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Chapter 1,2 Chapter 3,4,5 Chapter 6,7,8 Chapter 9,10

Prof. Abdel-Samad El-Hewala

Professor of Rheumatology & Rehabilitation

Faculty of Medicine

Zagazig University

Chapter 3

CLASSIFICATION OF RHEUMATIC DISEASES

More than 100 rheumatologic entities are now recognized. In general, they are broadly classified as:

1- Degenerative Joint Disease:

This is very common, about 75% of the population by the age of 60-65 will have osteoarthrosis. It may be:

(a) Primary -----> where the cause is unknown,

(b) Secondary to a well known cause.

2- Polyarthritis of Unknown Aetiology:

a) Rheumatoid arthritis :-

Chronic (possibly remittent or episodic) pain, swelling and impairment of function affecting several or numerous small joints (but not the distal interphlanageal joints of the fingers) and large joints as well as tendon sheaths.

b) Still's disease :-

Juvenile chronic polyarthritis with lymphadenopathy and leucocytosis.

c) Ankylosing spondylids :-

"Deep-seated" pain- already present for some considerable time and usually occurring during the early hours of morning. Low down in the back (referable to the sacro-iliac joints and lumbosacral joint), stiffening of the spine.

d) Psoriatic arthritis :-

Chronic (possibly remittent or episodic) pain swelling and impairment of function affecting several small joints and large joints; usually associated with psoriasis, either in the patient himself (sometimes psoriasis may be absent or appear later) or in close relatives.

e) Reiter's syndrome :- (urethro-conjunctivo-synovial syndrome)

Arthritis, urethritis and conjunctivitis- though the triad does not need to be complete, frequently preceded by an infection of the gut (usually

desentry) or of the urinary tract. Additional findings: balanitis, keratoderma, glossitis and painless ulcerative stomatitis. Encountered chiefly in young men.

3- Connective Tissue Disorders:

a) Systemic Lupus Erythematosus :-

The symptomatology of this disease includes: polyarthritis or arthralgia, fever, loss of hair, as well as a wide variety of skin lesions disorders affecting internal organs such as the kidneys, lungs, heart, serous membranes (Pleurisy, pericarditis, peritonitis) and the central nervous system.

b) Scleroderma (progressive systemic sclerosis) :-

Chronic, progressive atrophy and induration of the skin (after an initial oedematous stage), accompanied by disappearance of the normal n creases, loss of function in the ringers, hands and rigidity of the facial expression, internal organs are sometimes involved and sometimes not.

4- Rheumatic Fever:

Onset of polyarthritis, affecting large joints fleating in character, come 2-4 weeks after a streptococcal infection, usually accompanied by -e throat, and frequently also carditis.

5- Metabolic Arthritis:

a) Gouty arthritis :-

Onset, within only a few hours, of attacks lasting 5-7 days and characterised by severe pain, swelling, and reddening confined to one joint only.

b) Pseudogout (chondrocalcinosis)

6- Non-articular Rheumatism:

a) Polymyalgia rheumatica:

Muscle pain in the shoulder girdle and upper arms and/or in the pelvic girdle and thighs in patients over 50 years of age. These pains occasionally develop slowly over the course of several weeks; and associated with general symptoms.

b) Diseases of the muscles, tendons and ligaments:

They are due to mechanical or degenerative causes.

c) Scapulo-humeral (shoulder) periarthritis:

Pain, tenderness and impairment of function in the shoulder region, primarily due to a combination of pathological processes in the periarticular tissues (tendons, tendon sheaths, bursae, ligaments and muscles) and in the joint capsule.

7- Arthritis with known Infectious Agent:

a) Septic arthritis

b) Tuberculous arthritis

Joint infection is usually blood borne but may occur via penetrating wounds or by spread from contiguous bone.

8- Diseases of the spine due to degenerative or static strain:

Pain of insidious or acute onset, associated with impairment of junction affecting individual segments of the vertebral column, with muscle spasm, and occasionally radiating peripherally. Severity of symptoms clearly dependent upon posture, movement and exercise.

9- Primary Osteoporosis:

Diffuse pain in the spine (but with no radicular symptoms) which is aggravated in response to jolting or jarring; persistent pain at night, noticeable decrease in stature, and changes in posture.

