Oligoarthritis refers to the simultaneous inflammation of several, but not more than four joints. It is a general term that describes a condition to be encountered in patients suffering from distinct autoimmune, infectious or idiopathic diseases, e.g., oligoarticular juvenile idiopathic arthritis, reactive arthritis, and psoriatic arthritis.
Patients suffering from oligoarthritis typically present with symptoms associated with joint inflammation and functional impairment of joints. Affected joints are usually tender, and patients claim arthralgia. Closer inspection may reveal joint swelling or joint effusion, and chronic disease may result in joint deformities. Generally, motion ranges are reduced, and patients describe stiffness. Movements may induce crepitation.
Anamnestic data, symptom onset, distribution patterns as well as disease progression largely depend on the underlying disease. The following examples shall illustrate the diversity of clinical pictures presented by oligoarthritis patients as well as the importance of thorough anamnesis and physical examination.
- OJIA is diagnosed in patients presenting with juvenile idiopathic arthritis if no more than four joints are affected within the first six months after symptom onset. The number of affected joints may increase afterwards, and depending on disease progression, persistent and extended OJIA are distinguished. Knees, ankles and wrists are most commonly compromised. OJIA patients may additionally show symptoms of ocular inflammation, namely of uveitis or iritis. Of note, the latter may not provoke clinical symptoms and may remain undiagnosed unless an ophthalmologic examination is performed.
- Asymmetric oligoarthritis of the lower limbs is typical of RA, although sacroilitis may also be diagnosed. Conjunctivitis, keratitis, episcleritis, uveitis, rash and enthesitis as well as proteinuria and microhematuria are presented by some affected individuals . Diagnosis of RA is largely facilitated if patients report a recent genitourinary or gastrointestinal infection.
- PA may manifest in form of asymmetric oligoarthritis mainly affecting medium to large joints, or in form of symmetric joint inflammation with a predilection for metacarpophalangeal and proximal interphalangeal joints. Moreover, distal interphalangeal joints, spine and sacroiliac joints may be compromised . A medical or family history of psoriasis is of great diagnostic value, and patients may show cutaneous lesions characteristic of psoriasis as well as nail pits, dactylitis and bone lesions at enthesial sites.
Of note, joint inflammation may not induce clinical symptoms at all .
Entire Body System
A 50-year-old Vietnamese boat refugee presented with an oligoarthritis which had been present for the two years since her arrival in The Netherlands. [ncbi.nlm.nih.gov]
It is possible that several JIA susceptibility genes reside within the MHC, thus explaining the plethora of HLA associations with disease. However, the region is characterized by linkage disequilibrium (LD) extending over megabases of DNA (12). [onlinelibrary.wiley.com]
- Joint Swelling
Symptoms tend to be limited to joint swelling and pain. But it can also include uneven bone growth. This can lead to one leg being longer than the other. [pinnaclehealth.org]
- Back Pain
Ankylosing spondylitis (AS) is an inflammatory disease that is characterized by inflammatory back pain and asymmetric peripheral oligoarthritis [1-4]. * Oligoarthritis Caused by Borrelia bavariensis, Austria, 2014 Asymmetric oligoarthritis. [medical-dictionary.thefreedictionary.com]
Huerta-Sil, et al.  reported the findings in 50 patients with peripheral arthritis and inflammatory back pain with disease duration of 5.4 years after 3-5 years. [openaccessjournals.com]
Up until now, the patient had managed these episodes with rest, paracetamol and diclofenac (prescribed originally for mechanical back pain) as required. He had no family history of arthritis. He was a non-smoker and drank 4 units of alcohol weekly. [bjgp.org]
(%) 25 (49) Back pain, no. (%) 12 (24) Baseline HAQ score, median (95% CI) 5 (4, 6) Unable to work because of arthritis, no. [onlinelibrary.wiley.com]
Any other forms of joint or back pain during or after the acute infection were also recorded. [academic.oup.com]
Behçet's disease Arthralgia is seen in up to half of patients, and is usually a non-erosive poly or oligoarthritis primarily of the large joints of the lower extremities. [wordsimilarity.com]
Box 2: Musculoskeletal manifestations of coeliac disease Generalised arthralgia. Muscle weakness and fatigue. Metabolic bone disease: osteomalacia and/or osteoporosis. Clubbing. Muscle cramps and tetany. [pmj.bmj.com]
She presented with a 3-week history of fever, arthralgia, swollen neck and pustular lesions on her hands, accompanied by pain. [reumatologiaclinica.org]
Arthralgia Arthralgia is the most common but non-specific articular complaint of HIV-positive patients. It tends to occur in the acute phase of the infection and is the result of direct infection of the joint by the virus. [sajr.org.za]
