It is a chronic systemic inflammatory disease of undetermined etiology involving primarily the synovial Acute monoarticular Inflammatory Septic Arthritis Gout Pseudogout
Non-inflammatory Trauma Hemarthrosis
Chronic monoarticular Inflammatory Chronic infectious arthritis Lyme disease
Crystalline synovitis Pauciarticular juvenile RA Non-inflammatory Osteoarthritis
Ischemic necrosis Hemarthrosis
Paget disease involving the joint Synovial osteochondromatosis
Acute polyarticular Inflammatory Rheumatic fever
Gonococcal arthritis Polyarticular gout Polyarticular pseudogout
Viral arthritis (hepatitis B, parvovirus B-19) Bacterial endocarditis
Rheumatoid arthritis and still disease Systemic lupus erythematosus Reactive arthritis and Reiter syndrome Acute sarcoid arthritis and mediterranean fever, Familial enteropathic arthropathies
Chronic polyarticular Inflammatory Rheumatoid arthritis
Systemic lupus erythematosus Viral arthritis and psoriatic arthritis Reactive arthritis and Reiter syndrome Enteropathic arthropathies and Behçet disease Ankylosing spondylitis and undifferentiated Spondyloarthropathy noninflammatory Non-inflammatory Osteoarthritis hemochromatosis
Ochronosis hypertrophic pulmonary osteoarthropathy amyloidosis Acromegaly
Symmetric arthritis is seen in Rheumatoid arthritis, in some Psoriatic arthritis, Parvovirus infection, SLE.
Character Normal Noninflammatory Inflammatory Infectious
WBCs/mm3 <200 200-3,000 3,000-50,000 >50,000
%PMNs <25 <25 >50 >75
Color Clear Xanthochromic Yellow Opaque
Differential None Osteoarthritis, RA, gout*, Bacterial, TB
scleroderma, SLE, pseudogout, asceptic necrosis psoriatic arthritis,
ankylosing spondylitis, SLE JOINT ASPIRATION STUDY
*Sometime gout and pseudo gout may have >50,000 WBC/mm3.
membranes and articular structures of multiple joints. The hallmark feature of the disease is persistent symmetric polyarthritis (synovitis) that has potential to destroy cartilage and cause bone erosions and eventually deform the joint. RA seems to be associated with cigarette smoking.
T cells play the main role in pathogenesis and any disease or drug that negatively affects them may help relieve the symptoms of RA.
Juvenile rheumatoid arthritis (JRA) is the most common form of childhood arthritis. The cause remains unknown.
Clinical Features
Stiffness of joint and pain are the chief problems with which patient presents initially. He may also complain of constitutional symptoms like fatigue, malaise, and weight loss. RA typically involves small joints of hand.
Atlantoaxial subluxation may present with occipital headaches.
Sometimes patient may present when joint deformity is already visible. Long standing RA is one of the most common causes of amyloidosis. Various other features of RA that are caused due to extra-articular and systemic involvement are:
• Damage to the ligaments and tendons: This leads to severe deformity of joints.
– “Zig-zag” deformity: Combination of an ulnar drift of the fingers and carpal rotation. Radial deviation of the wrist with ulnar deviation of the digits.
– Boutonniere deformity: Nonreducible flexion at the proximal interphalangeal (PIP) joint along with hyperextension of the distal interphalangeal (DIP) joint of the finger.
– Swan-neck deformity: Hyperextension at the PIP joint with flexion of the DIP joint.
– Arthritis mutilans (opera glass hands): If destruction is severe and extensive, with dissolution of bone.
Phalanges may shorten and the joints may become grossly unstable. Pulling on the fingers during examination may lengthen the digit much like opening opera glasses, or the joint may bend in unusual directions merely under the pull of gravity.
• Rheumatoid nodules: They are most commonly found on extensor surfaces or sites of frequent mechanical irritation (olecranon process, back of heel, Achilles tendon). It is initial event caused by focal vasculitis.
Methotrexate may flare this process.
• Baker’s cyst: When the effusion of a joint is put under increased pressure with joint flexion, the synovium may be forced between articular structures and a
portion becomes trapped and separated from the rest of the joint, forming a Baker cyst. It often occurs fairly early in the course of the disease, with pain, edema, and inflammation in the posterior knee and calf.
