Polyarticular Arthritis


Article Author:
Hossein Akhondi


Article Editor:
Nagendra Gupta


Editors In Chief:
David Wood
Andrew Wilt
Hajira Basit


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
6/4/2019 7:40:51 PM

Introduction

Clinicians frequently encounter patients with a complaint of "all my joints hurt." Although many physicians get excited about diagnosing a rare or unusual disease entity in such patients; in reality, many of these patients have either transient self-limiting or non-significant problems. The art of history taking and physical examination should narrow the broad differential diagnosis of polyarticular arthritis to a manageable few, and then confirmatory tests should prove or rule out the exact etiology. Although blood work, different imaging modalities, tissue biopsy, advanced diagnostic techniques are all available; the one thing that truly helps with diagnosis is precise and detailed questioning and physical examination, which also prevents wasting health care dollars for extensive and expensive workups.

The first order of evaluation is to see if the inflammation is from the joint or from an area next to it. Non-articular and peri-articular pain are common and confusing, and they radiate to the joint frequently. If the inflammation and pain are indeed from inside the joint, it can either be inflammatory or non-inflammatory. Non-inflammatory etiologies such as osteoarthritis (OA) are usually chronic and mild and don't have the prominent inflammatory changes such as redness, warmth, swelling, and generalized body disturbances. If the picture is inflammatory, then the clinician will confirm it with tests and make a differential diagnosis based on the number, pattern, chronicity, and symmetry of joints involved.[1]

Etiology

Non-articular etiologies: hypothyroidism, depression, somatoform pain disorder

Peri-articular etiologies: bursitis, tendinitis, neuropathic pain, metabolic bone diseases, soft tissue injury, fibromyalgia 

Non-inflammatory articular etiologies: osteoarthritis

Inflammatory arthritis etiologies:

1) Bacterial (Lyme disease, endocarditis, septic arthritis)

2) Viral (hepatitis B and C, Epstein Barr virus, parvovirus, dengue, alphaviruses, rubella, human immunodeficiency virus, mumps, coxsackievirus) 

3) Collagen-vascular disease (rheumatoid arthritis, palindromic rheumatism, rheumatic fever, lupus, vasculitis, systemic sclerosis, myositis, ankylosing spondylitis, psoriatic arthritis, Behcet syndrome, relapsing polychondritis)

4) Crystal-induced arthritis (uric acid deposition of gout, calcium pyrophosphate deposition of pseudogout)

5) Post-infectious or reactive arthritis (post enteric infections, disseminated gonococcal infection)

6) Familial Mediterranean fever  

Epidemiology

Data published by arthritis foundation in 2015 suggests that there are over 100 types of arthritis. And about 91.2 million adults either have physician-diagnosed arthritis and/or report joint symptoms consistent with a diagnosis of arthritis.[2] That translates to almost 1 in 3 persons aged 18-64. After the age of 65, half the men and two-thirds of women have arthritis. The incidence is on the rise, and Hootman estimates that by 2040, almost half the population will have physician-confirmed arthritis.[3]

Arthritis, and polyarticular arthritis, in particular, are more common in females and obese patients. Age significantly increases the prevalence. One estimate puts the total costs related to arthritis (medical care, earning losses, lost time, etc.) at 1% of US gross domestic product ($304 billion) for the 2013 fiscal year.[4]

Among people with arthritis, 33% have depression or anxiety, 25% have cardiac problems, 20% have respiratory conditions, and 16% have Diabetes. It is likely that arthritis is predisposing patients to all the comorbidities through physical inactivity. 

Pathophysiology

Pathophysiology of non-inflammatory arthritis is primarily mechanical but introduced cellular and biochemical processes will also change the normal slow cartilage remodeling process. There will be excess degeneration, less regeneration, and abnormal separation of the cartilage. Progressive cartilage loss, increased thickness of the subchondral plate, and cyst formation will happen. With time the cartilage gets thinner, looser, and weaker; bone will rub against bone causing remodeling of the bone and new bone formation at joint margins (osteophytes). Friction will cause mild inflammation.[5] All these changes will make the normal movement and gliding of bones over each other with the cartilage help more difficult and uncomfortable, and eventually painful. 

