Reactive arthritis in adults

Reactive arthritis of the joints is a non-purulent "sterile" inflammatory disease of the musculoskeletal system, induced by infections of extra-articular localization, primarily of the genitourinary or intestinal tract. Along with ankylosing spondylitis and psoriatic joint damage, reactive arthritis is included in the group of seronegative spondyloarthritis, which is associated with damage to the sacroiliac joints and spine.

ICD-10 code

M02 Reactive arthropathies.

Epidemiology

Epidemiological studies of reactive arthritis are limited due to the lack of unified diagnostic criteria, difficulty in examining this group of patients, and the possibility of subclinical infections associated with reactive arthritis. The incidence of reactive arthritis is 4.6-5.0 per 100,000 population. The peak of their development is observed in the third decade of life. The ratio of men to women is from 25:1 to 6:1. The genitourinary form is much more common in men, but the postenterocolitic form is equally common in men and women.

[ 1 ], [ 2 ], [ 3 ], [ 4 ], [ 5 ]

What causes reactive arthritis?

Etiological agents are considered to be Chlamydia trachomatis, Yersinia enterocolitica, Salmonella enteritidis, Campylobacter jejuni, Shigella flexneri. Arthritis-causing properties of some strains of Chlamydia pneumoniae and Chlamydia psittaci are discussed. The etiological role of Clostridium difficile, Ureaplasma urealyticum, Mycoplasma hominis, Neisseria gonorrhoeae in the development of reactive arthritis has not been proven.

Chlamydia trachomatis is considered to be the etiologic factor of the urogenital variant of the disease. This microorganism is identified in 35-69% of patients with reactive arthritis. Chlamydial infection is one of the most common. In Europe, it is found in approximately 30% of sexually active people. The incidence of chlamydia is three times higher than the incidence of gonorrhea. A clear correlation has been noted between the level of infection with this microorganism and such signs as age under 25, risky sexual behavior with a change of partners, and the use of oral contraceptives.

Chlamydia is an etiologic factor not only of reactive arthritis, but also of trachoma, venereal lymphogranuloma, ornithosis, and interstitial pneumonia. Chlamydia trachomatis, which contributes to the development of the urogenital variant of the disease, has five serotypes (D, E, F, G, H, I, K), and is considered an obligate intracellular microorganism transmitted sexually. Chlamydial infection often occurs with an erased clinical picture, is found 2-6 times more often than gonorrhea, and is often activated under the influence of another urogenital or intestinal infection.

In men, it manifests itself as rapidly transient anterior or total urethritis with scanty mucous discharge from the urethra, itching, and dysuria. Less common are epididymitis and orchitis, and prostatitis is extremely rare. In women, cervicitis, vaginitis, endometritis, salpingitis, and salpingo-oophoritis are observed. Chlamydial infection in women is characterized by discomfort in the external genitalia, pain in the lower abdomen, mucopurulent discharge from the cervical canal, and increased contact bleeding of the mucous membrane. Complications of chronic chlamydial infection in women include infertility or ectopic pregnancy. A newborn born to a mother infected with chlamydia may develop chlamydial conjunctivitis, pharyngitis, pneumonia, or sepsis. In addition, the above serotypes of Chlamydia trachomatis can cause follicular conjunctivitis, anorectal lesions, and perihepatitis. Urogenital symptoms are equally common in urogenital and postenterocolitic variants of the disease and do not depend on the characteristics of the trigger factor.

How does reactive arthritis develop?

Reactive arthritis is accompanied by the migration of the etiologic agent from the foci of primary infection to the joints or other organs and tissues of the body by phagocytosis of microorganisms by macrophages and dendritic cells. Live microorganisms capable of division are found in the synovial membrane and cerebrospinal fluid. Persistence of trigger microorganisms and their antigens in the joint tissues leads to the development of a chronic inflammatory process. The participation of infection in the development of the disease is confirmed by the detection of antibodies to chlamydial and intestinal infections, the association of the development or exacerbation of joint syndrome with infectious diseases of the intestinal and genitourinary tracts, as well as the positive, although not always clear, effect of antibiotics in the treatment of reactive arthritis.

One of the main predisposing factors for the development of reactive arthritis is considered to be the carriage of HLA-B27, which is detected in 50-80% of patients. Its presence increases the probability of the urogenic variant of the disease by 50 times. It is believed that the protein produced by this gene is involved in cellular immune reactions, is a receptor for bacteria and thus contributes to the persistence of infection in the body, and also has common antigenic determinants with microbial peptides and body tissues, and as a result, the immune response is directed not only against the infectious agent, but also against the body's own tissues. Other predisposing factors include an inadequate, genetically determined response of CD4 T cells to infection, features of cytokine production, insufficient elimination of microbes and their antigens from the joint cavity (ineffective immune response), previous exposure to microbial antigens and microtraumatization of joints.

