Dermatology and veneorology

ВЫСШЕЕ ОБРАЗОВАНИЕ серия основана в 1 996 г.





DERMATOLOGY AND VENEREOLOGY
TUTORIAL

Under the general editorship of Professor O.A. Pritulo





                znanium.com




электронно-библиотечная система
Moscow INFRA-M
2023

УДК 616.5(075.8)
ББК 55.8я73

     Д36


      Reviewers:
         Kubyshkin A.V., Doctor of Medical Sciences, Professor, Head of the Department of General and Clinical Pathophysiology, Vice-Rector for Scientific Activities (Medical Institute of the Order of the Red Banner of Labor named after S.I. Georgievsky, Crimean Federal University named after V.I. Vernadsky);
         Karimov I.Z., Doctor of Medical Sciences, Professor, Head of the Department of Infectious Diseases (Medical Institute of the Order of the Red Banner of Labor named after S.I. Georgievsky, Crimean Federal University named after V.I. Vernadsky)






          Dermatology and venereology : tutorial / under the gen. ed. of Д36 Prof. O.A. Pritulo. — Moscow : INFRA-M, 2023. — 214 p. — (Higher Education). — DOI 10.12737/2021364.
          ISBN 978-5-16-018539-2 (print)
          ISBN 978-5-16-111531-2 (online)
          The tutorial contains data on the history of dermatovenereology, modern concepts of anatomy, physiology, pathomorphology of the skin and its appendages. Considerable attention is paid to the practical skills that the student must master when studying the course of dermatovenereology. The main issues of the clinic, diagnosis, differential diagnosis, prevention and treatment of the most important skin diseases and sexually transmitted diseases are described. In addition, situational tasks are given after each topic. Separate sections are devoted to writing a medical history and questions for independent extracurricular work of students.
          The content corresponds to the program of the discipline “Dermatovenereology”.
          The tutorial is intended for 4th year students of higher medical educational institutions.


УДК 616.5(075.8)
ББК 55.8я73








ISBN 978-5-16-018539-2 (print)
ISBN 978-5-16-111531-2 (online)


© Team of authors, 2023

                Team of authors





   Pritulo Olga A., Doctor of Medical Sciences, Professor, Head of the Department Dermatovenereology and Cosmetology (Medical Institute of the Order of the Red Banner of Labor named after S.I. Georgievsky, Crimean Federal University named after V.I. Vernadsky);
   Prokhorov Dmitry V., Doctor of Medical Sciences, Professor, Professor of the Department Dermatovenereology and Cosmetology (Medical Institute of the Order of the Red Banner of Labor named after S.I. Georgievsky, Crimean Federal University named after V.I. Vernadsky);
   Maraqa Marvan Ya.N., Candidate of Medical Sciences, Associate Professor, Associate Professor of the Department Dermatovenereology and Cosmetology (Medical Institute of the Order of the Red Banner of Labor named after S.I. Georgievsky, Crimean Federal University named after V.I. Vernadsky);
   Ngema Maria V., Candidate of Medical Sciences, Associate Professor, Associate Professor of the Department Dermatovenereology and Cosmetology (Medical Institute of the Order of the Red Banner of Labor named after S.I. Georgievsky, Crimean Federal University named after V.I. Vernadsky);
   Kuznetsova Marina Yu., Candidate of Medical Sciences, Associate Professor, Associate Professor of the Department Dermatovenereology and Cosmetology (Medical Institute of the Order of the Red Banner of Labor named after S.I. Georgievsky, Crimean Federal University named after V.I. Vernadsky);
   Kaud Dia, Candidate of Medical Sciences, Associate Professor, Associate Professor of the Department Dermatovenereology and Cosmetology (Medical Institute of the Order of the Red Banner of Labor named after S.I. Georgievsky, Crimean Federal University named after V.I. Vernadsky);
   Ispiryan Mikhail B., Candidate of Medical Sciences, Associate Professor, Associate Professor of the Department Dermatovenereology and Cosmetology (Medical Institute of the Order of the Red Banner of Labor named after S.I. Georgievsky, Crimean Federal University named after V.I. Vernadsky).

3

                Introduction





   Dermatovenereology is a science studying causes, clinical manifestations and methods of treatment of skin and sexually transmitted diseases. Study of this subject is very important for the doctor today, especially now, when family medicine takes the leading position in the general health care. Knowledge of this discipline gives an opportunity to reveal syphilis on time, differentiate skin diseases from infectious ones, and make a diagnosis of pemphigus and interstitial disease being a serious danger for the life of patients.
   This manual consists of thirteen themes, questions for independent students’ work, and practical skills for students. The book includes data of dermatology development, modern notion of anatomy, physiology, pathomorphology of skin and its appendages. Much attention is devoted to the practical skills of students, which every student must master studying dermatovenereology course. Main problems of clinics, diagnostics, differential diagnostics prophylaxis, and treatment of the most important skin and venereal diseases dermatological aspects of HlV-infection.
   Besides, situational tasks and test questions are added at the end of each theme. Steps of medical history taking and independent students’ work are included into the book.

