Symptoms of polyarthritis are those of arthritis affecting five or more joints. Frequent complaints are:

• Tenderness
• Arthralgia
• Joint swelling
• Joint effusion
• Joint deformity
• Stiffness
• Reduced motion range
• Crepitation

Affected joints may be in close proximity to each other or may be located in distant parts of the human body. In fact, many forms of polyarthritis compromise several joints of both hands or feet. The above listed symptoms and signs may not be noted at all times; they are likely to diminish or worsen with rest or exercise. Patients suffering from inflammatory polyarthritis may additionally report fatigue, fever, night sweats, weight loss and lymphadenopathy.

Every form of polyarthritis may severely affect the patient's ability to cope with everyday tasks.

Anamnestic data and results of physical examination should allow for the treating physician to answer the following:

• Affected joints: hands, feet, limbs, axial involvement
• Symmetrical or asymmetrical polyarthritis
• Acute or chronic disease
• Intermittent or constant complaints
• Progressive or non-progressive course of the disease
• Extra-articular symptoms

Moreover, it is important to distinguish between inflammatory and non-inflammatory forms of polyarthritis. This may be achieved by assessing inflammatory markers like serum levels of C-reactive protein and the erythrocyte sedimentation rate. Both positively correlate with inflammation.

All these data should be considered when compiling a list of differential diagnoses and deciding on a target-oriented diagnostic approach [1]. They do not yet allow for a definitive diagnosis and additional measures are required to confirm a suspicion.

• Since many forms of polyarthritis are autoimmune-mediated, the presence of autoantibodies should be evaluated. Traditionally, rheumatoid factor and anti-cyclic citrullinated peptide antibody concentrations are assessed, but recent publications encourage to measure anti-carbamylated protein antibody levels, too, if RA is suspected [10]. Ascertainment of antinuclear antibodies is a very sensitive but little specific approach to SLE diagnosis.
• Hemogram and blood chemistry may provide important information with regards to hematological anomalies.
• Blood cultures, detection of pathogenic nucleic acids in blood samples by means of molecular biological techniques and serological tests are indicated if an infectious polyarthritis is suspected.
• Pathogens may also be isolated from synovial fluid specimens, and cytologic and biochemical analysis of such samples may reveal further clues as to the underlying pathology.
• Diagnostic imaging is often performed to assess the condition of the affected and apparently unaffected joints as well as the skeleton in general. Magnetic resonance imaging allows for a more detailed evaluation of cartilage damage than plain radiography.

Measures described herein typically reveal the following in case of RA, SNA and SLE:

• RA: symmetrical involvement of joints of hands and/or feet, chronic disease, constant complaints albeit with matutinal exacerbation, slowly progressive course, possibly inflammation of cutaneous, cardiac, pulmonary and ocular tissues, elevated concentrations of inflammatory markers, rheumatoid factor and/or anti-cyclic citrullinated peptide antibody positive [11]
• SNA: rheumatoid factor negative, otherwise any combination of symptoms and signs, e.g., seronegative RA manifests as described previously except for the result of the measurement of rheumatoid factor
• SLE: symmetrical polyarthritis preferentially affecting interphalangeal joints, chronic disease, disease course marked by remission and relapse, malar rash, inflammation of cardiac, pulmonary and renal tissues, elevated levels of inflammatory markers, antinuclear antibodies positive, possibly anemia, leukopenia and thrombocytopenia

If at all possible, causative treatment should be applied to cure the underlying disease. Unfortunately, causative treatment is not available for many forms of polyarthritis and only supportive therapy can be provided. In any case, therapy should be adjusted to the individual case, to present complications and comorbidities, to the patient's response to therapy, possible side effects and adverse events. The following treatment options may be considered:

• Rest
• Cold and heat
• Physical therapy in order to maintain or regain motion ranges
• Dietary and lifestyle adjustments, e.g., weight loss, avoidance of triggers of recurrence
• Analgesia, primarily achieved by application of paracetamol, metamizol or opioids and derivatives
• Anti-inflammatory therapy to reduce arthritis and inflammatory pain, with non-steroidal anti-inflammatory drugs and corticosteroids being most frequently administered
• Further immunosuppressive treatment and application of disease-modifying antirheumatic drugs, e.g., hydroxychloroquine, methotrexate, sulfasalzine, cytokine blockers like abatacept and rituximab
• Intraarticular injection of hyaluronic acid [12]

This list is restricted to treatment options for articular manifestations of polyarthritis. Many diseases that cause polyarthritis are associated with extra-articular symptoms, e.g., myocarditis, pleuritis and nephritis, and these conditions require an appropriate management as well.

