α ₁ -Antitrypsin A serum glycoprotein inhibiting proteolytic enzymes, such as trypsin, chymotrypsin and elastase. It also acts as an acute phase protein. Its serum level rises in inflammatory diseases. The coding gene is located on the 14th chromosome, where it can occur in form of 25 alleles. Some of them code for physiological products (PiMM phenotype), whilst others are related to pathological states, e.g. PiZZ phenotype, which is often associated with emphysema, cirrhosis and cholelithiasis, where its serum levels are diminished (α₁-antitrypsin deficiency).

α ₁ -Microglobulin (α ₁ M) A protein synthesised in the liver and present in blood, serum and urine. Complexes of α₁M with monomeric immunoglobulin A (IgA) participate in renal IgA nephropathy where the serum level of α₂M is also usually increased.

α ₂ -Macroglobulin (α ₂ M) A serum glycoprotein working as inhibitor of a number of proteases including thrombin, plasmin, kallikrein, trypsin, chymotrypsin, elastase, collagenase and cathepsin B and G. α₂M is produced mainly by macrophages and regulates the proteolytic balance in a number of extracellular processes that exert their action mainly in blood coagulation, fibrinolysis and inflammation. α₂M and protease complexes are proteolytically inactive and are eliminated quickly (in minutes) from the circulation. Its serum levels are increased especially in nephrotic syndrome, atopic dermatitis, diabetes mellitus and ataxia– telangiectasia.

Abatacept Abatacept (Orencia^®) is an injectable, synthetic (man-made) soluble fusion protein that consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to the modified Fc portion of human immunoglobulin G1 (IgG1). Abatacept is produced by recombinant DNA technology in a mammalian cell expression system.

Abatacept belongs to a class of drugs called co-stimulation modulators, shown to inhibit T cell activation by binding to CD80 and CD86, thereby blocking interaction with CD28. Blockade of this interaction has been shown to inhibit the autoimmune T-cell activation that has been implicated in the pathogenesis of rheumatoid arthritis. Abatacept attaches to a protein on the surface of T lymphocytes and blocks both the production of new T lymphocytes and the production of the chemicals that destroy tissue and cause the symptoms and signs of arthritis. Abatacept slows the damage to joints and cartilage and relieves the symptoms and signs of arthritis.

Abatacept is indicated for adult rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) and may be used as monotherapy or concomitantly with DMARDs other than TNF antagonists. Abatacept is distributed for intravenous as well as for subcutaneous application. Intravenously abatacept is infused over 30 min. The initial dose of abatacept is followed by doses 2 and 4 weeks later with further doses every 4 weeks thereafter. Adults weighing <60 kg should receive a 500 mg dose, weighing 60–100 kg a 750 mg dose and weighing >100 kg a 1000 mg dose. Paediatric patients weighing less than 75 kg receive 10 mg/kg intravenously based on the patient’s body weight. Paediatric patients weighing 75 kg or more should be administered abatacept following the adult intravenous dosing regimen, not to exceed a maximum dose of 1000 mg.

The solution for subcutaneous injection is only for the use in rheumatoid arthritis. If the patient is taking Orencia for the first time, the infusion with a single iv loading dose of approximately 10 mg/kg bodyweight should be used for the first administration, followed by an injection under the skin the next day and then weekly. The self-injectable formulation is a fixed 125 mg dose.

The most common side effects of abatacept include: back pain, cough, dizziness, headache, high blood pressure, nausea, rash, upper respiratory tract infection and urinary tract infection. Administration of abatacept in patients with chronic obstructive pulmonary disease (COPD) has been associated with exacerbation and increased incidence of COPD symptoms. Patients suffering from both rheumatoid arthritis and COPD who elect to have abatacept therapy should monitor symptoms carefully and in collaboration with their physicians. Concurrent administration of a TNF inhibitor with abatacept has been associated with an increased risk of serious infections and no significant additional efficacy over the use of the TNF antagonists alone. It is recommended not to give live vaccines concurrently with abatacept or within 3 months of its discontinuation as it might blunt the effectiveness of some immunisations. The long-term effects of abatacept with remission of both clinical symptoms and radiographic joint damage have been demonstrated in several trials.