Case Presentation In February 2008, a 12-year-old girl developed the flu with high fever, malaise, headaches, photophobia, myalgia and arthralgia. PCR and viral culture of a nasopharyngeal swab demonstrated influenza B virus. [ped-rheum.biomedcentral.com]
- Joint Effusion
Lyme arthritis must be considered in patients from Europe who have persisting joint effusions. [ncbi.nlm.nih.gov]
After the patient was treated with amoxicillin (500 mg 3 /d for 28 days) ( 4 ), all joint effusions resolved. At his 9-month follow-up visit, the patient did not report any symptoms. [wwwnc.cdc.gov]
Contrast-enhanced MRI showed joint effusion and thickening of the synovial membrane (Figure 4). [jmedicalcasereports.biomedcentral.com]
- Joint Deformity
Surgery Surgical treatment may be used in a very small number of children whose juvenile idiopathic arthritis (JIA) has caused severe joint deformity, loss of movement, or pain. [uwhealth.org]
Closer inspection may reveal joint swelling or joint effusion, and chronic disease may result in joint deformities. Generally, motion ranges are reduced, and patients describe stiffness. Movements may induce crepitation. [symptoma.com]
Oligoarthritis may be diagnosed in patients presenting with arthralgia and symptoms indicating an ongoing inflammation in up to four joints, but additional measures may be necessary to identify subclinical joint disease. Laboratory analyses of blood samples, sonography and possibly invasive techniques may be very helpful to that end. Oligoarthritis is typically associated with elevated concentrations of serum inflammatory markers like C-reactive protein, and the erythrocyte sedimentation rate is usually enhanced. Leukocytosis is characteristic of acute inflammatory disorders. Sonography has been successfully used to diagnose subclinical joint inflammation. Eventually, joint biopsies may be carried out to support a tentative diagnosis and to rule out more severe differential diagnoses. Malignancies don't usually provoke oligoarthritis, but neoplasms have occasionally been related with this disorder .
In order to identify the underlying disease, target-oriented measures should be chosen based on a list of likely differential diagnoses. In this regards, workup may comprise the following:
- Determination of titers of autoantibodies like rheumatoid factor and anti-cyclic citrullinated peptide antibodies since patients suffering from an autoimmune disease like OJIA or PA often test positive for such antibodies
- Human leukocyte antigen testing, because HLA-B27 genetically predisposes for PA, but is also related to enthesitis-related arthritis, a subtype of juvenile idiopathic arthritis
- Bacteriological culture of blood and synovial fluid samples, with positive results implying septic oligoarthritis
- Molecular biological assays to identify nucleic acids in synovial fluid specimens obtained from RA patients that usually yield negative results in bacteriological culture
- Diagnostic imaging to assess the extent of joint lesions and to reveal additional anomalies of bones and connective tissue
- Urine analysis since renal function impairment is occasionally seen in oligoarthritis patients
It is of utmost important to make a precise diagnosis and to chose an adequate therapeutic regimen to avoid further damage to cartilage, underlying bone and other anatomical structures compromised by joint inflammation. Although symptomatic therapy may help to relieve arthralgia and to restore motion ranges, cure of the primary disease is the best way to avoid recurrence. Although the latter may occur spontaneously - e.g., in case of RA - analgesic and anti-inflammatory medication may mask the underlying disease and cause detrimental diagnostic delays .
Symptomatic treatment generally consists in the administration of non-steroidal antiinflammatory drugs that reduce pain and inflammation. In case of persistent or exacerbating arthritis, corticosteroid therapy may be considered. Corticosteroids may be applied per os, parenterally or intraarticularly. Furthermore, disease-modifying antirheumatic drugs like azathioprine, methotrexate, etanercept and infliximab may be administered to control immune-mediated oligoarthritis. However, long-term administration of such drugs may be associated with safety risks, and evidence regarding their effectivity is often scarce. With regards to OJIA, only methotrexate has been shown to be superior to conventional treatment as described before . For treatment of PA, tumor necrosis factor-α inhibitors like etanercept; ustekinumab, a monoclonal antibody targeting interleukin-12 and -23; and secukinumab, an antibody directed against interleukin-17A, may be used . Antibiotics may be indicated in case of RA, although evidence of beneficial effects has only been provided for determined forms of the disease. In this context, antimicrobial treatment is generally recommended for post-streptococcal RA. If arthritis has already developed after genitourinary or gastrointestinal infections, antibiotics are of little use .
Surgical interventions are rarely required.
Patients diagnosed with oligoarthritis due to primary disorders potentially associated with ocular and renal damage should undergo regular ophthalmological examinations and urine analyses.