Pathophysiology of inflammatory arthritis can be infectious, crystal-induced, reactive, or autoimmune. In collagen vascular etiologies, inflammatory cytokines and autoantibodies create an inflammation cascade and pannus formation which can invade the cartilage and bone, and damage them. This damage is more acute and severe, and absent immediate medical attention, joint destruction can progress quite rapidly.

History and Physical

Acute arthritis usually lasts from hours to two weeks. Chronic arthritis is an inflammation of over two weeks. Chronic symptoms can be intermittent or constant. Symmetry and the number of joints involved are important factors. Pauciarticular is two to four involved joints whereas polyarticular is over five involved joints. Size and kind of the joints matter. Inflammatory pattern versus the non-inflammatory pattern, as mentioned, is a huge dividing factor.

Rheumatoid arthritis is usually polyarticular and in hands/wrists (small joints) in a symmetric distribution. It starts slow and lasts weeks to months before we make the diagnosis. Seronegative spondyloarthropathies are usually pauciarticular with axial involvement and large joint inflammation.[6] Osteoarthritis is in weight-bearing joints, is mostly asymmetric, and is worse with movement and better with rest.[7] Inflammatory arthritis is symmetric with severe inflammatory patterns and in non-weight-bearing joints. Morning stiffness of over than an hour is pathognomonic of inflammatory arthritis such as seronegative spondyloarthropathies.

An acute presentation with a migratory pattern can be viral arthritis, rheumatic fever or disseminated gonococcal infection; although viral arthritis is much more common than either of them.[8] It is hard to prove a diagnosis of viral arthritis as the inflammation usually resolves before confirmatory diagnosis. Septic joints are generally a straightforward diagnosis with hot, swollen, red, painfully moved joints. They are typically monoarticular arthritis of a large joint and come with constitutional symptoms and rarely come in a polyarticular form. More common would be an acute infection of a joint already affected by a polyarticular process. That makes the distinction difficult.  

The pain of osteoarthritis gets worse with movement and less with rest which is the opposite of rheumatoid arthritis that is worse with inactivity (morning stiffness) and better with movement. Short periods of synovitis (4-6 weeks) are usually from viral infections as opposed to longer periods that show an underlying persistent problem. Sensory problems like paresthesia, allodynia, anesthesia indicate a neuropathy or radiculopathy. Finally, the extra-articular symptoms can be hugely helpful and make or break the diagnosis — rashes (psoriatic arthritis), oral and genital lesions (Behcet syndrome), heart murmur (endocarditis), dry mouth and eye (Sjogren syndrome) and polyserositis (lupus).

Physical examination proves or disproves synovitis and sometimes shows the chronic changes of long-standing arthritis. The clinician should examine muscles, joints, tendons, bursas, and soft tissue. One should test both passive and active range of motion (ROM). Non-articular diseases present with normal passive ROM but reduced active ROM. Tendinitis or bursitis are good examples. Palpation can further differentiate these two. Bursitis has a very localized tender area that does not change much with movement, but the tender area in tendinitis is worse with movement. Articular diseases cause both reduced active and passive ROM. 

Warmth, redness, swelling, tenderness are the cardinal signs of inflammation and make the diagnosis of inflammatory arthritis easy to make. Septic arthritis has all these in a more pronounced form. Crepitation of the joint shows possible osteoarthritis and laxity prove a damaged and unstable joint. Again, extra-articular findings in the physical exam are sometimes even more crucial than the findings of the joints.

Evaluation

Laboratory Work

Evaluation of poly-arthritis can be extensive.