4

                CONTENT MODULES




                Content module 1
                SKIN





1.1. SKIN ANATOMY AND HISTOLOGY
   Skin is an external body layer, independent metabolically active organ. Its size is 1.6-1.8 m2. Its weight is approximately 16-20% of the total body weight. Human skin consists of epidermis, dermis, and hypodermis. There are also additional skin components such as hair, sweat, and sebaceous glands. Epidermis is an external skin layer. It consists of continuously changing epithelial cells (epitheliocytes, keratinocytes), which are always in the process of differentiation beginning with the lower slightly differentiated basal layer and continuing in the direction of the upper corneous layer. Epidermis consists of several types of cells having different embryonic origin — epitheliocytes, melanocytes, intraepidermal macrophages (Langerhans’ cells), and Marcellus’ cells and is divided into 5 layers — basal, spinous, granulated, lucid and corneous ones reflecting different stages of elements differentiation.
   Cellular homeostasis support in epidermis totally depends on the correlation between the cells being formed and dying ones. Many factors make an influence on these processes: the level of interactions of epitheliocytes with other cells of epidermis; the quality of epitheliocytes adhesion with each other and basal membrane; different skin diseases; age and sex of the human being; climatic conditions. Epidermis doesn’t have absolutely estimated thickness. It varies in different body parts: in the palm area it is about 0.1 mm, on the soles it is from 0.8 to 1.4 mm; on the rest body parts it is less than 1mm.
   Basal layer (stratum bazale) — epitheliocytes located on the basal membrane are embryonic cells. Merkel cells and melanocytes are also in the basal layer. Basal cells are located on the basal membrane and have a cylindrical form. Their nucleuses are oval by shape, intensively colored with hematoxylin and rich in chromatin. Numerous organelles: mitochondria, Golgi complex, ribosomes, pol-iribosomes, lysosomes, centrioles, endoplasmic reticulum, tonophilaments forming the cytoskeleton, and other additional components (melanin granules, fat

5

drop) are found in cytoplasm. Basal cells proliferation and tonophila-ments synthesis cause a great amount of ribosomes.
   Cell-to-cell conjugation occurs at certain intervals due to the des-mosomes located at the place of two neighboring cells contact This connection plays an important role in the structural integrity of epidermis and provides epitheliocytes regulation — their proliferation, movement and differentiation. Desmosomes contain 71% of proteins, 14% of carbohydrates and 10% of lipids, mainly cholesterol and phospholipids. Sometimes high mitotic activity of sprout cells makes them to be the target for different undesirable influences, for example, UV-radiation, and then it can lead to the tumor of skin.
   Spinous layer (stratum spinosum) consists of 3-8 rows of cells, more differentiated than basal ones. Directly above the basal layer they have a polygonal shape and they become flat in the upper part of spinous layer. Spinous layer cells conjugate cell-to-cell like basal ones with the help of desmosomes, the number of which is greater and it gives them more strength. Ultrastructure of spinous cells is similar to that of basal one but it differs by more developed complex of tonophilaments, less organelle content, and pigment absence. Lamellar bodies appear in the upper part of spinous layer (lamellar granules, keratinocytes, Odland’s bodies) and locate on the cells periphery. They sometimes come in contact with plasmatic membrane or pass into the intercellular spaces. These organelles contain lipids, phospholipids, free sterols, ceramides, and glucosylceramides. Besides, a large amount of hydrolytic enzymes such as acid phosphatase, nucleoside diphosphatase, and phospholipases can be found in lamellar granules. Granules release their content into intercellular space forming epidermal lipid barrier. Internal epidermal macrophages — Langerhans’ cells are in the spinous layer too.
   Granular layer (stratum granulosum) is presented by several lines of flat epitheliocytes. The cells of granulated layer are also connected by desmosomes. Their ultrastructure is similar to that of the lower layers but they lose intercellular contact layer on the border with corneous layer. Granular cells are identified by the typical cytoplasmic basophilic keratohyalin granules. Keratohyalin granules are tightly connected with the bands of tonofilaments and consist mainly of profilaggrin.
   Clear layer (stratum lucidum) is well determined only on the palms and soles and consists of tightly located, prolonged and flat cells which don’t have any nucleus. In this layer epitheliocytes continue to synthesize and modify proteins and enzymes which take part not only in keratinization but also in the programmed cell destruction. As a result destruction of majority of the structures of granulated cells including


6

their nuclei occurs. Such form of destruction morphologically and biochemically corresponds to apoptosis (programmed cell death).