Entities causing oligoarthritis are associated with distinct prognoses:
- OJIA, for instance, may remit (23% within six years) or exacerbate to polyarticular juvenile idiopathic arthritis (50% within that same time frame), as has been shown in a French study . According to that same study, about a third of affected individuals develops joint erosions or uveitis at young ages. Here, high erythrocyte sedimentation rates have been proven to predict a destructive course of the disease. These observations do not support the commonly accepted hypothesis of OJIA being a benign form of juvenile idiopathic arthritis that is outgrown until adulthood. In fact, a metaanalysis has shown OJIA remission rates to range from 36 to 84% , and these data imply an uncertain prognosis until further favorable and unfavorable prognostic factors can be identified.
- Spontaneous remission within six months is observed in about 50% of RA patients, but patients may also become asymptomatic at later points in time. About 20% of affected individuals develop chronic arthritis .
- PA generally follows a course of apparent remission and recurrence. While adequate treatment may momentarily relieve symptoms, permanent cure is unlikely. In fact, more than half of PA patients develop disabling polyarthritis and present with five or more deformed joints within one or two decades after symptom onset . In this context, oligoarticular onset and lower erythrocyte sedimentation rates have been identified as favorable prognostic factors, whereas polyarthritis and the need for high-dose drug therapy after initial diagnosis predict more rapid progression.
Oligoarthritis may be developed by patients suffering from a wide variety of diseases. Few entities are primarily related to an inflammation of more than one but less than five joints. OJIA, RA and PA as well as undifferentiated arthritis are classic examples of such pathologies. As implied by its designation, the etiology of OJIA remains largely unknown. Genetic predisposition and possibly environmental factors may trigger the onset of an autoimmune response, possibly accompanied by the production of autoantibodies like rheumatoid factor and anti-cyclic citrullinated peptide antibodies . Autoantibodies may also be detected in sera obtained from PA patients, although the assessment of antibody titers is not a sensitive diagnostic tool . PA is considered an autoimmune disease developed by about a fourth of psoriasis patients, but little is known about the triggers of joint inflammation in individuals suffering from scaling cutaneous lesions. Psoriasis-associated skin lesions have been assumed to be provoked by dysregulation of immune cell function and cytokine release following trauma or infection. Cytokines may reach the skeleton and modify the function of cartilage- and bone-forming cells . RA is a type of sterile arthritis commonly triggered by previous genitourinary or gastrointestinal infection with Chlamydia trachomatis or enteric pathogens (e.g., Salmonella spp., Yersinia spp.), respectively . Streptococcus spp. and a wide variety of other bacterial pathogens may also provoke RA, particularly in genetically predisposed individuals. The preceding infection may or may not provoke clinical symptoms. In case it doesn't, the patient is generally diagnosed with undifferentiated arthritis, a clinically similar entity of unknown etiology. Of note, undifferentiated arthritis may also turn into polyarthritis. Indeed, oligoarthritis is characteristic of evolving polyarthritis. In this context, autoimmune disorders like rheumatoid arthritis, seronegative arthritis, and systemic lupus erythematosus as well as infectious diseases like Lyme disease and Whipple disease should be considered  . For detailed information on polyarthritis, the interested reader is referred to the respective article.
Although overall incidence and prevalence of oligoarthritis are unknown, the condition is presumably underdiagnosed. High prevalence of subclinical disease has been encountered in a study using sonography to examine both symptomatic and asymptomatic joints of school children in the United States . With regards to epidemiology, major difference between oligoarthritis and polyarthritis is the earlier age of onset of the former.
Additionally, epidemiological data can be provided regarding individual entities associated with this condition.
- Juvenile idiopathic arthritis is the most common rheumatoid disease among the pediatric population, although epidemiological data vary with geographic location. Lowest incidence rates have been reported for Asian populations, e.g., <1 per 100,000 children in Japan, and highest rates have been estimated for Europe, e.g., 23 per 100,000 in Norway . OJIA is among the most common forms of juvenile idiopathic arthritis and thus accounts for major shares of those values. Girls are affected significantly more often than boys. As per definition, symptom onset occurs in patients aged less than 16 years.
- The annual incidence of RA has been estimated to 10 per 100,000 adults, with approximately equal numbers of cases triggered by Chlamydia trachomatis and enterobacteria . Because pathogens triggering RA cannot be identified in all patients and because the condition may be self-limiting, true incidence rates are likely higher. A bimodal age distribution has been reported for post-streptococcal RA: Affected individuals are typically of age 8-14 or 21-37 .