Rheumatological workup usually recommended includes: Rheumatic factor (RF) and anti-citrullinated peptide antibodies (CCP) for rheumatoid arthritis (RA), antinuclear antibody (ANA) for systemic lupus erythematosus and some other entities, anti-smith and anti-double-stranded DNA for confirmation of lupus, anti-Scl-70 for systemic sclerosis, anti-Ro (SSA) and anti-La (SSB) for Sjogren syndrome, anti-U1-RNP for mixed connective tissue disease, anti-neutrophilic cytoplasmic antibody (ANCA) for granulomatosis with polyangiitis (C form) and microscopic polyangiitis (P form), Anti-Jo-1 for myositis, anti-histone for drug-induced lupus erythematosus, cryoglobulin for vasculitis and hepatitis C. 

Erythrocyte sedimentation rate and C-reactive protein are non-specific markers of inflammation but usually helpful in ruling in a pathology causing significant inflammation and also monitoring its response to treatment.[9]

Polarized microscopy of synovial fluid can help with crystal arthritis diagnoses, such as gout and pseudo-gout. Clinicians also analyze synovial fluid for cell count, gram stain and cultures. Synovial fluid leukocyte counts less than 200/mm are normal, between 200/mm and 2000/mm are associated with non-inflammatory arthritis, and over 2000/mm with inflammatory arthritis. If the cell count is over 50000/mm, physicians should treat the fluid as infectious.[10]

Work up should also rule out common infectious diseases that cause arthritis. We will achieve this with testing for hepatitis, Lyme disease, and parvovirus. 

Imaging Studies

Imaging is a costly proposition and has a low diagnostic yield. There are usually no positive findings in the cases of acute polyarthritis. There is also no need to do imaging of every single joint involved. Some joints are "high yield" and provide information essential for diagnosis and treatment; some other joints are not. 

X-rays are helpful in showing fractures, dislocations, and osteomyelitis. In advanced osteoarthritis, the x-rays are useful and show erosion, sclerosis, joint space narrowing, osteophyte formation; but usually by the time these changes are present, the disease is well advanced and easily recognizable from history and physical. Also, many aging patients have x-rays compatible with osteoarthritis without having clinical symptoms; therefore, the correlation can be tricky. Although hand, wrist and metacarpal x-rays are unnecessary for a diagnosis of RA, they occasionally do help, and the response to treatment is at times monitored based on findings on x-rays. Cervical X-rays (specifically the C1-2) is essential during follow up of RA to look for damages and help prevent a pathologic fracture of the joint which would be devastating.[11] X-rays also easily show the disposition of calcium pyrophosphate in joints, such as a knee, and make the diagnosis of pseudo-gout. X-rays can show sacroiliac joint involvement of seronegative spondyloarthropathy although magnetic resonance imaging (MRI) is more sensitive.  

Ultrasound is readily available in the clinics and hospitals and is has utility for a variety of functions, but it has a limited role in polyarticular arthritis for detecting erosions and synovitis. Clinicians can easily perform joint injection under the guidance of ultrasound.[12][13] Computed tomography has almost no role other than ruling out other etiologies, and the role of MRI is to pick very early joint inflammation or early bone/soft tissue infection. 

Radionuclide scans are rarely done but have specific purposes. Picking up metastases, Paget disease of the bone, and osteomyelitis represent several of these indications.   

Biopsy

Biopsy many times have the final word; as is in most of medicine. There are enough diagnostic modalities for polyarticular arthritis to render biopsy unnecessary, but still, biopsies are occasionally done to diagnose or confirm a clinical suspicion for different vasculitis, arteritis, infectious etiologies, or granulomatous diseases.

Treatment / Management

Diagnosis Dictates Treatment

For osteoarthritis: Correction of the biophysical abnormality, weight loss, reduction of joint stress, maintenance of heat and warmth, strengthening exercises, non-steroidal anti-inflammatory medication (NSAIDS), injection of corticosteroids, are all helpful in that sequence. Joint replacement therapy will have the final word.

For collagen vascular diseases: Biologic medication and anti-inflammatories are in use and have revolutionized the management of diseases that in the past used with gold salts as a treatment! Half a century ago, there was a therapeutic pyramid for rheumatisms that would start with NSAIDs and escalate to steroids and then penicillamine and gold salts for refractory cases. Such an approach would permit joint destruction to advance before any real attempt at treatment was initiated. Nowadays, the pyramid is reversed, and early aggressive treatment with biologic medication can prevent joint damage at an early stage.