HIV infects cells that possess differential antigen CD4⁺ on their surface (particularly T lymphocytes and macrophages). Non-specific symptoms occur at an early stage after infection. Subfebrile temperatures, weakness, sweating, arthralgias, myalgia, headache, diarrhoea, lymphadenopathy and also certain neurological symptoms may occur. Such symptoms last for several days to 2 weeks. In the majority of infected individuals, these symptoms may not be apparent. Approximately 2 weeks after virus transmission, the viral antigens (p24, gp41) can be detected in the blood of the infected individual. Later on these antigens disappear and antibodies against certain HIV antigens (anti-p24 and anti-gp41) can be detected in the blood of the infected individual at 2–3 months, which is diagnostic confirmation of infection. The disease now often enters a latent period without any clinical symptoms, except for possible lymphadenopathy. Such a period may last up to 12 years, and it terminates by activation of the disease, which, in untreated cases, leads to death in 6–30 months.

Activation of the disease is manifested by decreasing antibodies against the HIV antigens (anti-p24) and concurrent reoccurrence of these antigens in the blood. Such an event is referred to as seroconversion. The number of T lymphocytes in peripheral blood decreases. If the number of T lymphocytes is less the 0.2 × 10⁹/l, then the infected individual is considered to have severe AIDS, even though the patient may be asymptomatic. AIDS symptoms include infections due to normal, non-pathogenic microorganisms (pneumonia due to Pneumocystis carinii – in 50 % of all patients) and certain malignancies with rapid course (Kaposi sarcoma – approximately 1/3 of all patients). Dementia and changes of psychomotor functions, which are very likely due to direct HIV infection of glial cells in the brain, occur in approximately 2/3 of all patients. The typical clinical picture of AIDS does not develop in certain patients; however, these patients suffer from a group of symptoms referred to as ARC (AIDS-related complex) in which infections and tumours are not present. ARC may or may not progress to full-blown AIDS.

The diagnosis of AIDS consists of serological assessment, immunological assessment (determination of CD4⁺ lymphocytes or the CD4⁺/CD8⁺ ratio in peripheral blood), clinical assessment and relevant medical history. Contemporary treatment is only partial, and generally it allows inhibition of HIV replication in infected cells (azidothymidine, zidovudine) and thereby prolongs the period free of any clinical symptoms. However, after development of the symptoms, treatment cannot cure the disease.

The patient should be immediately admitted to hospital (orthopaedic, rheumatology, neurosurgery or traumatology departments).

The patient should be admitted to the department of internal medicine or neurology, which have experiences with the treatment of the disease.

Treatment complications

Treatment complications can include hypokalemia, which may often occur after administration of glucocorticoids and may cause heart rhythm problems or acute muscle weakness. Potassium should be administered.

Adrenal insufficiency often arises when glucocorticoids are administered or when their administration is interrupted, sometimes even if it is not reduced; however, in some conditions (intercurrent illness, stress conditions), the endogenous need increased. It is necessary to increase the dose of glucocorticoids and, where appropriate, to admit the patient to the hospital.

When applying a local anaesthetic intradurally, the patient must be admitted to the intensive care unit.

Perineurial injection may cause transient paresis or hypoesthesia. Bed rest is indicated, until the effect of the anaesthetic vanishes.

Acute febrile neutrophilic dermatosis (Sweet’s syndrome) A rare disease of unknown aetiology characterised by marked inflammatory neutrophilic skin infiltrates.

Acute prolapse of cervical intervertebral disc Protrusion of the intervertebral disc with intact annulus fibrosus and prolapse of the intervertebral disc with nucleus pulposus prolapse through the perforated annulus fibrosus are the consequence of degenerative changes in intervertebral disc tissues. Prolapse of the disc is usually directed posteriorly through a weak dorsal longitudinal ligament.

Acute shoulder pain without movement limitation may be caused by radicular syndrome of C5, herpes zoster (shingles), diseases of the bones around the shoulder, Paget–Schroetter syndrome and subclavian, axillary or brachial vein thrombophlebitis leading to livid oedema of the hand.

Limitation of active movement (passive movements are unlimited) is caused by complete disruption of the rotator cuff usually following trauma, overload, mechanical friction or trauma to the rotator tendons with break up or rupture. Commonly the supraspinatus muscle tendon is affected. In the case of complete rupture, active abduction to the extent of 0–30° is impossible, and the anterior tip of the acromion is tender upon palpation. Sooner or later, the supraspinatus muscle atrophies. In some cases, the X-ray shows calcification in the supraspinatus muscle tendon. Ultrasound or magnetic resonance imaging can confirm disruption of the tendon.