- Psoriasis is a common disease and affects about 2% of the general population; about one-fourth of them develops PA, with men and women being affected equally . PA may manifest in form of polyarthritis (60%), oligoarthritis (30%) or distal interphalangeal arthritis (10%) . In most cases, skin lesions precede PA by about a decade. Thus, symptom onset would typically be expected to occur in patients aged 40 years and older. However, PA may also be diagnosed in people who have not yet developed cutaneous symptoms or in pediatric patients, in which case the designation psoriatic juvenile idiopathic arthritis is more commonly used. Of note, regional differences have been reported for this disease .
Pathophysiological events provoking oligoarthritis depend on the underlying disease. Still, dysregulation of immune cell function and cytokine release plays a crucial role in the induction and maintenance of oligoarthritis. On the one hand, immune-modulatory environmental influences may trigger the onset of OJIA in genetically predisposed individuals . Distinct populations of immune cells, e.g. T lymphocytes, plasma cells and natural killer cells, may be affected. On the other hand, psoriasis is associated with an activation of dendritic cells in the skin . These cells release interferon-α, a cytokine that promotes a determined subpopulation of dendritic cells to migrate to the lymph nodes. Here, they release interleukin-12 and -23, which affect T cell differentiation and maturation. Eventually, differentiated T cells return to circulation, reach end organs and produce tumor necrosis factor-α, interferon-γ, and interleukin-17, among others. In patients suffering from RA, the immune response triggering the onset of joint inflammation takes place in affected joints. In detail, antigens may spread via the cardiovascular system, reach joints, and induce an immune reaction associated with damage to anatomic structures composing the joint.
Further research is required to clarify the pathogenetic differences between distinct forms of juvenile idiopathic arthritis, to ascertain why psoriasis patients do or don't develop arthritis, and which conditions predispose for RA. Finally, there is a considerable overlap between these entities, since patients may develop psoriatic juvenile idiopathic arthritis and because determined forms of juvenile idiopathic arthritis predispose for RA. The central role of cytokines in all these pathologies is best illustrated by the patients' response to immunomodulatory therapy.
Specific measures can be recommended only for determined forms of oligoarthritis. RA, for instance, is triggered by an infection with Chlamydia trachomatis or enteric pathogens. Accordingly, measures to prevent sexually transmitted diseases and an appropriate general hygiene may reduce the individual risk of RA.
Oligoarthritis is a descriptive term referring to the simultaneous inflammation of two to four joints in an individual patient. In contrast, individuals suffering from an inflammation of a single joint are diagnosed with monarthritis, and those presenting with even more extensive joint diseases receive a diagnosis of polyarthritis. Distinction between monarthritis, oligoarthritis and polyarthritis may be of diagnostic value. For instance, traumatic joint injury is generally restricted to a single joint or to a determined region of the human body, e.g., the patient's feet or knees, as opposed to systemic autoimmune disease, metabolic disorder or nutrient deficiency, which rather manifest in form of multiple joint lesions. However, these are not exclusion criteria for either form of arthritis. In fact, both monarthritis and polyarthritis may turn into oligoarthritis upon an exacerbation or partial remission, respectively, and vice versa. Thus, it is strongly recommended to consider common causes of monarthritis or polyarthritis when dealing with a patient suffering from oligoarthritis. Anamnestic data, distribution patterns, and clinical symptoms not related to joint inflammation are of utmost importance at the time of establishing a list of potential differential diagnoses.
It is beyond the scope of this article to discuss every possible trigger of oligoarthritis. Thus, general information is provided wherever possible. Additionally, more detailed data are included regarding oligoarticular juvenile idiopathic arthritis (OJIA), reactive arthritis (RA), and psoriatic arthritis (PA), which are common causes of oligoarthritis.
Oligoarthritis refers to the simultaneous inflammation of two to four joints in an individual patient. Oligoarthritis may affect people of any race, both genders and all age groups, but diseases triggering multiple joint inflammation are generally more or less prevalent in determined patient groups. In pediatric patients, the most common cause of oligoarthritis is a specific form of juvenile idiopathic arthritis. However, children may also develop joint inflammation within two months after a genitourinary or gastrointestinal infection, and this form of arthritis is deemed reactive arthritis. The latter may also occur in adults. Furthermore, adult patients with a medical history of psoriasis may be diagnosed with psoriatic arthritis. In sum, a wide variety of autoimmune disorders, infectious diseases, metabolic and endocrine dysbalances as well as neoplasms may provoke oligoarthritis.
Symptoms characteristic of oligoarthritis are joint pain and tenderness of surrounding tissues, joint swelling, stiffness and reduced motion ranges. In severe cases, joint inflammation may provoke permanent deformities. Depending on the underlying disease, patients may show distinct distribution patterns and additional symptoms, and the treating physician will consider all this information when making a diagnosis and choosing an appropriate therapy.
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