Reactive arthritis: symptoms

Common symptoms of reactive arthritis include acute onset, a limited number of inflamed joints, mainly in the lower extremities, asymmetry of joint and axial skeletal lesions, involvement of tendon-ligament structures, presence of extra-articular manifestations (aphthous stomatitis, keratoderma, circinate balanitis, erythema nodosum, inflammatory eye lesions), seronegativity according to the Russian Federation, a relatively benign course with complete regression of inflammation, the possibility of relapses of the disease, and in some cases, chronicity of the inflammatory process with localization in the peripheral joints and spine.

Reactive arthritis symptoms appear after an intestinal or genitourinary infection, and the period from its onset to the appearance of the first symptoms is from 3 days to 1.5-2 months. About 25% of men and women do not focus on the early symptoms of this disease.

Joint lesions are characterized by an acute course and a limited number of affected joints. Mono- and oligoarthritis are observed in 85% of patients. Asymmetrical nature of joint lesions is considered typical. In all cases, lesions of the joints of the lower extremities are observed, with the exception of the hip joints. At the very beginning of the disease, inflammation of the knee, ankle and metatarsophalangeal joints develops. Later, lesions of the joints of the upper extremities and spine may develop. The favorite localization of the pathological process is the metatarsophalangeal joints of the big toes, which are observed in half of the cases. Less often, lesions of other metatarsophalangeal joints and interphalangeal joints of the toes, tarsal joints, ankle and knee joints are detected. With this disease, dactylitis of one or more toes often develops, most often the first, with the formation of a sausage-shaped deformation, which is the result of inflammatory changes in the periarticular structures and periosteal bone.

The involvement of the tarsal joints and the inflammatory process in the ligamentous apparatus of the feet quickly lead to the development of pronounced flatfoot ("gonorrhoeal foot"). Much less often, the localization of the inflammatory process in the joints of the upper extremities with the involvement of the interphalangeal, metacarpophalangeal and wrist joints is observed. However, a persistent process of this localization and especially destruction of the articular surfaces is not observed.

One of the characteristic symptoms of reactive arthritis is enthesopathies, observed in every fourth or fifth patient. This symptom is typical for the entire group of spondyloarthritis, but is most clearly represented in this disease. Clinical enthesopathy is accompanied by pain during active movements in the area of the affected entheses with or without local swelling.

The most typical variants include plantar aponeurosis (pain in the area of attachment of the plantar aponeurosis to the lower surface of the calcaneus), Achilles bursitis, sausage-shaped defiguration of the toes, trochanteritis (pain in the area of the greater trochanters of the femur when abducting the hip). Enthesopathy gives the clinical picture of symphysitis, trochanteritis, anterior chest syndrome due to involvement of the sternocostal joints.

The presented clinical picture of joint damage is characteristic of the acute course of reactive arthritis, it is observed in the first 6 months of the disease. The features of the chronic course of the disease, which lasts more than 12 months, are considered to be the predominant localization of damage in the joints of the lower extremities and the tendency to decrease their number, increasing severity of sacroiliitis, persistent and resistant to treatment enthesopathies.

At the onset of the disease, symptoms of reactive arthritis and axial skeletal damage, detected in 50% of patients, are manifested by pain in the projection area of the sacroiliac joints and/or the lower part of the spine, limitation of its mobility. Pain in the spine accompanies morning stiffness and spasm of the paravertebral muscles. However, radiographic changes in the axial skeleton are atypical, they are found only in 20% of cases.

Unilateral and bilateral sacroiliitis is found in 35-45% of patients, the frequency of its detection directly correlates with the duration of the disease. Although bilateral damage to the sacroiliac joints is typical, unilateral damage is also often observed, especially in the early stages of the disease. In 10-15% of cases, spondylitis is observed, which is characterized by radiological signs in the form of a "jumping" type of location of asymmetric syndesmophytes and paraspinal ossifications.

Blenorrhagic keratoderma is the most characteristic skin symptom of reactive arthritis; it is characterized by painless papulosquamous rashes, most often on the palms and soles, although they can be localized on the trunk, proximal parts of the extremities, and the scalp. Histologically, this type of skin lesion is indistinguishable from pustular psoriasis. Onychodystrophy is characteristic of the chronic course and includes subungual hyperkeratosis, discoloration of the nail plates, onycholysis, and onychogryphosis.

