Methods of Examination. Complaints.Patients with diseases of the bones and muscles and with systemic affections of the connective tissue can produce various com­plaints

Inquiry

Complaints. Patients with diseases of the bones and muscles and with systemic affections of the connective tissue can produce various com­plaints. These would be commonly pain in the joints, spine, or muscles, hindered movements in the morning, sometimes muscular weakness, and elevated temperature. Symmetrical affections of minor joints of the hands

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and soles, their tender articulation (active and passive) and also tender palpation are characteristic of rheumatoid polyarthritis. Major joints (wrist, knee, elbow, hip) are affected less frequently in this disease. Pain becomes more intense by night, in cold and damp weather. At later periods of the disease, the joints are distinctly disfigured, and their articulation is limited (to ankylosis). A frequent complaint is difficult and limited ar­ticulation and movement in the morning; the movements become easier by the end of the day. Rheumatism and arthrosis deformans are characterized by a distinct tendency to affection mainly of the major joints. In arthrosis deformans, pain develops mainly under load on the affected joint (in walk­ing, stepping on the affected leg). Pain intensifies by the evening as a result of daily exercise. In ankylosing spondyloarthritis (Bekhterev's disease), pain is localized in the spine and the sacrolumbar articulations. Pain develops after a long stay in a fixed position (usually during night sleep). At later stages of the disease when changes in the spine become pronounc­ed, pain becomes permanent; it occurs not only during night but also in physical exertion and during weather changes. Specific changes in the spine of a patient can be revealed by the physician at first sight. In rare cases, the joints are also involved in this disease.

Rheumatoid polyarthritis is characterized by the predominant affection of the major joints and by the " wandering" character of affection: various joints are involved one after another, while pain in the previously affected joint disappears (within a few days or weeks) and articulation is restored. Another specific feature of rheumatoid polyarthritis is that all changes in the affected joints and periarticular tissues disappear and leave no trace after the acute rheumatic process abates.

Acute attacks of pain, mainly in the metatarsophalangeal joints of the great toes (less frequently in other joints), which arise mainly during night and predominantly in the aged and middle-aged males, can be a symptom of gout, the disease in which the purin metabolism is upset.

Thus, if a patient complains of pain and difficult movement of joints, the character of this pain should be studied thoroughly to determine its location, intensity, lenght, effect of exercise and other factors that can pro­voke pain, etc.

Muscular pain also differs in its character. Pain can be disseminated to indicate involvement of the entire muscular tissue. Acute attacks of pain in this or that group of muscles that last for several days (often after exposure to cold) suggest myositis. Pain in the calf muscle during walking (usually in the presence of marked atherosclerosis of the arterial vessels in various organs, in frost-bitten legs, in heavy smokers) is characteristic of stenosing arteries of the lower extremities (due to atherosclerosis, obliterating endar-theritis, and certain other diseases). Pain discontinues when the patient

stops walking (the syndrome of intermittent claudication). The patient would often complain of cold in the legs which makes him wear woolen socks and winter boots even in warm weather. Muscular pain is also a symptom of trichinelliasis, cysticercosis, or myositis of infectious, occupa­tional (chronic exposure to low or high ambient temperature, vibration or other harmful industrial factors), and traumatic origin. It is important to determine localization, intensity, character, and duration of the pain.

Elevated temperature and various skin lesions (petechia, erythema, ur­ticaria, etc.) are frequent symptoms of systemic diseases of the connective tissue, the so-called collagenoses, and also allergoses. A rapidly developing (without apparent cause) local oedema of the skin and subcutaneous tissue is frequent in Quincke's disease (allergic oedema attended by skin itching and burning; this may be caused by food, bacterial or other allergy).