Rheumatologists use NSAIDs as a palliative measure for advanced disease and significant damage before they consider surgical approaches. Many new biologic agents are in the market and used in oral or injectable forms for a variety of approved indications.  

For infections: Antibiotic Treatment

For crystal-induced arthritis: Chelating agents are the treatment of choice. They will reduce the level of an offending agent in blood and prevent further damages.

Differential Diagnosis

The differential diagnosis is broad, but the following common conditions need to be ruled out:

  • Psoriatic arthritis
  • Tophaceous Gout
  • Undifferentiated seronegative polyarthritis
  • Erosive inflammatory arthritis
  • Enteropathic arthritis
  • SLE
  • Scleroderma
  • Polymyalgia rheumatica

Prognosis

Prognosis depends on several factors:

Duration of symptoms, age at onset, male gender, Obesity, the number of joints involved, lower limb involvement, severity of inflammation, and elevated lab markers of inflammation.

Complications

Complications are many. Each disease can induce its own set of complications based on the severity of the pathology, location of inflammation, host factors, and treatments available. 

Deterrence and Patient Education

There are many resources available to the patients. Arthritis is a prevalent disease and has sparked a lot of interest. Arthritis Foundation, Mayo Clinic, and Johns Hopkins medical system (amongst others) have all resources for virtually every aspect of the disease for the patients. From information regarding the disease itself to tips for managing pain and disability, nutrition, rehabilitation, the role of exercises, the role of yoga, different aspects of medical treatment, different treatment available, side effect profile of each medication.

Enhancing Healthcare Team Outcomes

Management of polyarticular arthritis is indeed a collaborative effort. Primary care physicians, nurses, pharmacists, rheumatologists, orthopedic surgeons, neurologists, physical and occupational therapist, radiologists, pathologists, many other subspecialists, and rehabilitation doctors are all involved in the process, and each contributes to diagnosis and management. Each focuses on their area of expertise and relay the relevant information to all the others in the team. Individualized input and management in the setting of a problem that can originate from a variety of different pathologies are limited and misleading. 


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Polyarticular Arthritis - Questions

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A female patient has an 8-week history of symmetrical small joint polyarthritis. She has had some improvement on naproxen 500 mg twice a day. She continues to have problems making a fist, has missed work, and still has swelling of several metacarpal phalangeal and metatarsal phalangeal joints. Which of the following would not be helpful in establishing the diagnosis?



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A 14-year-old male is brought to the office with complaints of bilateral wrist, elbow, and knee pain. He has had intermittent fevers and an evanescent rash. The patient lives in Wisconsin and is a boy scout. He has no past medical history or medications other than ibuprofen. Which of the following would not be part of the differential diagnosis?



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A 35-year-old female presents with 3 months of joint pain. Initially, the pain was in her feet but then moved to her hands and wrists. She reports morning stiffness and 4/10, constant, dull pain in her hands and wrists bilaterally for several hours a day. The pain is worse when she wakes up and better after moving around for an hour or two. She otherwise is healthy and takes a vitamin supplement daily. On physical exam, she has signs of synovitis in a total of seven metacarpophalangeal and proximal interphalangeal joints bilaterally. There are no signs of synovitis in her feet. What diagnostic test should be done next?



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A 26-year-old male from India is in the United States to visit his family. He reports that he had a cold while in India 2 weeks ago but got better and now is experiencing high fever, severe arthralgia, and arthritis in over ten joints. The arthritis is bilateral and symmetric and involves the distal joints of all limbs. He complains of a headache and diffuse myalgia. The physical exam reveals a maculopapular rash without any hemorrhagic sites. Bloodwork shows a normal platelet count, lymphopenia, normal liver functions tests, and positive hepatitis B surface antibody (anti-HBs). What is the most likely diagnosis?