Other systemic symptoms of reactive arthritis are also observed. Fever is one of the characteristic manifestations of this disease. Sometimes it is hectic in nature, resembling a septic process. There may be anorexia, weight loss, increased fatigue. Heart damage occurs in approximately 6-10% of patients, it occurs with scanty clinical symptoms, and is usually detected using instrumental examination methods. The ECG reveals a violation of atrioventricular conduction up to the development of complete atrioventricular block of ST segment deviation. Aortitis, carditis, valvulitis with the formation of aortic insufficiency are possible. Rarely encountered are apical pulmonary fibrosis, adhesive pleurisy, glomerulonephritis with proteinuria and microhematuria, renal amyloidosis, thrombophlebitis of the lower extremities, peripheral neuritis, and these changes are more often detected in patients with a chronic course.

Eye damage is found in most patients. Conjunctivitis is detected in 70-75% of patients. It is considered one of the earliest signs of reactive arthritis and is included in the classic triad of this disease along with urethritis and articular syndrome. Conjunctivitis can be unilateral or bilateral and may be accompanied by pain and burning in the eyes, injection of scleral vessels. Conjunctivitis, like urethritis, can proceed with an erased clinical picture and last no more than 1-2 days.

But it is often protracted and lasts from several days to several weeks. Acute anterior uveitis is a typical manifestation of spondyloarthropathies and is also encountered in reactive arthritis, and more often than in Bechterew's disease. As a rule, acute anterior uveitis is unilateral, it is associated with the carriage of HLA-B27 and is considered a reflection of the recurrent or chronic course of the disease, leading to a significant decrease in visual acuity. Keratitis, corneal ulcers and posterior uveitis may develop.

Classification

There are two main types of reactive arthritis: urogenital and post-enterocolitic. The urogenital form of the disease is characterized by sporadic cases of the disease. On the contrary, post-enterocolitic reactive arthritis is detected simultaneously in several people in closed groups, youth camps; it is associated with unfavorable sanitary conditions. There are no significant differences in the clinical manifestations of these forms.

[ 6 ], [ 7 ], [ 8 ], [ 9 ], [ 10 ]

How to recognize reactive arthritis?

To diagnose the disease, classification criteria adopted at the IV International Working Conference on the Diagnosis of Reactive Arthritis are used. Two major criteria are distinguished.

1. asymmetry of joint damage, involvement of 1-4 joints and localization of the pathological process in the joints of the lower extremities (the presence of two of these three signs is required);
2. clinically manifest infection of the intestinal and genitourinary tracts (enteritis or urethritis 1-3 days - 6 weeks before the development of the disease).

Minor criteria include:

1. laboratory confirmation of genitourinary or intestinal infection (detection of Chlamydia trachomatis in scrapings from the urethra and cervical canal or detection of enterobacteria in feces);
2. detection of an infectious agent in the synovial membrane or cerebrospinal fluid using polymerase chain reaction.

“Definite” reactive arthritis is diagnosed in the presence of two major criteria and corresponding minor criteria, and “possible” reactive arthritis is diagnosed in the presence of two major criteria without corresponding minor criteria or one major and one of the minor criteria.

Laboratory diagnostics of reactive arthritis

To detect chlamydial infection, a direct immunofluorescence reaction is used, which is considered a screening method. The sensitivity of this method is 50-90% depending on the experience of the doctor and the number of elementary bodies in the sample being tested. In addition, a polymerase chain reaction, a serological study with species-specific antisera of three classes of immunoglobulins, and a culture method, which is considered the most specific, are used. If the culture method is positive, other studies indicating infection of the organism are not used. In the absence of a culture method, a positive result must be obtained in any two reactions.

Other laboratory tests have little diagnostic value, although they characterize the activity of the inflammatory process. CRP reflects the activity of the inflammatory process more adequately than ESR. Leukocytosis and thrombocytosis, moderate anemia are possible. The carriage of HLA-B27 has diagnostic and prognostic value. This gene predisposes not only to localization of the inflammatory process in the axial skeleton, but is also associated with many systemic manifestations of reactive arthritis. The study of HLA-B27 is advisable in the diagnosis of the early stage of the disease and in individuals with incomplete Reiter's syndrome.

Example of diagnosis formulation

When formulating a diagnosis of reactive arthritis in each specific case, it is necessary to highlight the form (urogenital, postenterocolitic), the nature of the process (primary, recurrent); the course variant (acute, protracted, chronic); clinical and morphological characteristics of the lesion of the genitourinary organs (urethritis, epididymitis, prostatitis, balanoposthitis, cervicitis, endometritis, salpingitis), the organ of vision (conjunctivitis, acute anterior uveitis), the musculoskeletal system (mono-, oligo-, polyarthritis, sacroiliitis, spondylitis, enthesopathies); radiological characteristics (according to Steinbrocker), sacroiliitis (according to Kellgren or Dale), spondylitis (syndesmophytes, paraspinal ossifications, ankylosis of the intervertebral joints), the degree of activity and the functional capacity of the locomotor apparatus.