Muscular weakness (hypotonia) develops not only in prolonged rest (immobilized patients with grave diseases) but also in some neurological diseases (myatonia, myasthenia, progressive muscular dystrophy, etc.). Each of these diseases has its special features. Myasthenia, for example, is characterized by pathological muscular fatigue. Contractions of a muscle may first be quite normal, but in repeated movements the muscular force decreases to complete loss of contractile power. After a short rest, the mus­cle again becomes capable of contracting. Muscles lifting the upper eyelid and muscles participating in swallowing and mustication are usually af­fected in the first instance.

Weakening of active muscular movements is called paresis, while a complete loss of power to perform movements is known as paralysis.

Paresis and paralysis may affect any muscle or group of muscles in the presence of impaired innervation. Clinicists (internists included) would commonly observe patients with affected innervation of muscles of only one extremity (monoplegia); sometimes both legs are paralysed (paraplegia), or the extremities on one side are only affected (hemiplegia). Tetraplegia (paralysis of all four extremities) occurs in rare cases. Paralysis and paresis can develop due to affection of peripheral nerves, spinal cord (injury, compression, tumour growth, etc.), of certain parts of the brain (in thrombosis of the cerebral vessels, e.g. in atherosclerosis, embolism, or cerebral haemorrhages). Spastic paralysis with subsequent atrophy of the paralysed muscles occurs in affection of the central neuron.

The patient sometimes complains of cold and pale fingers (in rare cases of the ear or nose). This may occur at low ambient temperatures, injuries, and psychic stress. This is attended by pain and hyposensitivity of the skin to pain and temperature variations; this condition may develop after an at­tack of hyperaesthesia. Such attacks are characteristic of Raynaud's

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disease (vasomotor neurosis). This condition is often the first symptom of a grave collagen disease, systemic scleroderma.

Anamnesis. Information concerning the onset and development of the disease should be collected. Many chronic diseases of bones and muscles develop insidiously and progress slowly. The disease becomes apparent on­ly at later periods. Acute vigorous onset is characteristic of rheumatism (often in 2-2.5 weeks following tonsillitis, scarlet fever or acute respiratory infection), some forms of rheumatoid arthritis, and infectious arthritis (caused by brucellosis, dysentery, gonorrhoea, etc.). Acute affec­tion of muscles occurs in myositis, acute paralysis, including paralysis unassociated with injuries. Hemiparesis in patients with atherosclerosis or arterial hypertension of any origin occurs not infrequently. Hemiparesis develops due to thrombosis of the cerebral vessels, cerebral haemorrhages in mitral heart diseases concurrent with cardiac fibrillation and throm-boendocarditis (due to embolism and arterial obstruction) and in some other diseases. Nodular periarteritis (mainly in the young) and systemic lupus erythematosus begin acutely only in rare cases.

In some cases, it is possible to establish the factor that provoked the disease of the joints and systemic affections of the connective tissue. In most cases, these diseases are preceded by an infectious disease or over-cooling of the body; sometimes the disease follows irrational use of medicinal preparations (sulpha drugs, antituberculosis preparations, an­tibiotics, vaccines, sera, etc.), or develops due to perverted hypersensitivity to these preparations.

Anaphylactic shock may develop in patients with acquired or con­genital hypersensitivity to certain medicines given parenteral-ly or when carrying out some tests, e.g. Pirquet, or Mantoux test. Some medicines can cause anaphylactic shock due to a contact with the mucosa (eye conjunctiva, mouth mucosa). But a slow development of an allergic reaction to medicinal preparations (antibiotics, sulpha drugs, butadione, thiamine, procaine, etc.) is more frequent: skin itching, dermatitis, ur­ticaria, fever, arthralgia, myalgia, lymphadenopathy and other types of medicamentous allergy develop in several days. The remarkable advances in pharmacology help control many diseases, but they also bring along some negative effects, e.g. development of the so-called medicamentous diseases. Therefore, when questioning the patient, it is necessary to find out if he took some medicines, and if he did, then for what diseases, and what was the allergic reaction, if any.

A certain (unknown) role belongs to the hereditary predisposition of the patient to certain diseases of the bones and muscles, systemic diseases of the connective tissue, and various allergic affections (bronchial asthma, urticaria, etc.).

