Pachydermoperiostosis

Pachydermoperiostosis (Greek pachus - thick, dense; derma - skin and periostosis - non-inflammatory change of the periosteum) is a disease, the leading symptom of which is massive thickening of the skin of the face, skull, hands, feet and distal parts of long tubular bones. In 1935, French doctors H. Touraine, G. Solente and L. Gole first identified pachydermoperiostosis as an independent nosological unit.

Causes pachydermoperiostosis

The causes and pathogenesis of pachydermoperiostosis are currently poorly understood. It is known that pachydermoperiostosis is a hereditary disease with an autosomal dominant type of inheritance with variable expressivity, usually manifesting itself in the postpubertal period. Familial forms have also been described. The ratio of patients among men and women is 8:1. Pachydermoperiostosis is a rare hereditary disease. The first signs of the disease appear during puberty, and the full symptom complex is formed by the age of 20-30.

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Pathogenesis

Morphologically, the disease is characterized primarily by massive proliferation of fibrous structures of the dermis and subcutaneous tissue with pronounced ingrowth of fibrous connective tissue into the underlying tissue, which causes intimate fusion of the skin with them. Fibrous hyperplasia also occurs in the wall of blood and lymphatic vessels of the dermis; the lumens of such vessels are usually "gaping"; some of them are thrombosed. There is a significant increase in the number of mature sweat and sebaceous glands, sometimes hyperplasia and/or hypertrophy of the glandular cells that form them. Chronic inflammatory infiltrates are also found in the skin, secondary hyperkeratosis and acanthosis are also observed. Fibrosis is observed in the aponeurosis and fascia.

In the bones of the skeleton, especially tubular, large and small, periosteal ossification occurs - diffuse layering of osteoid tissue on the cortex. It can reach 2 cm or more in thickness or be limited in the form of osteoma. This process spreads both endosteally and periosteally. Sometimes fibrous thickening of the periosteum and disruption of bone architecture are observed. Immature bone substance is often found. Desolation of the vessels that feed the bone tissue is noted. In the joints - hyperplasia of the integumentary synovial cells and pronounced thickening of the walls of small subsynovial blood vessels due to fibrosis. Fibrosis of the vessel walls, especially blood vessels, can also occur in internal organs.

The epidermis is slightly changed, the dermis is thickened due to an increase in the number of collagen and elastic fibers, fibroblast proliferation, small perivascular and perifollicular lymphohistiocytic infiltrates, widening of the mouths of hair follicles with accumulation of horny masses in them, hyperplasia of the sebaceous, and sometimes simultaneously sweat glands are noted.

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Symptoms pachydermoperiostosis

This disease is relatively rare. Its clinical features, diagnostics and treatment are little known to a wide range of endocrinologists. A significant proportion of patients with pachydermoperiostosis are mistakenly diagnosed with acromegaly, which leads to the use of inadequate treatment measures. In this regard, it is appropriate to present the clinical features, modern methods of diagnostics and treatment of pachydermoperiostosis.

Clinical symptoms in women are much less pronounced, but there are patients with a complete form and severe course of pachydermoperiostosis. The onset of the disease is gradual. The clinical picture completes its development in 7-10 years (active stage), after which it remains stable (inactive stage). Characteristic complaints of pachydermoperiostosis are a pronounced change in appearance, increased oiliness and sweating of the skin, a sharp thickening of the distal parts of the limbs, an increase in the size of the fingers and toes. Appearance changes due to ugly thickening and wrinkling of the skin of the face. Pronounced horizontal folds on the forehead, deep grooves between them, an increase in the thickness of the eyelids give the face an "aged expression". A characteristic feature is folded pachydermia of the scalp with the formation of moderately painful, rough skin folds in the parietal-occipital region, resembling brain convolutions - cutis verticis gyrata. The skin of the feet and hands is also thickened, rough to the touch, fused with the underlying tissues, and does not lend itself to displacement or compression.

The production of sweat and sebum increases significantly, especially on the face, palms and plantar surfaces of the feet. It is of a permanent nature, which is associated with an increase in the number of sweat and sebaceous glands. Histological examination of the skin reveals its chronic inflammatory infiltration.

In pachydermoperiostosis, the skeleton is altered. Due to the layering of osteoid tissue on the cortex of the diaphyses of long tubular bones, especially the distal sections, the forearms and shins of patients are enlarged in volume and have a cylindrical shape. Similar symmetrical hyperostosis in the metacarpal and metatarsal areas, phalanges of the fingers and toes leads to their growth, and the fingers and toes are club-shaped, deformed like "drumsticks". The nail plates have the shape of "watch glasses".

