Reactive arthritis in adults

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

ICD-10 code

M02 Reactive arthropathy.

Epidemiology

Epidemiological studies of reactive arthritis are limited, due to the lack of unified diagnostic criteria, the difficulty of testing this group of patients and the possibility of subclinical flow of 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 noted in the third decade of life. The ratio of men to women is from 25: 1 to 6: 1. The urinary form is much more common in men, but post-enterocolitis is equally common in men and women.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10]

What causes reactive arthritis?

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

The etiological factor of the genitourinary variant of the disease is Chlamydia trachomatis. 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 about 30% of sexually active people. The incidence of chlamydia is three times higher than the incidence of gonorrhea. There is a clear correlation of the level of infection with this microorganism with such signs as age younger than 25 years, risky sexual behavior with the change of partners, use of oral contraceptives.

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

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

How does reactive arthritis develop?

Reactive arthritis is accompanied by migration of the etiological 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. In the synovial membrane and CSF, live microorganisms capable of division are detected. Persistence of trigger microorganisms and their antigens in the tissues of the joint leads to the development of a chronic inflammatory process. The involvement of the infection in the development of the disease finds its confirmation in the detection of antibodies to chlamydial and intestinal infections, the association of the development or exacerbation of the joint syndrome with infectious diseases of the intestinal and genito-urinary tracts, as well as the positive, though not always distinct, effect of antibiotics in the treatment of reactive arthritis.

One of the main predisposing factors for the development of reactive arthritis is the carriage of HLA-B27, which is detected in 50-80% of patients. Its presence increases the probability of a urogenic variant of the disease 50-fold. It is believed that the protein produced by this gene participates in cellular immune responses, is a receptor for bacteria and thereby 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 their own tissues. Of the other predisposing factories, the inadequate, genetically conditioned response of CD4 T cells to infection, the characteristics of cytokine production, the inadequate elimination of microbes and their antigens from the joint cavity (ineffective immune repetition), the previous exposure of microbial antigens and microtraction of the joints are important.

Reactive Arthritis: Symptoms

Common symptoms of reactive arthritis include acute onset, a limited number of inflamed joints, predominantly of the lower extremities, asymmetry of the joints and axial skeleton, involvement of the tendon-ligament structures, the presence of extra-articular manifestations (aphthous stomatitis, keratoderma, zircinar balanitis, erythema nodosum, inflammatory eye disease); seronegativnchnost in the RF, a relatively benign course with a complete reverse development of inflammation, the possibility of recurrence of the disease, and in some cases, and xp tions inflammation localized in the peripheral joints and spine.

Reactive arthritis symptoms manifest after intestinal or genitourinary infection, while the period from it began before the appearance of the first symptoms is from 3 days to 1.5-2 months. Approximately 25% of men and women do not focus on the early symptoms of this disease.

Duration of joint damage is characterized by acute course and a limited number of affected joints. In 85% of patients mono- and oligoarthritis is observed. Typical is the asymmetric nature of joint damage. 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 pseudo-phalanx joints develops. Later, the joints of the upper limbs and spine can develop. The preferred localization of the pathological process is the metatarsophalangeal joints of the thumbs of the feet, which is observed in half of the cases. Less common are lesions of other metatarsophalangeal joints and interphalangeal joints of the toes, tarsus joints, ankle and knee joints. This disease often develops dactylites of one or several toes, most often the first, with the formation of sausage-shaped deformations, which are the result of inflammatory changes in periarticular structures and periosteal bone.

The interest of the tarsus joints and the inflammatory process in the ligamentous apparatus of the feet quickly lead to the development of pronounced flat feet ("gonorrheic foot"). The localization of the inflammatory process in the joints of the upper extremities with the interest of interphalangeal, metacarpophalangeal and radiocarpal joints is much less frequent. However, the stable process of this localization and, the more so, destruction of articular surfaces is not observed.

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

As the most characteristic of its variants, plantar aponeurosis (pain in the area of attachment of plantar aponeurosis to the lower surface of the calcaneus), achillobursitis, sausage-like defoguration of the toes, trochanteritis (pain in the region of large trochanteres of the femur with hip extraction) are considered as its most characteristic variants. Enterospaty gives the clinic a symphysitis, trochanteritis, a syndrome of anterior thorax because of the interest of the sterno-rib joints.

The presented clinical picture of joint damage is typical for acute course of reactive arthritis, it is observed in the first 6 months of the disease. Features of the chronic course of the disease, which lasts more than 12 months, consider the primary localization of lesions in the joints of the lower extremities and the tendency and decrease in their numbers, the increase in the expression of sacroiliitis, persistent and resistant to the treatment of enteropathy.