10- Traumatic and / or Neurogenic Disorders:

a) Carpal tunnel syndrome (compression neuropathy of the median nerve):-

Painful paraesthsiae in the hand, occurring especially at night and radiating into the thumb and fingers (except the little finger), as well as proximally up the flexor aspect of the forearm, often bilateral.

b) Charcot joint: -

Painless arthropathy in cases of absent deep and superficial sensation.

This section will cover those infectious diseases that cause arthritis by the direct invasion of the micro-organisms into the joint. The infectious agent may be a bacterium, a virus or a fungus.

Commonest organisms include staphylococcus, pneumococcus, gonococcus and haemophilus influenza. An infectious agent may cause arthritis by a number of mechanisms:

The organisms first settle and replicate in the synovial membrane which shows a pyogenic inflammation, proteolytic enzymes are continuously released causing further inflammation. It becomes red, swollen and an exudate forms.

Eventually, synovial lining cells regenerates and hyperplasia with chronic inflammation and granulation tissue which occur if the infection is untreated, cartilage erosions and finally articular cartilage destruction with fibrous or bony ankylosis will develop.

Septic arthritis may appear do novo, or may follow evidence of infection elsewhere, predisposing factors include previous damage to the joint by disease or trauma, including operation or intra-articular injection, debilitating illness especially diabetes and treatment with corticosteroids or with cytotoxic agents.

Usually there is an acutely painful monoarthritis with a swinging temperature, rigors. The knees, elbows, wrists or hips are commonly affected although no joint is immune. Whenever an infection is suspected, the joint should be drained under sterile conditions, a portion of the synovial fluids is cultured and a gram stain smear immediately performed. Helpful diagnostic clues obtained from synovial fluid analysis include a marked leucocytosis (> 50000 / mm3), with greater than 80% polymorphnuclear leucocytes and a synovial fluid glucose depressed in relation to the blood glucose. A peripheral blood leucocytosis and an elevated erythrocyte sedimentation rate are usually present, but are not specific.

xAcute osteomyelitis (adjacent joint may be painful and slightly swollen due to synovial reaction. However, maximum tenderness is over involved bone rather than joint).

yAcute septic arthritis in infants: differentiate acute septicaemia, battered baby syndrome scurvy (painful subperiosteal haemorrhages).

a.Generally, antibiotics are initiated parenterally, often in large doses, when bacterial arthritis is suspected, the duration of therapy ranges between 2-4 weeks depending on the clincial response.

b.Arthrocentesis (joint drainage) is always required as often as fluid reaccumulates. Certain circumstances will necessitate open surgical drainage. These include hip or shoulder joint infections and when purulent accumulations or loculations cannot be adequately drained, joint drainage should be continued until there is no further accumulation of purulent synovial fluid.

c.In the early stages of the infection, immobilization with splints or occasionally with traction may be needed to help control pain, but static exercises should be begun quickly to prevent severe muscle atrophy. Allow weight bearing only when active inflammation has subsided. Later, mobilizing and progressive resistance exercises.

Chapter 5

RHEUMATOID ARTHRITIS

Definition:

Rheumatoid arthritis (R.A.) in its fully developed form is a peripheral symmetrical inflammatory disease of the synovium that leads to destructive changes in the joints, with presence of abnormal antibodies (Rheumatoid factors) in the blood. Although arthritis is the most frequent manifestation, it must be remembered that this is a generalized disease involving many systems so that it can be more correctly termed rheumatoid disease.

Incidence:

R.A. occurs in about 1-2% of adult population. It is the most common connective tissue disease and certainly the most important in socio economic terms. Females are more commonly affected than males in a ratio of 3:1. It may occur at any age from 16-70 years, but the maximum age of incidence is from 30-55 years.

Aetiology:

The cause of R.A. remains unknown, speculative theories suggest that initiating factors either infective or traumatic may initiate a situation evoking an immune reaction within the joint, which then becomes preserved and self perpetuating.

A-Initiating factors:

(1) Autoimmunity: The present knowledge denotes that R.A. is the disease with alter immune reaction (autoimmune disease). Autoantibodies (anti-IgG) are produced against normal IgG of self. Rheumatoid factor is one antibody against IgG.

Evidence of immune over activity includes:

a.The presence of an immunoglobulin (Rheumatoid factor) in the blood, lymph nodes and synovial membrane of rheumatoid patients.

b.The presence of immune complex particles within cells of the rheumatoid synovial fluid.

c.Infiltration of synovial membrane by lymphocytes and plasma cells.

d.The finding of lowered complement levels in synovial fluid of rheumatoid joints.