Physical Examination

INSPECTION

A glance at a patient can sometimes be enough to assess his health and diagnose the disease, e.g. anaphylactic shock, an attack of asthma, skin le­sions such as erythema, urticaria, or local angioneurotic oedema (usually localized on the face), and suggest the allergic nature of the affection. Changes in the skin become more pronounced in grave cases: vesicles and even necrotic lesions develop on the skin and mucosa.

The posture of the patient, e.g. a marked kyphosis of the chest in com­bination with lumbar lordosis and limited mobility of the spine (the trunk of the patient is fixed in the inclined " position of a beggar") suggests ankylosing spondyloarthritis (Bekhterev's disease). Affections of the spine, joints, acute inflammation of muscles (myositis) limit the patient's mobili­ty and sometimes immobilize him completely. The gait of the patient is quite informative for diagnosis. The paralytic gait of a patient with hemiplegia is characterized by the dragging limb. Paretic gait is characterized by slow movements of the patients and shuffling. It occurs in contracture of the extremities, paresis of the spinal origin. Unilateral affec­tion of joints of the lower extremities makes the patient spare the affected limb (limping on account of pain). It should be remembered that the hip joint is commonly affected in tuberculosis (tuberculous coxitis) usually in children; at later stages of the disease, ankylosis develops, the growth of the affected extremity is delayed, and the muscles become atrophied. Acute gonitis in adults can be of gonorrhoeal nature. Deranged innervation of muscles (paralysis, paresis of various nature), congenital myopathy (a group of diseases that are the subject of detailed discussion in the course on nervous diseases) are also important for the gait of a patient. Patients with grave disorders of muscular innervation are completely immobilized.

Marked deformation of small joints of the hand and foot is characteristic for rheumatoid arthritis. Disfigured terminal phalanges of the fingers with sclerotically changed skin on them (with necrosis in grave cases), or specific stretching folds round the mouth, especially in young women, suggest systemic scleroderma (collagen group of diseases). Cramped muscles (usually flexor muscles) are sometimes revealed on in­spection of the patient (development of contracture).

Erythema of the face skin, butterfly distribution of eruptions on the forehead (also mostly in young women) suggest a grave systemic di­sease of the connective tissue—systemic lupus erythematosus. Focal sclerotic changes on the skin of variable size are characteristic of local scleroderma.

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Chapter 11. Diseases of Bones, Muscles, Connective Tissue.

PALPATION;.

When examining the skin by palpation, the physician can reveal in­creased dryness, e.g. in systemic scleroderma, indurative oedema, and (at later stages of the disease) atrophy of the skin and focal calcinosis of soft tissues, mainly of the fingers and around major joints. Consolidation of muscles may occur in systemic scleroderma and dermatomyositis. The muscles are also consolidated and become tender in ordinary myositis. In the presence of Raynaud's syndrome, palpation confirms abnormally low temperature of the skin of the extremities, especially of the terminal phalanges of the fingers.

Palpation of the joints reveals hyperthermia and oedema of the skin around them (in acute affections), tenderness and deformities of the joints. A thorough palpation can show whether only the joint or the surrounding soft tissues are also involved. In some cases, palpation can reveal that, despite tenderness of the joints and pain in them during movements, the joints are not affected by pathology.

Palpation is also used to study passive mobility of various joints; limited activity of joints can be due to pain in arthritis or arthrosis, and also in ankylosis (i.e. in articular immobility). In the presence of in­complete ankylosis, the movement may first be unobstructed, but then sud­denly discontinue as if hindered by some insurmountable barrier. Special diagnostic techniques are sometimes used. In cases suspected for coxitis (inflammation of the hip joint), overextension of the stretched leg should be tried. The patient lies in the prone position. The movement of the af­fected leg is limited in coxitis due to developing pain and reflex muscular contracture. Flexion and rotation in the affected joint should be tried with the patient lying on his back. In order to measure accurately the angle be­tween two articulating bones through which an affected leg can move, a special instrument, known as a goniometer, is used. It should be remembered that the joint function can also be limited by cicatricial shrinkage of muscles or tendons due to past myositis, inflammation of ten­dons or their sheaths, or wounds. Inspection of the skin of the extremities, palpation of the muscles and tendons can reveal the cause of limited ar­ticulation. Palpation of the joint can reveal fluctuation in the presence of acute inflammation with ample transudate in the joint, or in the presence of purulent exudate.