• Cardiac involvement: Carditis, pericarditis.
• Pulmonary involvement: Pleuritis, intrapulmonary nodules, interstitial fibrosis (Caplan’s syndrome).
• Hepatic involvement: Hepatitis.
• Ocular involvement: Scleritis, episcleritis, dryness of the eyes (Keratoconjunctivitis sicca—in 25% of RA patients).
• Vascular involvement: Vasculitis (rheumatoid nodule).
• Neurological: Entrapment neuropathy (carpal tunnel syndrome) may result from synovitis about the flexor tendons. It is evinced by pain and/or paresthesias in the median nerve distribution of the hand, a positive Phalen and/or positive Tinel test, or positive electromyography. Radiculopathy is most common at the C2 root when cervical spine is involved.
‘99er’-Parvovirus infection: RA like symptoms with small joint involvement and weakly RF positive.
Diagnosis
The diagnosis is based on the use of clinical criteria; there is no single test or finding that will diagnose RA. The diagnosis typically is made when 4 of 7 qualifying criteria established by the American Rheumatism Association are met. These qualifying criteria are as follows:
• Morning stiffness lasting longer than 1 hour before improvement
• Arthritis involving 3 or more joints.
• Arthritis of the hand, particularly involvement of the proximal interphalangeal (PIP) joints, metacarpo-phalangeal (MCP) joints, or wrist joints.
• Bilateral involvement of joint areas.
• Positive serum rheumatoid factor (RF).
• Rheumatoid nodules.
• Radiographic evidence of RA (periarticular osteoporosis with erosions around affected joints).
The diagnostic criteria for JRA are onset occurring when younger than 16 years, persistent arthritis in one or more joints for at least 6 weeks, and exclusion of other types of childhood arthritis.
Treatment
RA flares or exacerbations (increased pain, edema, and dysfunction, high titers of RF) require rest, NSAIDs, DMARDs, short courses of prednisone (2-4 wk), and
possibly intra-articular steroid injections. DMARDs are indicated in erosive RA and also those who are steroid dependent. Methotrexate is initial DMARD of choice.
Patients presenting with mild RA are treated initially with NSAIDs, upon which hydroxychloroquine may be added if NSAIDs are not effective alone. Moderate to severe cases are treated with NSAIDs and methotrexate. If methotrexate fails or is contraindicated, than anti-TNF drugs like Infliximab, etanercept, etc. are used. Gold and immunosuppressants are the last resort if nothing works.
In RA patients with atlantoaxial subluxation (C1-C2).
any hyperextension of the neck may cause permanent damage to the spinal cord. Therefore RA patients before anesthesia or intubation must be screened for this with a plain X-ray (lateral neck and open mouth views). If there is evidence of subluxation, then stabilize the spine before the procedure.
‘99er’- Steroid therapy—give vitamin D3 and Ca2+ to prevent osteoporosis and do bone densitometry every year.
Felty syndrome: A triad of RA, neutropenia, and splenomegaly. Patients are prone to serious bacterial infections and this requires prompt diagnosis and initiation of antibiotic therapy.
Ruptured Baker cysts are often confused with deep vein thrombosis (DVT). The diagnosis is best made with ultrasonography. Treatment includes rest, elevation, needle puncture of the calf, knee joint aspiration, and referral.
Carpal tunnel syndrome treatment includes rest, temporary immobilization, NSAIDs, and surgery.
‘99er’-Carpal tunnel syndrome—Suspected when patient complains of pain/paresthesia when wrist joint is compressed and this is also the first step of diagnosis.
Tinel test (pain/paresthesia upon tapping radial nerve) and phalen maneuver (pain/paresthesia after 30-60 wrist flexions) are positive. Electrodiagnostic tests are confirmatory diagnostic modality. Most effective initial treatment is night time wrist splinting.