The patient's prognosis largely depends on the cause of polyarthritis.

• Long-term immunosuppressive therapy is generally required to relieve symptoms associated with autoimmune-mediated polyarthritis, and such treatment may have side effects. With regards to RA, patients who test positive for rheumatoid factor are generally expected to develop more severe extra-articular complications than those who are diagnosed with seronegative RA or SNA [8]. SLE is a potentially life-threatening disease, but mortality has been diminished during the last decades. Nowadays, 5-, 10-, and 15-year survival rates are 96%, 93% and 76%, respectively [9].
• Although many infectious diseases that may trigger polyarthritis are curable, patients developing such conditions are often immunocompromised and severe immunodeficiency may negatively affect the outcome.

Polyarthritis results from pathophysiological events that simultaneously take place in several joints of the body. In general, joints are susceptible to virtually all kinds of disturbances, e.g., to malfunction of the immune system, infection with pathogens and release of toxins, interruption of blood supply, nutrient deficiency and metabolic perturbances, carcinogenic stimuli, and trauma. Only in case of generalized disease, polyarthritis may develop. In this context, generalized may refer to systemic diseases, hematogenous or lymphogenous spread of pathogens or tumor cells. With regards to the aforegiven list, compromise of five or more joints is more likely if a patient suffers from autoimmune diseases, nutrient deficiencies and metabolic disorders. In contrast, vascular events, neoplasms and traumas commonly affect one or few joints. This classification is not irrefutable though: RA may manifest in form of monarthritis and polyarthritis may be part of a paraneoplastic syndrome [3] [4].

In detail, the following diseases may be associated with polyarthritis [1]:

• Autoimmune disorders: RA, SNE, SLE, ankylosing spondylitis, Behcet's syndrome, fibromyalgia, inflammatory bowel disease, psoriatic arthritis, polymyalgia rheumatica, polymyositis, Reiter's syndrome, Sjogren's syndrome, Wegener granulomatosis
• Infectious diseases
  
  • Infection with bacteria, e.g., Borrelia burgdorferi (Lyme disease), Brucella spp. (brucellosis), Mycobacterium tuberculosis (tuberculosis), Neisseria gonorrhoeae (gonorrhea), Neisseria meningitidis (meningococcemia), Staphylococcus aureus, Streptococcus spp., Tropheryma whipplei (Whipple disease), other pathogens associated with bacterial endocarditis
  • Infection with viral pathogens, e.g., Barmah virus (Barmah Forest virus infection), Chikungunya virus (Chikungunya fever), Mayaro virus (Mayaro-Semliki Forest virus disease), Ross River virus (Ross River fever), Sindbis virus (Sindbis virus infection) and other alphaviruses, hepatitis B and C viruses (hepatitis B, hepatitis C), human parvovirus B19, rubella virus (rubella) [5]
• Metabolic disorders: amyloidosis, gout, hyperparathyroidism, hyperthyroidism, hypothyroidism
• Neoplasms: multiple myeloma, metastatic cancer, paraneoplastic fasciitis and polyarthritis syndrome [4]
• Degenerative/idiopathic: osteoarthritis, sarcoidosis

Due to the large number of differential diagnoses, epidemiological data regarding the overall incidence and prevalence of polyarthritis cannot be provided. Similarly, underlying disorders vary largely with respect to racial and gender predilection and age distribution. In general, patients of all races, both genders and all age groups may develop polyarthritis.

• RA is a common disease affecting up to 1% of the population, with women being significantly more susceptible than men. RA is typically diagnosed in the elderly. Juvenile rheumatoid arthritis, also referred to as juvenile idiopathic arthritis, constitutes a different entity. Here, symptom onset occurs during the first two decades of life.
• SLE has recently been reported to affect about 0.1% of the US-American population [6]. Similarly to RA, women have been shown to be more prone to SLE than men. Symptom onset may occur at any age.

Furthermore, risk groups may be defined for determined forms of polyarthritis. In this context, any condition associated with immunosuppression, e.g., diabetes mellitus, infection with human immunodeficiency virus and immunosuppressive treatment, may predispose for infectious polyarthritis. This also applies to behavior favoring infection with causative pathogens, e.g., men having sex with men and intravenous drug abuse.

Differences regarding the geographic distribution of polyarthritis is also best illustrated by those pathogens causing infectious polyarthritis: Hepatitis B is a major health concern worldwide, while the above described alphaviruses are prevalent only in determined countries [5].

