Medicinal arthropathy is a collective concept that includes a large group of diseases caused by joint damage when taking medications. It is clinically manifested by joint pain, local redness of the skin, swelling of the periarticular tissues, synovial effusion, difficulty in movement. Pathology is diagnosed mainly on the basis of symptoms and anamnestic data. In some cases, laboratory and instrumental research methods help in making a diagnosis. For treatment, it is necessary to cancel the drug that caused arthropathy, and search for its alternative, as well as symptomatic therapy.
Medicinal arthropathy is a number of diseases characterized by joint damage caused by taking medications (drugs). This pathology belongs to one of the most frequent manifestations of drug disease and includes allergic arthritis, toxic and side effects of drugs, joint damage during hemodialysis and complications of intra-articular administration of drugs. Some individual medicinal arthropathies are specific to a certain gender and age. For example, medicinal lupus is more common in men, and microcrystalline arthritis and aseptic necrosis of the femoral head (ANFH) – in women. Quinolone arthropathy is common among adolescent children.
Long-term use of drugs and the presence of chronic diseases predispose to drug arthropathy. For example, an allergy to animals or plant pollen increases the likelihood of allergic arthritis several times. The immediate causes of arthropathy of medicinal genesis are as follows:
- Allergic reactions. The most common cause of drug damage to the joints. Taking drugs with pronounced allergenic properties (antibiotics, analgesics, etc.) can provoke inflammatory processes in the joints.
- Toxic effect of drugs. Certain drugs (for example, anti-tuberculosis antibiotics) can damage joints due to deterioration of microcirculation, inhibition of the formation of structural elements of cartilage or damage to autonomic nerve fibers innervating joints.
- Violation of metabolic processes. Medicinal arthropathy also develops when using drugs that cause shifts in the exchange of endogenous organic compounds (for example, acceleration of the formation and slowing of uric acid excretion), which leads to the deposition of crystals or salts on the surface of joints and tendons.
- Hemodialysis. In patients with end-stage chronic renal failure who are on dialysis therapy, the excretion of calcium salts is reduced. As a result, these salts are deposited on the tendons and synovial membrane of the joints in the form of calcium hydroxyapatite.
- Intraarticular injection of drugs. Bacterial contamination of the joint cavity is possible if the rules of asepsis and antiseptics are not followed during intra-articular injection of drugs.
Some arthropathies are directly related to a certain drug or pharmacological group. For example, quinolone arthropathy, aseptic osteonecrosis develop with glucocorticosteroid therapy, analgesic arthropathy – with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), shoulder-arm syndrome – with the use of anti-tuberculosis drugs.
The mechanism of the pathological effect of drugs on the joints is different. In allergic arthritis, joint damage occurs due to allergic inflammation – the deposition of allergen-antibody complexes, the release of histamine, serotonin, leukotrienes from mast cells, and lymphocytic infiltration. When nucleotide breakdown is activated and uric acid secretion is inhibited in the distal tubules of the kidneys, its crystals are deposited in the joints (medicinal gout). Damage to the sympathetic nerves by antituberculous drugs disrupts the nervous trophism of the joints and muscles of the upper extremities. Drugs such as hydrazaline and apressin are able to stimulate the production of antibodies to cell nuclei and nuclear components, thereby simulating systemic lupus erythematosus (drug lupus syndrome). Some medications cause an exacerbation of an already existing inflammatory joint disease (rheumatoid arthritis).
Depending on the clinical manifestations, pathogenetic mechanism, as well as on the drug that caused joint damage, the following forms of medicinal arthropathy are distinguished:
Allergic arthritis. The most common form of medicinal arthropathy. Develops with the use of penicillin antibiotics, heparin, insulin, barbiturates, analgin.
Microcrystalline arthritis. Occur due to the deposition of salts or crystals of various compounds in joints and periarticular tissues:
- Medicinal gout. It is caused by taking drugs that violate purine metabolism – pancreatin, cyanocobalamin, nicotinic acid, cytostatics, diuretics, salicylates.