‘99er’-Adult Stills disease is a variant of rheumatoid arthritis which is seen in 20-30s age groups. Patient has high spiking fever, evanescent salmon color macular rash on trunks or extremity. Patient also has arthritis, arthralgia and leukocytosis. RF and ANA are negative. Liver failure is a serious problem in Stills disease patient who are taking NSAIDs. Therefore, LFTs should be monitored. NSAIDs, glucocorticoids and Methotrexate are the drugs used for treatment.
OSTEOARTHRITIS (OA)
Also known as degenerative arthritis, it is the most common joint disease which is a chronic process affecting articular
cartilage of synovial joints, particularly large weight-bearing joints (hip and knee). OA is a non-inflammatory disease, particularly common in older patients. OA can develop secondary to various causes like:
• Obesity (increased mechanical stress)
• Repetitive use
• Previous trauma (post-traumatic OA)
• Infection
• Crystal deposition
• Acromegaly
• Neuropathic disorder leading to a Charcot joint (syringomyelia, tabes dorsalis, diabetes)
• Previous rheumatoid arthritis (burnt-out rheumatoid arthritis)
• Heritable metabolic causes (alkaptonuria, hemochro-matosis, Wilson disease)
• Hemoglobinopathies (sickle cell disease, thalassemia)
• Underlying orthopedic disorders (congenital hip dislocation, slipped femoral capital epiphysis).
The most common joint to be affected is the knee. It is the leading cause of chronic disability in the elderly in the western world. The second most common site for OA is the thumb base.
Clinical Features
Deep, achy, joint pain exacerbated by extensive use and relieved by rest is the primary symptom. Also, reduced range of motion and crepitus are frequently present. Joint malalignment may be visible. Heberden nodes, which represent palpable osteophytes in the DIP are characteristic in women but not in men. They are known as Bouchard’s nodes when they are in PIP. Major joints involved in OA are hip, knee, and the small joints of the fingers (PIPs and DIPs). The joint involvement is very slow, progressive, and irreversible. Morning stiffness is always < 20-30 min.
Diagnosis
No laboratory studies can assist in diagnosis of OA per se.
All indices of inflammation like ESR are normal. Diagnosis is made on clinical and X-Ray findings.
X-ray: It shows osteophytes, subchondral sclerosis, and unequal and narrowed joint space.
Treatment Physical Therapy
Lifestyle modification, particularly exercise and weight reduction is a core component of the management of OA.
Correction of poor posture also helps.
Drug Therapy
No specific cure present. Only palliative therapy is used to relieve pain. The first drug to use for pain in OA is acetaminophen. It is reasonable to prescribe analgesic doses of NSAIDs if there is no relief with simple analgesics.
COX-2 inhibitors may be used in patients who are at high risk for GI complications.
Surgery
Orthopedic surgery and joint arthroplasty is reserved for cases in which aggressive medical treatment has been unsatisfactory and especially when patient’s quality of life has been decreased.
GOUT
Gout is a common disorder of uric acid metabolism that can lead to recurrent episodes of joint inflammation, tissue deposition of uric acid crystals [monosodium urate monohydrate (MSU) crystals] and joint destruction if left untreated. Gout is the most common crystal-induced arthritis.
Clinical Features
It initially presents as acute monoarticular arthritis with podagra (inflammation of the first metatarsophalangeal joint) being the first joint manifestation in majority of cases. Podagra is not synonymous with gout and is also observed in patients with pseudogout, sarcoidosis, gonococcal arthritis, psoriatic arthritis, and reactive arthritis. The attacks begin abruptly and reach maximum intensity in 8-12 hours. The joints are red, hot, and exquisitely tender (like cellulitis); even a bed sheet on the swollen joint is uncomfortable and frequently wakes up the patient in night. Untreated gout with passage of time becomes polyarticular, which sometimes may be symmetrical. Tophi are collections of uric acid crystals in the soft tissues. They can be found in multiple locations, but the classic location is along the helix of the ear.
Acute flares of gout can occur with use of alcohol, overindulgence of certain foods, trauma, hemorrhage, steroid withdrawal or the use of medications that elevate levels of uric acid like diuretics, pyrazinamide and ethambutol.
‘99er’-Elderly women, particularly women with renal insufficiency and taking a thiazide diuretic, often develop polyarticular arthritis as their first manifestation of gout.