(2) Faulty IgG: antibody produced against abnormal IgG.

(3) Unidentified antigens: e.g. for mycoplasma. colstridium perfringens, bacterial cell wall antigens, viral e.g. Epstein-Barr virus, Rubella virus.

B- Modifying Factors:

(1) Hereditary: Higher prevalence of seropositive R.A. in first-degree relatives than in controls. Concordance in monozygotic twins is significantly higher than in dizygotic twins. No association with HLA-B locus but:-

a. strong association with HLA. D R4.

b. Seropositive erosive disease more likely in HLA- DR.3 patients.

(2) Climate: R.A. is equally common in hot dry as in cold wet climates, but symptoms are more frequent in the latter.

(3) Trauma: Onset often coincides with trauma to joint, and injured joints often affected more severely than others.

(4) Endocrine: While no known endocrine abnormality consistently occurs in R.A, the following facts are of importance:

Higher incidence in females, Incidence is lower in takers of the contraceptive pills. Remissions are common in pregnancy. Adrenocortical steroids and ACTH produce marked decrease in disease activity. However, there is no constant abnormality of adrenocortical activity in R.A. .R.A. is uncommon in association with hyperthyroidism and exacerbation of disease may occur after thyroidectomy.

(5) Psychological: Onset of R.A. is frequently associated with mental trauma (e.g. death of a relative).

(6) Liver disease: Remission of R.A. are common in obstructive or intrahepatic jaundice, possibly due to delay in cortisol breakdown by liver, giving high levels of plasma cortisol.

Pathogenesis: Immunological changes in synovium result in:

(a)Inflammatory response: mediated by immune complexes (antigen + antibody + complement) which induce polymorph phagocytosis with rupture of these polymorphs (phagocytes) and release of lysosomal enzymes and proteases which act as the chemical mediator of inflammation.

(b)Tissue damage: synovial membrane is thus injured and inflamed. Activated macrophages in membrane release interleukin.I, which stimulates fibroblasts to secrete prostaglandins and proteases damaging synovium, cartilage and bone. Hyperplasia of synovial cells produces pannus, which releases damaging chemicals into synovial fluid so eroding cartilage and eventually bone.

Pathology:

A- Pathology of Joints:

(1)Synovial membranes: No synovial tissue is exempt from involvement, hence the lining of tendon sheaths and bursae may be involved. The synovial membrane is oedematous, congested, thick and proliferates to form villi filling joint space. At junction of synovium with articular cartilage, synovial pannus (granulation tissue) spreads on the articular cartilage so that the normally glistening white surface becomes covered with granulation tissue. The synovial pannus causes erosions of surface of articular cartilage & by bearching the cortex at the cartilage/synovium junctions, it erodes the subchondrial bone. The erosions may become large & cystic. Later, pannus organizes forming thick fibrous tissue (leading to fibrous ankylosis).

(2)Articular cartilage: The articular surface becomes rough and loses its normally glistening white surface. Cartilage is eroded by granulation tissue, with focal necrosis and thinning occurs due to erosion by proteolytic enzymes and collagenases from pannus.

(3)Joint capsule: Thickened, due to oedema and (in late stages) fibrosis.

(4)Juxta-articular bone: Osteoporosis occurs early in rheumatoid disease.

Granulation tissue formed in bone marrow spaces and late fibrous tissue which extends into joint and joins with organizing pannus forming fibrous ankylosis.

B- Extra articular pathology:

(1)Subcutaneous nodules: usually occur in the pressure areas, commonly on the subcutaneous ulnar border of the forearm, develop in about 25% of patients. They are nearly always associated with seropositivity. They are of variable size, it is a non-capsulated, may be attached to bone. They are painless.

It has a characteristic histological pattern, with three well-marked zones:

Central zone: fibrinoid degeneration and necrosis.

Middle zone: fibroblasts arranged in radial palisading.

Outer zone: fibrous tissue with infiltration of chronic inflammatory cells (lymphocytes and plasma cells).

(2)Vasculitis: Arteritis occurs in rheumatoid disease, it is of 3 categories:

a- Involvement of small end arteries in the nail folds producing characteristic minute ischaemic areas.

b- Involvement of medium-sized arteries such as the vasa nervosa and digital arteries.

c- Involvement of large arterial trunk e.g. mesenteric or major limb vessels.