- Pyrophosphate arthropathy. Drugs that contribute to the deposition of calcium pyrophosphate in the joints are thyroid hormones, calcium citrate and sodium.
- Hydroxyapatite arthropathy. In this form, calcification of joints and tendons occurs. It is caused by prolonged intake of vitamin D, ascorbic acid, hemodialysis sessions.
Joint damage in the framework of drug lupus syndrome. There are many drugs that can induce the development of medicinal lupus – apressin, hydralazine, carbamazepine, D-penicillamine, methyldopa, novocainamide, minocycline, sulfasalazine. Unlike SLE, medicinal lupus develops more often in men.
Complications of long-term treatment with glucocorticoids. These include steroid pseudorheumatism and ANFH.
Exacerbation of rheumatoid arthritis (RA). Preparations of iron, gold, thyrostatics can provoke the transition of RA into a severe form with systemic manifestations.
Hemarthrosis. Hemorrhage into the joint cavity occurs when using drugs that reduce blood clotting – warfarin, heparin, new oral anticoagulants. Hemorrhage in the knee and shoulder joints is characteristic.
Shoulder-hand syndrome (algodystrophic syndrome of the upper limb). Develops when taking anti-tuberculosis drugs.
Analgesic arthropathy. Occurs with prolonged use of NSAIDs, which inhibit anabolic processes in cartilage tissue.
Quinolone arthropathy. Develops with the use of antibiotics from the group of fluoroquinolones.
Complications with intra-articular administration of drugs. This form is extremely rare. The reason is insufficient antiseptic treatment of the injection site.
The main clinical manifestations are joint pain, hyperthermia and redness of the skin over the joints, difficulty in movement. These signs may appear immediately after taking the medication or after a certain time (from several days to several months). The nature of the course, the reversibility of changes, the defeat of certain groups of joints, the presence of effusion depends on the type of medicinal arthropathy.
Allergic arthritis is characterized by an acute course, volatile pains of moderate intensity, increasing with movement, damage to both large and small joints, their swelling, complete reversibility of changes. There are also other allergy symptoms (skin rashes, itching, rhinoconjunctivitis, bronchial asthma, Quincke’s edema). 2-4 joints are involved (oligoarthritis). There is a clear link between taking medication and the occurrence of arthritis.
For the development of microcrystalline arthritis, a long (months, years) intake of provoking drugs is necessary. For medicinal gout, acute severe pain is typical in one joint (most often in the I metatarsophalangeal) with pronounced swelling, redness of the skin. The slightest movement causes pain. The attack is accompanied by fever, chills, deterioration of general well-being. Gouty nodes (tofuses) are located on the skin of the auricles, the back surface of the elbow joints and hands. Pyrophosphate and hydroxyapatite arthropathies differ from gout in the absence of fever and tofuses, less severity and favorite localization (for pyrophosphate arthropathy – knee and wrist joints, for hydroxyapatite – shoulder). Microcrystalline arthritis leads to joint deformity.
Joint damage with medicinal lupus develops gradually – minor arthralgias of small joints appear, without signs of arthritis, having a migratory character. Along with arthropathy, fever, rash on the face in the form of a “butterfly”, erosion and ulcers in the mouth, anemic syndrome, nephrotic syndrome, pleurisy, pericarditis, neuropathies, psychoses are observed.
For ANFH, slowly increasing aching pains in the hip joint, giving to the groin, lower back or hip, restriction of rotation, flexion and extension are typical. With a prolonged course, the patient begins to limp when walking, the thigh muscles atrophy, the limb shortens. With the shoulder-hand syndrome, due to the defeat of the autonomic nerves, trophic disorders occur in the upper limb – at first persistent burning pains and swelling of the shoulder joint, then atrophy of the muscles of the shoulder girdle and hand, the development of tendon contractures and joint deformation.
Quinolone arthropathy is manifested by a symmetrical lesion of large joints with an acute onset (pain, swelling, restriction of movement), a transient nature, frequent inflammation of the tendons (mainly Achilles). With insufficient antiseptic treatment of the injection site during the injection of the drug into the joint, a picture of purulent arthritis sometimes unfolds. Fever, chills, sharp soreness and swelling of the joint appear. The skin above the joint turns red, becomes hot to the touch. Hemorrhage in the joint when using anticoagulants is accompanied by bursting pain in the joint, swelling, pronounced restriction of movement.