By giving passive movements to all joints one after another and by palpating the muscles, it is possilbe to determine their tension. Contractile muscular tension, which depends on dysfunction of the lower motor neuron, and plastic tension which shows the condition of the internal medium of myofibrillae, are distinguished. Muscular hypotension and

hypertension are possible. Hypotonic muscles are flaccid to the touch, the belly of long muscles is not pronounced, passive movements are possible in the full extent, and sometimes even in a greater extent than of normal mus­cle. The joints are loose. When the muscle is passively stretched, the ex­aminer does not feel any muscular resistance. Muscular hypotension occurs mostly in affections of the peripheral nerves and prolonged muscular inac­tivity (e.g. when the patient keeps his bed for a long period for some grave disease). Muscular hypertension arises as a result of increased reflex muscular tension in the presence of affected pyramidal tracts; the muscles are firm and difficult to stretch passively; muscular resistance increases with the speed and abruptness of passive movements.

In order to obtain a complete impression of the muscular condition, the force of muscles should be assessed. Two methods are used for the pur­pose. The patient may actively resist the physician's attempt to flex or ex­tend his extremity (static force), or, on the contrary, the patient tries to overcome the resistance of the physician's hand (dynamic force). There are special instruments, dynamometers, and dynamographs which determine the muscular power of various groups of muscles.

Instrumental and Laboratory Methods

LABORATORY DIAGNOSIS

Laboratory diagnosis of systemic affections of the connective tissue is used mainly for determining activity of inflammatory or destructive pro­cesses in collagen tissue.

An active pathological process in these systemic diseases alters the con­centration and qualitative compostition of glycoproteins in the blood serum. Glycoproteins are biopolymers of protein and carbohydrate groups. Glycoproteins are component parts of the cell membrane; they cir­culate in the blood as transport molecules (transferrin, ceruloplasmin). Some hormones, enzymes, and immunoglobulins are also glycoproteins.

Glycoproteins are determined by chemical and electrophoretic methods. Most chemical methods are based on the determination of the carbohydrate component of the glycoprotein molecule by using various colour reactions with subsequent colorimetry. The principle of the elec­trophoretic determination of glycoproteins is the same as in electrophoretic separation of protein fractions of the blood serum. Schiff's reagent (con­taining basic fuchsine) is used for staining in the determination of glycoprotein fractions on electrophoregrams. The relative content of glycoprotein fractions in the blood of a healthy individual is as follows (in per cent): ablumins 10.4-16.6, a_rglobulins 14.2-18.3, a₂-globulins 24.8-31.8, /3-globulins 21.7-25, and 7-globulins 16.0-19.2. The highest glycoprotein content is thus found in a, -, a₂-, and /3-globulins.

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Increased contents of these globulins indicate an active process. The highest increase in the a₂-globulins is observed in acute rheumatic diseases, and of aj-globulins, in long-standing pathologies.

Determination of seromucoid in the blood is informative though not specific for an active rheumatic process. The total amount of seromucoid (which contains several mucoproteins) is determined by the proteinous component (the biuret test). Normally it is 0.75 ± 0.025 g/1. At the present time nine separate proteins are known to compose seromucoids. Hap-toglobin is a seromucoid protein. It is a component part of a₂-globulin and can combine with haemoglobin. The haptoglobin-haemoglobin complex is absorbed by the reticuloendothelial system and prevents loss of iron during destruction of erythrocytes. The normal content of haptoglobin is 1.0 ± 0.032 g/1. In acute phase of collagenosis, the concentration of this protein sharply increases in proportion with the activity and dissemination of the process. This is a more permanent sign than the increased ESR. Quantitative determination of haptoglobin is done by electrophoresis. At the present time several variants of haptoglobin have been discovered but their diagnostic value is unknown.