(3)Muscle lesions: Muscle wasting is common in R.A. This is most pronounced in muscles acting on inflamed joints. This may be due to:

- Lymphocytic infiltration of the muscle

- Secondary to nerve lesion

- Secondary to cortices teroid treatment especially triamcinolone.

- Myopathy-----> Electromyography shows myopathic changes in a proportion of cases of advanced R.A.

(4)Nerve lesions: either mononeuritis as entrapment neuropathy (Carpal tunnel syndrome) or poly-neuropathy in cases of vasculitis.

(5)Tendon lesions: Thickening, fibrinoid degeneration, and fibrosis of tendon sheaths may for example, result in trigger finger (due to adhesions between long flexor tendon to its sheath) or attrition rupture consequent upon degeneration in finger extensor tendons passing over ulnar styloid process.

(6)Lymph nodes: Enlargement in 30% of cases and in Felty's syndrome is associated with splenomegaly and leucopenia.

Clinical features:

Onset of Diseases: The onset is very variable, it may be acute or insidious, monoarticular or polyarticular, i.e.

uTypical onset: Gradual development of symmetrical polyarthritis involves small joints of hands and feet.

vAcute polyarthritis: may be associated with fever, sweating and leucocytosis

wAcute monoarthritis: sudden painful swelling of a large joint.

xChronic monoarthritis: Insidious painful swelling of a large joint e.g. knee.

yOnset with soft-tissue lesion: R.A. may be heralded by tenosynovitis "trigger-finger", rotator cuff lesion; or carpal tunnel syndrome.

zPalindromic (episodic): Rheumatism: which is characterized by short-lived episodes of pain with periods of complete remission later this often evolves into more obvious R.A.

1. Articular manifestations:

Symptoms: Pain and stiffness of the joints are the outstanding complaints. In the mildly inflamed joint, pain appears only on movement, whereas with increasing disease activity there is spontaneous pain at rest, too.

Morning stiffness: Severe painful stiffness that is present on awaking in the morning and wears off gradually during the day with activity. This symptom is the hallmark of inflammatory arthropathy. Morning stiffness should last more than half an hour to be accepted as significant.

Pattern of Joint Involvement: Most commonly affected joints are the MCP, PIP and the lateral four MTP joints. Following these come the wrist, knees, shoulders, elbows, hips, ankles, cervical spine and temporo-mandibular joints.

Rheumatoid involvement in the cervical spine is usually confined to the C 1-4 segments with the brunt of the inflammatory process falling on the atlanto-axial joint.

Signs:

uSynovial hypertrophy and effusion produce the typical swelling of fingers.

- Fingers -----> spindle-shaped appearance swelling of MCP

- Wrist -------> dorsum of the hand (swelling).

- Knee -------> horseshoe swelling above and beside the patella.

vSubluxation and Instability:

Progressive joint destruction by erosive change leads not only to limitation of movement but, in certain joints, to subluxation.

wRegional joint deformity and functional disability:

Hands:

a)Ulnar deviation: At MCP joints (Figure 6). Usually associated with anterior subluxation of metacarpals on proximal phalanges and dislocation of extensor tendons medially. This deformity is due to laxity of radial collateral ligaments, slipping of extensor tendons to ulnar side, radial carpal rotation and pull of abductor digiti minimi.

(b)Swan-neck deformity: Hyperextension of PIP & flexion of DIP (Figure 7).

(c)Boutonniere deformity: Flexion of PIP and extension of DIP (Figure 8).

(d)Thumbs -----> Flexion of MCP, hyperextension of PIP -----> Z-shaped deformity (Figure 7).

(e)Tendon lesions: Trigger finger -----> due to tenosynovitis of flexor tendon. Inability to extend finger, at MCP joints due to extensor tendon ruptures, usually occurring at ulnar styloid process.

Wrist: Loss of movement, finally fibrous ankylosis may occur. Prominent tender ulnar styloid process with pain on pronation/ supination. Piano sign.

Knees: Baker's cyst (cystic swelling in popliteal fossa). Flexion or valgus defomity and instability may occur later.

Nail-fold vasculitis

Ulnar deviation

Muscle Wasting

Fig. (6) Ulnar deviation at MCP joints in R.A.