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A 70-year-old female from West Africa is visiting the United States. She has a history of hypertension and diabetes, with reasonable control of both with metformin and lisinopril. She was fine during the visit when she suddenly started to have a high fever. Joint pain started two days later. Hands, wrists, ankles, and back all are painful. Pain is sharp, 4/10, worse with movement, remitting and relapsing at different times with no exact timing. When the ankle pain is better, the wrists hurt more and if everything else is good, then the back bothers her. Pain affects mobilization. The physical exam confirms arthritis and also shows a diffuse maculopapular rash on limbs and trunk. Blood work shows lymphopenia, thrombocytopenia, and mild liver function test elevation at 1.5 times normal values. Which one of the following is the best approach to this patient?



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A 27-year-old male is being investigated for joint pain of several months duration. He also has fatigue, anorexia, headache, and neck stiffness for the past few months. His wrist and fingers were painful a few weeks ago, but they recently got better. He attributes this to his job as a hunter in the woods. Over time, his knees have become painful too. He has been otherwise healthy but does remember seeing a rash on his trunk several months ago that disappeared without a problem. His wife, who is accompanying him thinks that "he has not been himself recently." Vital signs and physical examination are unremarkable other than the presence of arthritis in both knees. The patient is alert and oriented to time and place, but at times, asks questions that are not relevant to the conversation. Which of the following is the next step in the management of this patient?



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Polyarticular Arthritis - References

References

Murphy LB,Sacks JJ,Helmick CG,Brady TJ,Barbour KE,Hootman JM,Boring MA,Moss S,Guglielmo D,Theis KA, Arthritis prevalence: which case definition should be used for surveillance? Comment on the article by Jafarzadeh and Felson. Arthritis     [PubMed]
Jafarzadeh SR,Felson DT, Updated Estimates Suggest a Much Higher Prevalence of Arthritis in United States Adults Than Previous Ones. Arthritis     [PubMed]
Pujalte GG,Albano-Aluquin SA, Differential Diagnosis of Polyarticular Arthritis. American family physician. 2015 Jul 1     [PubMed]
Murphy L,Helmick CG, The impact of osteoarthritis in the United States: a population-health perspective: A population-based review of the fourth most common cause of hospitalization in U.S. adults. Orthopedic nursing. 2012 Mar-Apr     [PubMed]
Goldring SR,Goldring MB, Changes in the osteochondral unit during osteoarthritis: structure, function and cartilage-bone crosstalk. Nature reviews. Rheumatology. 2016 Nov     [PubMed]
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Li R,Hatcher JD, Gonococcal Arthritis null. 2018 Jan     [PubMed]
Pereira D,Ramos E,Branco J, Osteoarthritis. Acta medica portuguesa. 2015 Jan-Feb     [PubMed]
Meng G,Zhu Q,Shao J,Zhang Q,Liu L,Wu H,Xia Y,Bao X,Gu Y,Wang H,Shi H,Sun S,Wang X,Zhou M,Jia Q,Wang G,Song K,Wu Y,Niu K, Comparing the diagnostic ability of inflammatory markers in metabolic syndrome. Clinica chimica acta; international journal of clinical chemistry. 2017 Dec     [PubMed]
Oliviero F,Galozzi P,Ramonda R,de Oliveira FL,Schiavon F,Scanu A,Punzi L, Unusual Findings in Synovial Fluid Analysis: A Review. Annals of clinical and laboratory science. 2017 May     [PubMed]
Hassan S, Overview of musculoskeletal ultrasound for the clinical rheumatologist. Clinical and experimental rheumatology. 2018 Sep-Oct     [PubMed]
Mitran C,Barbulescu A,Vreju FA,Criveanu C,Rosu A,Ciurea P, Musculoskeletal Ultrasound in Early Rheumatoid Arthritis - Correlations with Disease Activity Score. Current health sciences journal. 2015 Jul-Sep     [PubMed]
Ibrahim M,Suzuki A,Yamada K,Takahashi S,Yasuda H,Dohzono S,Koike T,Nakamura H, The relationship between cervical and lumbar spine lesions in rheumatoid arthritis with a focus on endplate erosion. Journal of spinal disorders     [PubMed]

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