Corneous layer (stratum corneum)
   The final period of epitheliocytes life occurs in the corneous layer, where they turn into polygonal corneous cells without any nuclei. Such epitheliocytes got a name of “corneus squamae” Corneous layer protects the skin from liquid loss and external harmful substances penetration, and as well as mechanical insults. This layer is represented by the lines of corneous squamae and is more evident on the palms and soles. On the other parts of body it’s rather thin. Thickness of corneous layer depends on the sex, age and skin diseases presence. Squamae are separated from each other by intercellular spaces where desmosomes having a form of dense structures could be seen.
   So epidermis is an integrated functional and anatomical skin structure. Conditional division of epidermis into several layers reflects, first of all, the process of epitheliocytes differentiation, having several stages: undifferentiated cells of basal layer are divided uninterruptedly and in addition, some amount of them is left on its place and another is differentiating and moving up; in the spinous layer cells become more differentiated and polygonal by form; in the granular layer the disintegration of cell nuclei and organelle happens; the process of differentiation of epitheliocytes is over in the corneous layer, in which the cells, being already corneus squamae (lamellae), independently exfoliate from the surface of the skin.
   Dermis is the main component of skin connective tissue providing its flexibility and strength. It protects the organism from mechanical traumas, takes part in thermoregulation, and contains great number of vessels and nerves.
   Dermis varies greatly in its thickness on different body parts: for example, it is very thin on the eyelids (0,6 mm), on the back, palms and soles it is very thick (3 mm and more). Totally dermis consists of cells and intercellular matrix. Two layers form the dermis: papillary and reticular. Besides differences in its position, they differ in the degree of connective tissue organization, number of fibrous structures, cells, nerve filaments, and vessels.

Papillary layer (stratum papillaris)
   Collagen and elastic fibers are the base of this layer. A developed network of collagen and elastic fibers is formed due to the synthesis of a great number of fibroblasts, having a high level of metabolic activity.

7

   Reticular layer (stratum reticularis) of dermis is formed mainly by collagen fibers of big diameter interlaced in big bundles. Mature elastic fibers interlace with bundles of collagen fibers and make dermis elastic and resilient. In healthy skin the size of elastic fibers and bundles of collagen of reticular layer increases nearer to hypoderma. Conditionally reticular layer is divided into upper and lower zones. It characterizes, first of all, the degree of difference in size and fibrous connective tissue feature. In the upper zone of reticular layer one can find mainly collagen fibers and bundles and also horizontally oriented elaunin elastic fibers. This region is rich with fibroblasts and other connective cells and in case of inflammation it is rich with leukocytes and lymphocytes. The upper zone has weaker mechanic properties as compared to deep lower zone of reticular dermis layer and, probably due to this fact, it is inclined to the development of different pathological processes, for example, to the loss of elastic fibers.

Dermis cells
   Fibroblasts are the main dermis cellular type. They are mesenchym-atous cells of connective tissue responsible for synthesis and lysis of fibrous joints and a plenty of other soluble compounds of intracellular matrix. One and the same fibroblast is capable to synthesize simultaneously several types of protein substances, e.g. collagen and elastin. Immature cells beginning from germ are sequentially differentiated until they reach their maturity and after that fibroblasts are subjected to degeneration or transformation. In dermis there are also histiocytes, the cells having stellate, dendritic or rather rare, spindle form. As a rule, they are found in large amounts in the papillary layer and upper part of reticular layer of the dermis. Histiocytes are immune component cells functioning as effector cells of afferent link of the immune response. In case of inflammatory diseases, e.g. psoriasis and eczema, the number of these cells increases, they become activated evoking expression of different inflammation markers. Another type of histiocytes — macrophages — have bone marrow origin. Penetrating into the bloodstream they turn into monocytes and then migrate to dermis where they are subjected to differentiation. Macrophages are active phagocytes, take part in the antigen processing and presentation of it to the immune-component lymphocytes. They have bactericidal and tumour effect due to the lysosome, superoxides, peroxides production, synthesize different growth factors, cytokines and other immune modulating molecules, and hemopoietins.
   Tissue basophiles of dermis are the cells, predecessors of which were in the bone marrow (CD34+) and are distributed along all con