In the debut of the disease, the symptoms of reactive arthritis and axial skeletal lesions, found in 50% of patients, manifest pain in the projection of the sacroiliac joint and / or the lower part of the spine, limiting its mobility. Pain in the spine is accompanied by morning stiffness and spasm of paravertebral muscles. However, x-ray changes in the axial skeleton are not typical, they are met only in 20% of cases.

One- and two-sided sakroileitis is found in 35-45% of patients, the frequency of its detection directly correlates with the duration of the disease. Although bilateral lesions of the sacroiliac joints are characteristic, they are often observed unilateral, especially in the early stages of the disease. In 10-15% of cases wind spondilitis, which is characterized by radiographic signs in the form of a "jumping" type of location of asymmetric syndesmophytes and paraspinal ossifits.

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

Observe other systemic symptoms of reactive arthritis. Fever is one of the characteristic manifestations of this disease. Sometimes it has a hectic character, resembling a septic process. There may be anorexia, a decrease in the weight of the village, increased fatigue. Defeat of the heart is met in approximately 6-10% of patients, it occurs with a mild clinical symptomatology, and it is detected, as a rule, using instrumental survey methods. On ECG are found the violation of atrioventricular conduction up to the development of complete atrioventricular blockade of ST segment deviation. Possible development of aortitis, carditis, valvulitis with the formation of aortic insufficiency. Rarely are there apical fibrosis of the lungs, adhesive pleurisy, glomerulonephritis with proteinuria and microhematuria, amyloidosis of the kidneys, thrombophlebitis of the lower extremities, peripheral neuritis, and these changes are more often detected in patients with chronic course.

Eye defeat 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 includes along with urethritis and articular syndrome in the classic triad of this disease. Conjunctivitis is one-and two-sided and can be accompanied by pain and burning in the eyes, an injection of vessels of the sclera. Conjunctivitis, like urethritis, can occur with an erased clinical picture and last no more than 1-2 days.

But often it is protracted and lasts from several days to several weeks. Acute anterior uveitis - a typical manifestation of spondyloarthropathies - is also met with reactive arthritis, and more often than with Bechterew's disease. As a rule, acute anterior uveitis is one-sided, it is associated with carrier HLA-B27 and is considered a reflection of a recurrent or chronic course of the disease, leading to a significant reduction in visual acuity. Perhaps the development of keratitis, ulcers of the cornea and posterior uveitis.

Classification

There are two main firms of reactive arthritis: urogenital and post-enterocolitic. For the urogenital form of the disease sporadic cases of the disease are characteristic. In contrast, postterecolithic reactive arthritis is detected at the same time by several people in closed groups, youth camps; it is associated with poor sanitation. There are no significant differences in the clinical manifestations of these forms.

[11], [12], [13], [14], [15], [16], [17]

How to recognize reactive arthritis?

To diagnose the disease, the classification criteria adopted at the IV International Workshop on the Diagnosis of Reactive Arthritis are used. There are two large criteria.

1. asymmetry of the joint, involvement of 1-4 joints and localization of the pathological process in the joints on the lower limbs (two of three such signs are necessary);
2. clinically manifested infection of the intestinal and genitourinary tract (enteritis or urethritis 1-3 days - 6 weeks before the disease develops).

Small criteria include:

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

"Specific" reactive arthritis is diagnosed if there are two large criteria and the corresponding small ones, and "possible" reactive arthritis - if there are two large criteria without corresponding small or one large and one of the small criteria.

Laboratory diagnostics of reactive arthritis

To detect chlamydial infection, a direct immunofluorescence reaction is used, which is considered as 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. In addition, a polymerase chain reaction is used, a serological study with species-specific antisera of three classes of immunoglobulins, as well as a culture method that is considered most specific. If the result of the culture method is positive, other studies that indicate the infection of the organism are not used. In the absence of a culture method, it is necessary to obtain a positive result in any two reactions.

Other laboratory studies have little diagnostic significance, although they characterize the activity of the inflammatory process. CRP is more adequate than ESR, it reflects the activity of the inflammatory process. There may be leukocytosis and thrombocytosis, moderate anemia. Diagnosis and prognostic value has the carriage of HLA-B27. This gene predisposes not only to localization of the inflammatory process in the axial skeleton, but also is associated with many systemic manifestations of reactive arthritis. The HLA-B27 trial is useful in diagnosing the early stage of the disease and in individuals with incomplete Reiter syndrome.

