, but the rate of excretion is insufficient to purify the blood plasma from pathological compounds. They begin to be deposited in the walls of blood vessels, in the intercellular space of the parenchyma of organs. Accumulations of amyloid disrupt the vital activity of cells, lead to compression of nerves, the development of atrophy and replacement of specialized connective tissues, insufficiency of the function of various body systems. Subcutaneous fat and skin are the main “depots” of amyloid fibrils. Their deposits are determined in the punctates of the skin long before the appearance of clinical manifestations of the pathological process.
Cutaneous amyloidosis is not an independent disease. This is a consequence of a systemic violation of metabolic processes. Skin manifestations may predominate in the clinical picture of the disease or be absent. They may appear earlier than the symptoms of internal organ damage or become a late manifestation of AA- (secondary) or AL- (primary) amyloidosis. The classification includes:
1 Systemic amyloidosis. Areas of amyloid accumulation are located everywhere in the body, including in the skin. The process can affect only the dermis or it extends to the epidermis, mucous membranes, subcutaneous fat. The constantly progressive lesion of internal organs leads to a significant limitation of the patient’s physical capabilities, which requires the adoption of radical measures aimed at achieving remission.
2 Local amyloidosis. It is the most favorable variant of the course of the disease, since the vital internal organs remain intact, and their function does not suffer. Pathology does not affect the life expectancy of a person and his physical abilities. Isolated (lichenoid) cutaneous amyloidosis can be both primary and secondary. Primary isolated skin lesion has three forms:
- Nodular. Amyloid is deposited in the skin throughout the body, but the characteristic manifestations of the disease cover limited areas of the skin of the lower extremities and inguinal region.
- Spotted. Complexes of proteins and polysaccharides are deposited in the papillary layer of the dermis, causing characteristic external manifestations. Local manifestations can be located everywhere.
- Nodular plaque. The skin and subcutaneous tissue, vascular walls, skin appendages (sweat and sebaceous glands, hair follicles) are affected. The elements characteristic of this form of cutaneous amyloidosis are located on a limited area of the lower extremities.
Primary systemic amyloidosis
A pathognomonic sign is the appearance of paraorbital hemorrhages when coughing, straining. This is due to the defeat of the intima of small vessels. Capillaries become brittle and easily damaged. Less often, skin induration develops, resembling that of scleroderma, papules, vesicles, nodules and plaques are formed. Seals gradually increase in size, merge.
The favorite localization of the elements are inguinal, axillary and other large folds of the skin, the pubic and hip area. At the initial stages of the formation of seals, the skin above them is pale, then gradually darkens, begins to peel off, becomes rough. Violation of the trophic skin as a result of damage to blood vessels and nerves can cause changes in the pigmentation of individual areas from complete loss of pigment to a pronounced increase in its production, alopecia. The affected areas are painless, itching is not characteristic.
Primary local amyloidosis
Localization of foci of amyloid deposition in nodular form: the anterior surface of the shins, rarely the coronal furrow, the glans penis. Foci up to 5 mm in diameter are located quite tightly, but do not merge. The surface of the nodules may peel off with small dirty-gray scales, contain horny spikes. The color of the formations ranges from pale to bluish. The skin at the site of the rash is compacted and is taken into the fold with great difficulty. The patient is worried about excruciating itching. As a result of scratching on the shins, bloody crusts and pronounced lichenification appear. Itching occurs both at the location of the nodules and in the area of unchanged skin due to the ubiquitous deposition of amyloid.
With spotted amyloidosis, the entire skin of the trunk and limbs is affected, more often the upper back. The spots have a brownish tint, slightly itchy. In some cases, small nodules may appear simultaneously with the spots. Nodular plaque amyloidosis is characterized by the development of single or multiple nodes up to 2 cm in diameter, mainly on the extensor surfaces of the shins. Nodes can merge into a single lumpy conglomerate, the surface of which is covered with horny layers and small scales. Excruciating itching leads to the appearance of linear combs, lichenification of the skin.