8

nective tissue. Their greatest concentration is observed in the papillary layer of dermis. Tissue basophiles synthesize lots of mediators and at activation they are first effectors of allergic reactions. They also take part in the anti-tumor immune response and at tumor cells appearance they release tumor necrosis factor alpha-a substance having cytotoxic activity. Besides, tissue basophiles play an important role in the antiparasite protection, stimulate chemotaxis, activation and proliferation of eosinophils, intensify phagocytosis, change vascular tone and patency; stimulate connective tissue reparation.
   Intercellular matrix of the dermis consists of 3 components: main substance, adhesive proteins and fibrous structures (collagen, elastic and reticular fibers). It performs different functions: provides mechanical contacts between cells, arranges firm structures, forms the ways of cellular transmission along which they can move. Main dermal substance is formed in a special way permitting the cells to move freely and regulate skin deformation. It is jelly-like amorphous substance consisting of glycosaminoglycans (GAGs), glycoproteins, proteoglycans, soluble collagen, and enzymes and split products. GAGs are linear polymers consisting of repeating disaccharides providing necessary hydration and viscosity to dermis. That’s why dermal saturation with GAGs in the young age keeps skin smooth, without wrinkles. An increase in GAGs level is observed during wounds healing on the skin, when the cells migration is one of the most significant points of the reparation process. Sulfated GAGs become prevalent at the time of dermis aging; and the level of hyaluronic acid being one of the most important components of GAGs begins to reduce. Proteoglycans are GAGs in the form of high-molecular polymers with the protein core to which hyaluronic acid is linked (hyaluronate). Their main role consists in the binding of growth factors and cytokines and in relieving of cells interaction with fibrous structures of territorial matrix. Due to these properties proteoglycans can influence proliferation, differentiation, reparation and skin morphogenesis.

Adhesive proteins
   Fibronectin, laminin, thrombospondin (TSP) are the most important adhesive proteins. These polyfunctional proteins are capable to combine different compound components of intercellular matrix. Besides they also provide fixation of cells in the intercellular matrix interacting with membranous receptors-integrins. Adhesive proteins, due to the cells, collagen and elastic fibers adherence, take part in the process of homeostasis of derma promoting adhesion, migration, maturation, and differentiation of cells and other dermal components.

9

Fibrous structures of Collagen fibers
   Collagen fibers are the main components of dermis and compose 75% of dry mass of skin and provide its elasticity and firmness. By now more than 25 different types of collagen have been determined.
   At one of the ends collagen molecule is attached by cross-links, the number of which increases while aging. Collagen molecules are capable of spontaneous aggregation with the formation of more complex struc-tures-microfibrils and fibrils. Fibroblasts take part in the formation of collagen fibers. In the dermis of mature person interstitial fibrillar collagen (I, III and V type) is one of the largest collagen fractions: collagen type I constitutes approximately 80-90% collagen type III constitutes 8-12%. Collagen type I is found in the reticular layer in great amount; collagen type III is found mainly in the papillary one.
   Elastic fibers constitute 1-3% of dermis and form wide net. They are also found in the vessel walls of skin and membranes of hair follicles. A net of elastic fibers provides the skin with elastic, resilient properties. Elastic fibers are also produced with the help of smooth muscular cells in contrast with collagen, synthesized by only fibroblasts. Elastic fibers consist of two main components — elastin and fibrils. Elastins are polymer proteins having cross-linked structure and fibrils are glycoproteins. The elastic fibers production in dermis is very slow, but can be accelerated under ultraviolet radiation and in case of inflammation.
   Reticular fibers (argyrophilic fibers) are found mainly at the border of dermis and epidermis, around the vessels, sweat and sebaceous glands, and hair follicles. These fibers are similar by their composition to collagen fibrils but have smaller diameters. The largest number of reticular fibers can be found in the healing wounds. At that time hyperproduction of collagen in fibroblasts occurs.
   Hypodermis — subcutaneous cellulose — performs many functions — serves as a place of production and accumulation of fat. It is a reservoir of energy. It is “amortization pillow” in case of traumas and is characterized by dynamic metabolism of lipids. Maximal volume of fat tissue is located in hypodermis. Subcutaneous fat thickness differs depending on the part of the body. For example, its thickness in the anterior abdominal wall can reach 3 cm, and in the region of forehead it can be several millimeters. A transition zone located between fibrous connective tissue and hypodermic tissue saturated with fat is a boundary between deep dermal reticular layer and hypodermis. Despite of conditional boundary presence, hypodermis and dermis are firmly structurally and functionally joined by passing through them nerves and vessels and also by numerous cutaneous adnexa. Bulbs of the hair follicles as well as secretory portions of eccrine sweat glands are located in hypodermis. Adipocytes

10