The determination of ceruloplasmin, the copper-containing glycopro-tein of blood, in rheumatoid patients has a certain diagnostic significance. Ceruloplasmin is an «₂-globulin transporting plasma copper. It is deter­mined in deproteinized serum by paraphenylene diamine. Its normal con­tent is 0.2 ± 0.05 g/1; its content increases in the active phase of inflamma­tion.

The activity of inflammation in collagen diseases is determined not only by concentration of protein components in the blood serum but also by the concentration of the carbohydrate components of glycoproteins: hexoses (D-galactose, D-mannose, D-glucose), pentoses (D-xylose, L-arabinose), desoxy-sugars (L-fucose, L-ramnose) and neuraminic (sialic) acid.

Determination of hexoses. The method is based on a colour reaction of orcinol or resorcinol, with subsequent colorimetry of coloured solutions and determination of concentrations from calibration curves. Normal con­centration of hexoses in healthy individuals is 1.25 ± 0.025 g/1; the hexose level increases in collagen diseases.

Determination of fucose. A product of reaction between glycoprotein and sulphuric acid is mixed with cysteine hydrochloride. Normal fucose concentration is 0.09 ± 0.01 g/1.

Determination of sialic (neuraminic) acids by Hess's method. The reac­tion is based on the formation of a coloured product of sialic acids eliminated from the serum glycoproteins with aceto-sulphuric reagent, and subsequent colorimetry of the coloured solution. Normal concentration of sialic acids is 0.56 ± 0.025 g/1. Their concentration increases during max­imum activity of a rheumatoid process.

Concentration of fibrinogen in the patient's blood can increase during the maximum activity of a pathological process.

C-reactive protein appears in the blood serum of rheumatoid patients. This protein is absent from the blood of healthy individuals. Its name C-reactive protein owes to its ability to precipitate with C-polysaccharide of pneumococcus. During electrophoresis, it moves with a₂-globulins. It is determined by the Anderson and McCarthy method (by precipitation with specifically immune serum). This test is not specific either: C-reactive pro­tein appears in the blood of patients with pneumonia, streptococcal and staphylococcal infections, and in myocardial infarction.

A rheumatoid factor, which is a class M inmmunoglobulin, can be found in the blood of patients with systemic lupus erythematosus and rheumatoid polyarthritis. But it has been recently proved that class G and A immunoglobulins are also present in the blood of these patients and it is therefore more correct to speak about rheumatoid factors. The latex fixa­tion test is used for the purpose. The blood serum is tested by the agglutina­tion reaction with human -y-globulin adsorbed on latex particles. Another method is based on the Waller-Rose reaction, where rabbit 7-globulin is adsorbed on sheep erythrocytes. The results are determined by the max­imum dilution of the serum (titre) at which the rheumatoid factor can be detected. The maximum titre in healthy individuals does not exceed 1: 64. The discovery of the rheumatoid factor is only of relative diagnostic significance, since the factor can be detected also in the presence of some other diseases (hepatitis, syphilis, tuberculosis, tumours).

Blood, bone marrow, and exudate of patients with systemic lupus erythematosus can contain the lupus erythematosus factor (LE phenomenon, lupus erythematosus cells). Because of the presence in the blood serum of the LE factor of the globulin nature, the nuclei of blood and tissue cells swell, the chromatin structure is destroyed and chromatin converts into an amorphous mass. This material is foreign to the body and is therefore destroyed by leucocytes. LE cells are detected microscopically. These are phagocytes (usually neutrophilic leucocytes) whose cytoplasm contains one or several homogeneous red-violet (azure-eosin) formations. Free bodies of the same colour and structure can be seen. LE cells sur­rounded by neutrophils (rosettes) can also be found. LE cells should be dif­ferentiated from neutrophilic leucocytes which have phagocytosed nuclear remnants with preserved contours of the chromatin network. LE cells are detected in high-leucocyte smears stained after Romanovsky. The in­cidence of LE cells in patients with systemic lupus erythematosus varies from 40 to 95 per cent. The LE phenomenon can also be observed (although much less frequently) in patients with grave liver affections, acute leucosis, rheumatism, tuberculosis, certain types of anaemia,