Secondary systemic amyloidosis
Protein-polysaccharide complexes are deposited in the skin and form seals that look like disks of different diameters. The skin above the seals is pale at first, and then acquires a dark brown or bluish color. Itching may have a different degree of intensity or be absent altogether. The skin lesion develops after changes in the internal organs appear.
Secondary local amyloidosis
External manifestations of the disease, as a rule, are absent. Glycoproteins accumulate in the skin relatively evenly without the formation of noticeable seals. Amyloid is detected by histological examination of samples taken from both internal organs and skin. Compression of the nerve endings of the skin can cause itching of varying degrees of intensity.
In systemic processes, disturbances in the work of internal organs come to the fore, which ultimately leads to the death of the patient. Significantly worsens the quality of life of itching, which exhausts a person, causes sleep disorders, decreased performance and social activity. Deposition of amyloid and concomitant inflammation lead to a significant increase in the size of the tongue and compaction of its tissues. Articulation, the process of chewing and swallowing is disrupted. Long-existing skin plaques, spots and nodules are a cosmetic defect, about which the patient may experience a full range of negative experiences.
Skin manifestations, disorders on the part of internal organs, changes in the results of laboratory and instrumental research methods in patients at risk allow to suspect the disease. To confirm the diagnosis , depending on the predominant localization of the lesion:
- Biopsy of internal organs. Tissue samples are taken from the gum mucosa, the inner surface of the colon, from the liver, kidneys. The detection of amyloid allows you to make the correct diagnosis and start treatment based on one study. The reliability of the method when taking mucosal samples is 70%, kidneys – 100%.
- Biopsy of subcutaneous fat. It is a more gentle method compared to taking tissue samples of internal organs. It can be used in people with a tendency to bleeding. Patients with primary amyloidosis often have insufficiency of the X-factor of blood clotting, which limits the ability of doctors to perform invasive diagnostic procedures. It is possible to detect amyloid in a skin biopsy in 80% of cases.
Differential diagnosis of cutaneous manifestations of amyloidosis in clinical dermatology is carried out with a number of diseases: verrucous lichen planus, myxedematous lichen, nodular verrucous neurodermatitis. In difficult cases, oncologists, hematologists, rheumatologists are involved in the diagnosis. Bone marrow puncture may be required to identify mutated plasma cells and amyloid.
An integrated approach to therapy is effective. Its volume is determined by the nature of clinical manifestations, the severity of local symptoms, the presence of concomitant diseases. The prognosis for the natural course of amyloid dystrophy is unfavorable, therefore, medical tactics may include:
- Systemic therapy. It is primarily aimed at suppressing chronic inflammation, reducing the production of precursor proteins. The second significant aspect is the resorption of amyloid deposits with dimethyl sulfoxide. The development of cardiac, renal, and hepatic insufficiency is the basis for the appointment of maintenance therapy.
- Local treatment. To reduce itching and accelerate the resorption of plaques, lotions with colchicine, dimexide, prednisone in the form of ointment are prescribed. The large size of the nodes is an indication for laser or surgical removal. The patient’s refusal of general treatment in the presence of indications makes local treatment of amyloidosis ineffective and significantly worsens the prognosis.
Prognosis and prevention
Cutaneous manifestations of amyloid dystrophy are not life-threatening. The patient can live with them for decades. The prognosis for the generalized form of amyloidosis is always cautious. Damage to the kidneys, heart, respiratory system organs quickly leads to death. Methods of prevention of dialysis amyloidosis, which develops in persons with impaired renal function, have been developed. There is an effect of identifying patients threatened by the development of amyloidosis and early initiation of treatment. At risk are people suffering from rheumatoid arthritis, other systemic diseases of connective tissue, chronic purulent-inflammatory processes in bones, lungs, soft tissues. Stabilization of the patient’s condition for the underlying disease is the most effective way to stop the development of skin manifestations of amyloid dystrophy.