Adalimumab Adalimumab (Humira^®) is a recombinant human IgG1 monoclonal antibody specific for human tumour necrosis factor (TNF). Adalimumab binds specifically to TNF-alpha and blocks its interaction with the p55 and p75 cell surface TNF receptors. Adalimumab does not bind or inactivate lymphotoxin (TNF-beta). Adalimumab was first approved by FDA in December 2002 for reducing signs and symptoms and inhibiting the progression of structural damage in adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs). Adalimumab can be used alone or in combination with methotrexate (MTX) or other DMARDs. Adalimumab has also been approved for moderate to severe polyarticular juvenile idiopathic arthritis (JIA) in children 4 years of age and older, psoriatic arthritis (PsA) in adults and in ankylosing spondylitis (AS) in adults. Besides these indications in rheumatic diseases, adalimumab has approvement to treat moderate to severe Crohn’s disease (CD) in adults, moderate to severe Crohn’s disease (CD) in children 6 years and older, moderate to severe ulcerative colitis (UC) and moderate to severe chronic plaque psoriasis (Ps) in adults. Adalimumab 40 mg is administered using a prefilled ready to use syringe or pen by subcutaneous injection once every other week.

Agammaglobulinaemia A condition in which the total serum immunoglobulin level in the individual is lower than 1 g/L (immunodeficiency). It is caused by genetically conditioned insufficient production of immunoglobulins. There are two forms: Bruton’s or Swiss type. Bruton’s type is congenital, sex-linked agammaglobulinaemia in boys. The clinical picture is dominated by pyogenic infections. No antibodies are produced after vaccination.

The Swiss type of idiopathic agammaglobulinaemia with lymphopenia is a severe combined immunodeficiency (SCID). The clinical picture is dominated by systemic fungal infections, mainly candidiasis, together with bacterial infections such as in Bruton’s type. The mere repletion of immunoglobulins is rarely therapeutically successful, so bone marrow transplantation should be considered (immunoglobulin deficiency).

Algodystrophic syndrome (ADS) ADS is characterised as a complex of symptoms elicited by a nociceptive stimulus.

It is often a post-traumatic condition which develops after pulling, dislocation, fracture, wrong plastering or nerve interruption.

It is a neurogenic inflammation causing pain with the substance P being excreted in pain-sensitive receptors.

At the same time, a slight synovitis develops, in association with modified microcirculation in the bone and periarticular tissue.

At acute stage, the arm, leg or affected joint and surrounding areas are red or purple, swollen, warm and sensitive to pressure or moving, and the patient experiences a burning sensation. At subacute stage, the joint or the relevant part of the body is wet, cold, having white or purple colour.

At chronic stage, a periarticular fibrosis develops, with thickened skin and subcutaneous tissue and with contracture of the joints. A special case is the hand–arm syndrome, which causes arm contracture with diffuse swelling of the hand and fingers. Besides trauma, it often develops in a reflexive manner following infarction and strokes.

Laboratory anomalies are not present; sedimentation is normal.

Radiological signs. At the initial stage of the disease, the isotopic examination detects accumulation of the pharmaceutical agent. Later, characteristic spotty bone atrophy develops which at the third stage turns into a hypertrophic atrophy with thickening of certain trabeculae.

Therapy. At first, bed rest, analgesics, beta-blockers, vasodilators and sympatholytic agents (also intra-arterial) or regional sympathetic blockers are indicated. To improve circulation, calcium channel blockers, glucocorticoids per os and blood vessel massage (vasotrain) may be administered, followed by step-by-step mobilisation, loading. At the chronic stage, intensive mobilisation, thermotherapy and ultrasound are indicated.

Algometry (evaluation of pain threshold)

The evaluation of pain is an integral part of each evaluation system in rheumatology, e.g. HAQ, RADAI, WOMAC, Lequesne index, AIMS and others.

Alkaptonuria and ochronosis Alkaptonuria is a rare inborn (autosomal recessive) error of the metabolism of aromatic amino acids phenylalanine and tyrosine where, due to a defective activity of the enzyme called homogentisic acid oxidase, there is no cleavage of homogentisic acid (alkapton) causing accumulation in the body and excretion in urine. Its polymer – ochronotic pigment – impregnates the bradytrophic tissues.