Example of the formulation of the diagnosis

When formulating the diagnosis of reactive arthritis in each specific case, it is necessary to isolate the form (urogenital, post-enterocolitis), the nature of the process (primary, recurrent); variant of the current (acute, prolonged, chronic); clinical and morphological characteristics of the lesion of the urogenital organs (urethritis, epididymitis, prostatitis, balanoposthitis, cervicitis, endometritis, salpingitis), organ of vision (conjunctivitis, acute anterior uveitis), musculoskeletal system (mono-, oligo-, polyarthritis, sakroileitis, spondylitis, enthesopathy); radiologic characteristics (according to Steinbroke), sacroiliitis (according to Kellgren or Dale), spondylitis (syndesmophytes, paraspinal ossitis, ankylosis of the intervertebral joints), degree of activity and functional capacity of the locomotor apparatus.

[18], [19], [20], [21], [22], [23], [24], [25]

Treatment of reactive arthritis

Treatment of reactive arthritis involves the sanation of a foci of infection in the genitourinary tract or intestine, the suppression of the inflammatory process in the joints and other organs, and rehabilitation. Rational antibiotic therapy includes the use of optimal doses of drugs and their long (about 4 weeks) use, which is explained by intracellular persistence of trigger microorganisms and the presence of their resistant strains. Timely prescribed antibiotics in the urogenital form of the disease shorten the duration of the joint attack and can prevent relapse of the disease in the case of exacerbation of urethritis to a lesser extent antibiotics affect the course of chronic urogenital inflammation of the joints. It should be borne in mind that the treatment of non-gonococcal urethritis in patients with reactive arthritis also prevents recurrence of arthritis. In the postterocolitic variant, antibiotics do not affect the duration and prognosis of the disease as a whole, which is probably due to 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.

Chlamydial reactive arthritis treatment involves the administration 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, roxitromicin 0, 1 g, clarithromycin 0.5 g,
• Tetracyclines: doxycycline 0.3 g.
• Fgorhinolony: ciprofloxation 1.5 g, ofloxacin 0.6 g, lomefloxacin 0.8 g, pefloxacin 0.8 g.

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

To suppress the inflammatory process in the joints, entheses and spine appoint NSAIDs, which are considered drugs of the first line of therapy. When the disease persists and the ineffectiveness of NSAIDs, glucocorticosteroids are prescribed (prednisolone per os not more than 10 mg / day). A more pronounced therapeutic effect is observed in intraarticular and periarticular administration of HA. Possible introduction of HA in the sacroiliac joints under the control of CT. With prolonged and chronic course of the disease, it is advisable to prescribe the HDL and, above all, sulfasalazine 2.0 g / day, which gives a positive result in 62% of cases with a half-year duration of such treatment. If sulphasalazine is ineffective, methotrexate is advisable, with therapy starting at 7.5 mg / week and gradually increasing the dose to 15-20 mg / week.

Recently, with resistant to therapy variants of reactive arthritis, use mantles of TNF-α infliximab. Biological agents contribute to the resolution not only of reactive arthritis of peripheral joints and spondylitis, but also enthesitis, dactylitis and acute anterior uveitis.

What prognosis does reactive arthritis have?

Reactive arthritis with read auspicious in the vast majority of patients. In 35% of cases, its duration does not exceed 6 months, relapse of the disease is not observed later. Another 35% of patients have a recurring course, and relapse of the disease can be manifested only by articular syndrome, enthesitis, or, rarely, by systemic manifestations. Approximately 25% of patients with reactive arthritis have a primarily chronic course of the disease with slow progression.

In other cases, the severe course of the disease has been observed for many years with the development of a destructive process in the joints or ankylosing spondylitis, which is difficult to distinguish from an idiopathic AS. Risk factors for adverse prognosis and possible chronic disease include low effectiveness of NSAIDs, inflammation of the hip joints, limitation of spinal mobility, intestinal deficit of the toes, oligoarthritis, onset of the disease to 16 years of age, high laboratory activity for three months or more, and male sex, presence of extra-articular manifestations, carriage of HLA-B27, urogenous form of the disease. Individual characteristics of trigger microorganisms, apparently, play a determining role in the course of the disease. The most rarely recurrent course is observed in such diseases as iersiniosis (up to 5%), more often (up to 25%) salmonella and even more often (up to 68%) reactive arthritis, induced by Chlamydia infection.