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nodular periarteritis, but the LE cells are not detected permanently in them, and they only occur as single cells.

Antinuclear reactions are now used for diagnostic purposes. Reactions for determination of antibodies to DNA, desoxyribonucleotide, and to cell nuclei are among them. The immunofluorescence method is used for the purpose.

Systemic affections of connective tissue are attended by increased ESR and sometimes by neutrophilic leucocytosis. Leucopenia with shift to the left (to myelocytes) can be seen in patients with systemic lupus erythematosus. Hypo- or normochromic anaemia can be revealed in pa­tients with long-standing and continually relapsing forms of rheumatism, rheumatoid arthritis, and systemic lupus erythematosus.

Increased titres of antistreptococcal antibodies, i.e antistrep-tohyaluronidase and antistreptokinase (more than 1: 300) and antistrep-tolysine (more than 1: 250) are characteristic immunological changes in col­lagen diseases. Increased titres of the antistreptococcal antibodies is a par­ticularly serious factor in the absence of infectious foci in the body, especially so if the titres are very high (1: 1500 and over). The streptococcus antibodies can however sometimes remain at the same level in diseases which otherwise would be attended by their increased level.

at first sight, might have no direct relation to skeletal affections. Systemic scleroderma, for example, is characterized by osteolysis (resorption of bones) of distal phalanges of the fingers and toes, and osteoporosis, mainly epiphyseal one. This sign sometimes helps differentiate this disease from other collagen diseases.

Biopsy

Biopsy is indicated in cases suspected for tumour, for the determination of the character of muscular affections in systemic myopathies and in col­lagen diseases. In systemic lupus erythematosus study of bioptate of the synovial membrane of the joints, liver, and kidneys helps reveal changes typical of a given disease. Lupus nephritis, haematoxylin bodies, and the " wire-loop" phenomenon are especially specific. Biopsy of the synovial membrane of joints, rheumatoid nodes (rheumatoid granuloma) is of great importance for diagnosis of rheumatoid arthritis. Amyloidosis, which is secondary to this main disease, can be revealed by biopsy of the kidney, gum or rectal mucosa. Biopsy of the skin, and in some cases of the lymph nodes, is of great importance for the diagnosis of collagen diseases.

X-RAY EXAMINATION

X-rays reveal calcification of soft tissues, e.g. in systemic scleroderma. But the X-ray examination is most valuable in diagnosis of diseases of bones and joints. Radiographs of bones and joints are usually taken. A new technique known as electroroentgenography is now used by which the picture is taken not on an X-ray film but on special paper. In order to reveal pathological changes, pictures of symmetrical bones and joints are usually made at least in two projections. The analysis of X-ray pictures reveals the proportions of the bones, their shapes, inner structure, and the condition of the joint slit. Osteoporosis (rarefaction of bone tissue), the presence of focal defects of the bones (in tumours, their metastases, etc.), osteosclerosis (consolidation of bone tissue in chronic haematogenic osteomyelitis, etc.), deformities of bones, changes in their articulation (narrowing or dilatation of the joint slit, dislocation, incomplete disloca­tion, etc.) and other pathological conditions can be detected by X-rays.

Each disease is characterized by a certain X-ray picture of changes in bones and joints. It should be remembered that bones are also affected in some endocrine diseases (hyperparathyroidism, acromegaly), prolonged treatment with glucocorticosteroids (osteoporosis develops), in the last term of pregnancy, in metabolic disorders, and in many other cases which,