A significant proportion of patients experience arthralgia, ossalgia, hip, knee, and less frequently ankle and wrist arthritis. The joint syndrome is associated with moderate hyperplasia of the synovial cells and severe thickening of small subsynovial blood vessels and their fibrosis. It is not severe, rarely progresses, and limits the ability to work of patients only with severe joint syndrome, which is rare.

In 1971, J. B. Harbison and C. M. Nice identified 3 forms of pachydermoperiostosis: complete, incomplete and truncated. In the complete form, all the main signs of the disease are expressed. Patients with the incomplete form have no skin manifestations, while those with the truncated form have no symmetrical periosteal ossification.

The grotesque appearance, constant sweating and greasy skin have a negative impact on the mental status of patients. They are withdrawn, focused on their feelings, and isolate themselves from others.

Diagnostics pachydermoperiostosis

When diagnosing pachydermoperiostosis, it is necessary to take into account the form and stage of the pathological process. Along with characteristic complaints and the appearance of patients, the most informative is the X-ray examination. On X-rays of the diaphyses and metaphyses of tubular bones, assimilated hyperostoses reaching 2 cm or more are revealed. The outer surface of the hyperostoses has a fringed or needle-like character. The structure of the skull bones is not changed. The sella turcica is not enlarged.

Bone scintiscanning with methylene diphosphonate ^99Tc reveals a linear pericortical concentration of the radionuclide along the tibia and fibula, radius and ulna, as well as in the metacarpal and metatarsal regions, phalanges of the fingers and toes.

The results of thermography, plethysmography and capillaroscopy indicate an increase in the blood flow velocity and tortuosity of the capillary network, an increase in temperature in the thickened terminal phalanges of the fingers. The similarity of clinical manifestations and anatomical findings in pachydermoperiostosis and Bamberger-Marie syndrome suggests a common pathogenetic mechanism. In the early (active) stage of pachydermoperiostosis, vascularization and temperature of the distal parts of the fingers are increased, i.e. there is local activation of metabolism. Its similar increase is noted in Bamberger-Marie syndrome in those areas where there is visible excessive tissue growth. In the late (inactive) stage, obstruction and insufficiency of the capillary network, uneven contours of the capillary loops are revealed, which leads to a decrease in the blood flow velocity in the terminal phalanges of the fingers and cessation of their further enlargement. Similar changes occur in the periosteum: maximum vascularization in the early stage of the disease and relative devascularization in the late stage.

General blood and urine tests, basic biochemical indices in patients with pachydermoperiostosis are within normal limits. The level of pituitary tropic hormones, cortisol, thyroid and sex hormones is unchanged. The reaction of somatotropic hormone to glucose load and intravenous administration of thyroliberin is absent. Some works mention an increase in the content of estrogens in the urine of patients, which, according to the authors, is associated with a violation of their metabolism.

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Differential diagnosis

Pachydermoperiostosis should be differentiated from acromegaly, Bamberger-Marie syndrome and Paget's disease. In Paget's disease (deforming osteodystrophy), the proximal tubular bones are selectively thickened and deformed with coarse trabecular bone remodeling. The disease is characterized by a decrease in the facial skeleton and a significant increase in the frontal and parietal bones, forming a "tower" skull. The size of the sella turcica is unchanged, there is no proliferation and thickening of soft tissues.

The most important issue is differential diagnostics of pachydermoperiostosis and acromegaly, since if acromegaly is diagnosed incorrectly, irradiation of the intact interosseous-pituitary region leads to the loss of a number of tropic functions of the adenohypophysis and further aggravates the course of pachydermoperiostosis.

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Treatment pachydermoperiostosis

Etiopathogenetic treatment of pachydermoperiostosis has not been developed. Cosmetic plastic surgery can significantly improve the appearance of patients and, thus, their mental status. In some cases, a good effect is observed with local (phono- or electrophoresis on damaged skin) and parenteral use of corticosteroids. Complex therapy should include drugs that improve tissue trophism (andecalin, complamine). In recent years, laser therapy has been successfully used for treatment. In the presence of arthritis, non-steroidal anti-inflammatory drugs are highly effective: indomethacin, brufen, voltaren. Radiation therapy to the interstitial-pituitary region is contraindicated for patients with pachydermoperiostosis.

Forecast

The prognosis for recovery of patients with pachydermoperiostosis is unfavorable. With rational treatment, patients can maintain their ability to work for a long time and live to old age. In some cases, due to the severity of the joint syndrome, there is a persistent loss of ability to work. There are no special methods for preventing pachydermoperiostosis. They are replaced by careful medical and genetic counseling of the families of patients.

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