Z-thumb deformity

Swan neck deformity

Boutonniere deformity

Fig. (7) Finger deformities in R. A.

Feet: Tender, prominent, metatarsal heads with 2^ry corns; lateral deviation and overriding of toes with pressure sores.

Cervical spine: Atlanto-axial subluxation present in 30 percent of hospital cases causing pain and very' rarely spinal cord compression or vertebral artery occlusion, crico-arytenoid joint involvement causes hoarseness, stridor, dyspnoea, dysphagia and recurrent bronchitis, sedatives are dangerous, tracheostomy occasionally required.

Coarse:

uEpisodic (25 percent): average patient of this type has the attacks of arthritis, one every 2 years (very variable, may be up to 15 years), each lasting about 6 months. This group merges with palindromic rheumatism in which the attacks are much shorter. Many cases eventually develop persistent arthritis.

vPersistent: chronic arthritis with partial remissions and exacerbations. The monoarticular type remains monoarticular in 60 percent. The other 40 percent develop polyarthritis in up to 10 years. Individual joint once involved usually remain involved, though activity fluctuates in this stage resemble advanced osteoarthritic joints. Ultimately 50% of patients have little or no disability; 40% have some disability and 10% are completely disabled.

2. Extra-articular manifestations:

(1) Fever and weight loss:

Active RA, being a systemic disease, is accompanied by the usual manifestations of any inflammatory condition, low grade fever, Anorexia, weight loss, muscle wasting more marked in muscles acting on inflamed joints.

(2) Peri-articular soft tissues:

a.Nodules (25%) usually below elbow but almost any where else.

b.Tenosynovitis around hands or wrists (65%) causing pain, local swelling, tenderness, trigger finger, dysfunction and flexion deformity.

c.Bursitis (common), particularly olecranon causes swelling and discomfort.

d.Synovial cysts appear around any joint but particularly posterior to the knee (Baker's cyst) raised pressure in knees with large effusions forces fluid into the cyst may also cause joint rupture with calf pain, ankle oedema and positive Hofman's sign resembling deep venous thrombosis.

f.Ligamentous laxity leads to hypermobility and deformities, particularly important in ulnar deviation and atlanto-axial subluxation.

b.leg ulcers (rarely), due to trauma (specially in patients on steroids), hypostasis or associated with vasculitis and Felty's syndrome.

a. Scleritis, episcleritis and scleromalcia perforans rare, but may lead to loss of vision.

b. Sjogren's syndrome (15 percent) dry eyes and mouth, confirm by Schirmer's test or rose bengal staining, associated with high incidence of allergic reaction, hyperglobulinaemia, auto-antibodies.

a.Granulomatous lesions in myocardium and valves (rarely cause heart failure), valve lesions (particularly aortic incompetence) & mural thrombi with embolism.

a.Compression carpal tunnel syndrome (50%) shortly before or after onset of arthritis.

b.Pleural effusion; 8% of men may be the presenting feature of rheumatoid arthritis. Fluid may have low glucose, positive latex test of "rheumatoid" cells suggestive but not diagnostic.

d.Caplan's syndrome (multiple pulmonary nodules on chest X-ray in coal workers).

Common and proportional to disease activity multiple causation include failure of bone marrow iron utilization (anaemia of infection) and aspirin, Felty's syndrome, splenomegaly and leucopenia; infections common.

Joints commonest site; staphylococcus aureus commonest organism, may be silent, and not always accompanied by fever or leucocytosis

Aggravated by steroid therapy; important cause of sudden worsening of pain in one joint.

-In early cases, tests for R.F. are usually negative, whereas later they often yield positive findings (Latex test positive in 80%, Rose-waller in 60 %).

-Synovial fluid (examination of which is important in doubtful cases): yellow to greenish and somewhat turbid; slight mucin precipitate; viscosity diminished; leucocytes > 5,000 / cmm., add posphatase and lactic dehydrogenase elevated; rheumatoid factor possible positive.

3-Periostitis: Periosteal reaction in phalanges adjacent to active joints appears in early stages, becoming resorbed later.

4-Erosions: Two types----> surface erosions, usually at articular margins subarticular cysts----> probably due to forcing of synovial fluid under pressure through defective cartilage Later stages:

Very variable. It is still impossible to predict the outcome of a case of R.A. with any degree of certainty. Approximately 40% of cases do very well. 50% have persistent activity with remissions and exacerbations, with some deformity.