[ 11 ], [ 12 ], [ 13 ], [ 14 ], [ 15 ], [ 16 ]

Treatment of reactive arthritis

Treatment of reactive arthritis involves sanitizing the source of infection in the genitourinary tract or intestines, suppressing the inflammatory process in the joints and other organs, and rehabilitation measures. Rational antibacterial therapy includes the use of optimal doses of drugs and their long-term (about 4 weeks) use, which is explained by the intracellular persistence of trigger microorganisms and the presence of their resistant strains. Timely prescribed antibiotics for the urogenic form of the disease shorten the duration of a joint attack and can prevent a relapse of the disease in the event of an exacerbation of urethritis; antibiotics have a lesser effect on the course of chronic urogenic joint inflammation. It should be borne in mind that the treatment of non-gonococcal urethritis in patients with reactive arthritis also prevents relapses of arthritis. In the postenterocolitic variant, antibiotics do not affect the duration and prognosis of the disease as a whole, which is probably due to the rapid elimination of the pathogen. The positive effect of some antibiotics, in particular doxycycline, is associated with the effect on the expression of matrix metalloproteinases and with collagenolytic properties.

Treatment of chlamydial reactive arthritis involves the use of macrolides, tetracyclines and, to a lesser extent, fluoroquinolones, which have relatively low activity against Chlamidia trachomatis.

Optimal daily doses

• Macrolides: azithromycin 0.5-1.0 g, roxithromycin 0.1 g, clarithromycin 0.5 g,
• Tetracyclines: doxycycline 0.3 g.
• Phorquinolones: ciprofloxacin 1.5 g, ofloxacin 0.6 g, lomefloxacin 0.8 g, pefloxacin 0.8 g.

Sexual partners of a patient with urogenital (chlamydial) reactive arthritis should also undergo a two-week course of antibacterial therapy, even if they have negative results of examination for chlamydia. Treatment of reactive arthritis should be carried out under microbiological control. If the first course of therapy is ineffective, a second course should be carried out with an antibacterial drug of another group.

To suppress the inflammatory process in the joints, entheses and spine, NSAIDs are prescribed, which are considered first-line drugs. In case of persistent course of the disease and ineffectiveness of NSAIDs, resort to the prescription of glucocorticosteroids (prednisolone per os no more than 10 mg / day). A more pronounced therapeutic effect is observed with intra-articular and periarticular administration of GC. It is possible to administer GC into the sacroiliac joints under CT control. In case of protracted and chronic course of the disease, it is advisable to prescribe DMARDs and, above all, sulfasalazine 2.0 g / day, which gives a positive result in 62% of cases with a six-month duration of such treatment. If sulfasalazine is ineffective, it is advisable to use methotrexate, while therapy is started with 7.5 mg / week and the dose is gradually increased to 15-20 mg / week.

Recently, in resistant to therapy variants of reactive arthritis, the TNF-a mantra infliximab has been used. Biological agents contribute to the resolution of not only reactive arthritis of the peripheral joints and spondylitis, but also enthesitis, dactylitis and acute anterior uveitis.

What is the prognosis for reactive arthritis?

Reactive arthritis is considered favorable in the vast majority of patients. In 35% of cases, its duration does not exceed 6 months, and relapses of the disease are not observed in the future. Another 35% of patients have a recurrent course, and a relapse of the disease can manifest itself only as articular syndrome, enthesitis, or, much less often, systemic manifestations. Approximately 25% of patients with reactive arthritis have a primarily chronic course of the disease with slow progression.

In other cases, severe course of the disease is observed over many years with development of destructive process in joints or ankylosing spondylitis, difficult to distinguish from idiopathic AS. Risk factors of unfavorable prognosis and possible chronicity of the disease are considered to be low efficiency of NSAIDs, inflammation of the hip joints, limited mobility of the spine, intestinal defiguration of the toes, oligoarthritis, onset of the disease before the age of 16, high laboratory activity for three months or more, as well as male gender, presence of extra-articular manifestations, carriage of HLA-B27, urogenic form of the disease. Individual characteristics of trigger microorganisms, apparently, play a decisive role in the course of the disease. The most rare recurrent course is observed in diseases such as yersiniosis (up to 5%), more often (up to 25%) salmonellosis, and even more often (up to 68%) reactive arthritis induced by chlamydial infection.