In the vast majority of cases, pathological changes in drug arthropathies are completely reversible. Any residual phenomena and serious complications occur extremely rarely. In the outcome of some forms, persistent pronounced deformities and contractures of the joints may develop, disabling patients. Inflammation of the Achilles tendon in case of non-compliance with rest may result in its rupture. Extensive ANFH requires surgical intervention on the hip joint. Purulent arthritis with untimely diagnosis and treatment can lead to phlegmon and sepsis.
In case of medicinal arthropathy, it is necessary to seek medical help from a rheumatologist or orthopedist. The diagnosis is made on the basis of the clinical picture and anamnesis data (mention of taking the drug). However, for the diagnosis of some forms of arthropathies of medicinal genesis, as well as for determining the degree of joint damage, additional research methods are needed:
- Laboratory. With medicinal gout, an increase in uric acid is noted in the biochemical analysis of blood. With hemarthrosis, signs of hypocoagulation are found in the coagulogram. With drug lupus syndrome, a decrease in leukocytes and erythrocytes, the presence of antinuclear antibodies and antibodies to single-chiral DNA are detected in the blood. The latter analysis is specific to medicinal lupus.
- Examination of synovial fluid. Puncture of the affected joint and microscopy of synovial fluid are performed. In microcrystalline arthritis, crystals of sodium monaurate or calcium pyrophosphate are visible on polarization microscopy. With purulent arthritis, the punctate has a cloudy color, contains a large number of neutrophils. If necessary, bacterial culture of the liquid is carried out with the determination of sensitivity to antibiotics.
- Instrumental. Imaging studies (ultrasound, radiography, MRI of joints) can determine changes in the structure of the subchondral bone (erosion, necrosis, sequestration), narrowing of the articular gap, calcification of cartilage and tendons, effusion into the articular cavity, swelling of the synovial membrane and periarticular tissues.
Medicinal arthropathies should be differentiated with joint diseases (osteoarthritis, osteochondrosis, trauma, rheumatoid arthritis, acute rheumatic fever, systemic lupus erythematosus). Allergic arthritis must be distinguished from systemic vasculitis occurring with an allergic component (Churge-Strauss syndrome, Schönlein-Genoch hemorrhagic vasculitis). Therapists, traumatologists, and allergists take part in the differential diagnosis.
The main treatment is to cancel the drug that caused the pathology of the joints, and to find an alternative medicine that is safer for the patient. Stopping taking drugs leads to a complete regression of symptoms. Sometimes no additional therapy is required. With severe pain syndrome, non-narcotic analgesics (diclofenac, ketorolac) are prescribed. Glucocorticosteroids (prednisone) are used to relieve severe inflammation of the joints, except in cases when GCS caused drug arthropathy. In allergic arthritis, GCS and antihistamines are effective. The development of purulent arthritis requires the use of antibiotics, taking into account sensitivity. While maintaining a high level of uric acid for a long time, hypouricemic drugs (allopurinol) are necessary.
Hemorrhage in the joint is an indication for a therapeutic puncture. In ANFH, conservative therapy includes drugs that improve microcirculation (dipyridamole, nicotinic acid), biphosphonates, vitamin D, chondroprotectors, physical therapy courses. In case of inefficiency, surgical treatment is performed (osteoplasty, transversal osteotomy).
Prognosis and prevention
In most cases, medicinal arthropathies have a favorable prognosis. After the withdrawal of the drug, there is a rapid regression of symptoms and restoration of the functional activity of the joints. Severe consequences have only some forms – ANFH, purulent arthritis, microcrystalline arthritis. Prevention of the development of pharmacologically induced arthropathy consists in avoiding the unjustified use of medications. Before prescribing a drug, it is necessary to find out whether the patient has chronic inflammatory diseases, allergic reactions to animal hair, plant pollen or other drugs.