A healthy joint is formed by at least two bones whose articulating surfaces are able to move virtually frictionless against each other, whereby the joints' motion ranges differ largely. Most joints of the human body are synovial joints, i.e., the respective articulating surfaces are covered by smooth hyaline cartilage and synovial tissue that is further lubricated by synovial fluid contained in the synovial cavity, and the whole joint is surrounded by a fibrous joint capsule. Every process altering the properties of those joint-composing structures may provoke arthritis, and such processes may originate from articular or extra-articular events:

• Immune reaction against joint tissues
• Articular deposition of immune complexes
• Pathogen-mediated cell lysis
• Release of toxins
• Release of pro-inflammatory mediators
• Infiltrating inflammatory cells
• Cellular hyperplasia
• Tumor growth
• Degenerative changes
• Traumatic destruction of cartilage or underlying bone

In most cases, these pathophysiological events are mutually dependent. For instance, chronic, inflammatory polyarthritis is generally associated with excess release of pro-inflammatory cytokines interleukin-1β, tumor necrosis factor-α and transforming growth factor-β by synovial cells, infiltration of inflammatory cells that further stimulate inflammation, and proliferation of synovial tissue [7].

In general, lifestyle decisions consistent with an overall good health, i.e., regular, moderate exercise, appropriate nutrition and maintenance of a healthy body weight contribute to joint health. Measures to prevent infectious diseases possibly associated with polyarthritis are also recommended and may comprise use of repellents, acaricides and insecticides, as well as safer sex.

As per definition, polyarthritis may be diagnosed if a patient presents with five or more inflamed joints [1]. In contrast, patients showing an inflammation of two to four joints suffer from oligoarthritis, whereas other diseases only affect one single joint and cause monarthritis [2].

In general, arthritis manifests in form of arthralgia, joint swelling, reduced motion ranges and possibly crepitation. This also applies to polyarthritis, a condition that is easily diagnosed based on anamnestic data and results of physical examination. However, there is an extensive list of differential diagnoses underlying polyarthritis and often, considerable efforts are required to identify the primary disorder and to choose an appropriate treatment. Polyarthritis may be the result of a myriad of generalized disorders, e.g., of autoimmune diseases, infection, endocrinologic imbalances, and, less frequently, metastatic neoplasms. As opposed to monarthritis, traumatic lesions of five or more joints are rare.

This article aims at providing information about a general approach to polyarthritis, since it is beyond its scope to discuss clinical presentation, diagnostic workup and treatment of any one differential diagnosis. The interested reader is thus referred to the respective articles. In order to illustrate the broad spectrum of diseases possibly associated with polyarthritis, rheumatoid arthritis (RA), seronegative arthritis (SNA) and systemic lupus erythematosus (SLE) shall serve as examples in determined sections of this review.

• RA is one of the most common joint diseases. Affected individuals suffer from chronic, symmetrical polyarthritis. Extra-articular symptoms are less frequently observed than in patients diagnosed with SLE, but may affect skin, cardiovascular system, lungs and eyes.
• SNE comprises seronegative RA, seronegative spondyloarthropathies and, in the broader sense of the word, all forms of autoimmune-mediated polyarthritis if the affected individual tests negative for the autoantibody rheumatoid factor.
• SLE is an autoimmune disorder mainly characterized by cutaneous lesions. These are provoked by deposition of immune complexes in small vessels. SLE may be associated with polyarthritis, and patients may also suffer from central nervous system, cardiac, pulmonary and renal compromise.

Polyarthritis is diagnosed if a patient presents with five or more inflamed joints. This condition is typically associated with joint pain, joint swelling, joint deformity, stiffness and reduced motion ranges. The skin surrounding the affected joints may be tender and reddened.

Polyarthritis may develop within the scope of a wide variety of disorders, and the aforementioned symptoms are very unspecific. Primary diseases that may be associated with polyarthritis are rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease and psoriasis - all of which are provoked by an immune reaction against the body's own tissues -, infectious diseases like Lyme disease, hepatitis B, hepatitis C and tuberculosis, as well as thyroid disorders and cancer.

Distinct parameters will be evaluated in order to identify the underlying disorder and to choose an adequate therapeutic approach. Important clinical data are relate to the course of the disease, to affected joints, the presence of inflammation and extra-articular manifestations. Treatment may comprise dietary and lifestyle adjustments, physical therapy and medication.

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