These attacks may occur in coexisting Heberden and Bouchard nodes. Such patients also may develop tophi
more quickly, occasionally without prior episodes of acute gouty arthritis.
Diagnosis
• Synovial fluid examination: It shows crystals that are shaped like needles or toothpicks with pointed ends and are negatively birefringent.
‘99er’-Corticosteroids used to inject joints have a crystalline structure that can be either positively or negatively birefringent. Therefore, interpreting polarized microscopy from a joint that was recently injected with corticosteroids is difficult.
• Serum uric acid: It has no value in diagnosis as it may be normal or low during acute attack.
• X-ray: Soft-tissue swelling or a normal radiograph early in disease. Haziness suggestive of tophi can be seen in late gout, and tophi may calcify. Characteristic punched out erosions with over hanging cortical bone (rat bites) are also seen in advanced stage. Also seen in erosion that is not typical of rheumatoid arthritis (with maintenance of joint space, without periarticular osteopenia).
Treatment
Three steps involved in the management of gout
• Treating the acute attack: NSAIDs are the drugs of choice and Indomethacin is the traditional choice unless the patient is elderly, because of the potential for adverse CNS effects in this age group. Colchicine is the classic medication for gout but is not the preferred medication for the treatment of acute gout. It is most effective during the first 12-24 hours of an attack and its effectiveness declines with the duration of inflammation. Steroids, intra-articular or oral, are given in elderly patients who cannot tolerate NSAIDs or colchicines or when they fail to treat.
• Providing prophylaxis to prevent acute flares: Lowering uric acid with either allopurinol or probenecid can precipitate attacks of gout. When used prophylactically, colchicine can reduce such flares by 85%. The standard dose for prophylaxis is colchicine at 0.6 mg bid. Prophylaxis with colchicine can be started during the acute attack.
• Lowering excess stores of uric acid and to prevent tissue deposition of uric crystals: The goal of therapy is to lower serum uric acid levels to approximately 5-6 mg/
dL. A level > 9 mg/dL denotes higher risk for recurrent gouty arthritis and tophi and patient should undergo this therapy the first time they get a gout attack, else
can wait and start if there is second attack. Probenecid is used in the undersecretors (>80% of adults).
Allopurinol is used in overproducers or patients with renal failure or kidney stones.
‘99er’-Allopurinol and probenecid therapy shouldn’t be started during/ after acute gout attacks.
PSEUDOGOUT
Pseudogout is inflammation caused by calcium pyrophosphate (CPP) crystals and is sometimes referred to as calcium pyrophosphate disease (CPPD). Many cases of pseudogout are idiopathic, but pseudogout has also been associated with aging, trauma, previous joint disease and many different metabolic abnormalities. Most common associations with pseudogout are hyperpara-thyroidism, hypophosphatasia, hypohyperpara-thyroidism, Wilson disease, DM, hypomagnesemia, and hemochromatosis.
It may be clinically indistinguishable from gout but here the most commonly affected joint is knee joint along with others like shoulder, wrist, or ankle. Patient may present with recurrent inflammatory arthritis.
Diagnosis
• Joint fluid examination: It shows typical rectangular, rhomboid, positive birefringent crystals on synovial fluid evaluation.
• X-rays: It may reveal linear radiodense deposits in joint menisci or articular cartilage (chondrocalcinosis).
Treatment Same as gout.
SPONDYLOARTHROPATHIES (SPAS)
They are a family of related disorders that includes ankylosing spondylitis (AS), Reiter syndrome (RS), reactive arthritis (ReA), psoriatic arthritis (PsA), spondyloarthropathy associated with inflammatory bowel disease (IBD), undifferentiated spondy-loarthropathy (USpA), and, possibly, Whipple disease and Behçet disease. Ankylosing spondylitis is the prototypical SpA. First step of diagnosis in all these diseases is X-ray of lumbosacral spine. The SpAs share certain common features like:
• Genetics ( HLA-B27)
• Seronegativity
• Extraarticular manifestations
• Enthesitis (entheses-the location where a bone has an insertion to a tendon or a ligament).
Ankylosing Spondylitis
It is a chronic, painful, degenerative inflammatory arthritis primarily affecting spine and sacroiliac joints, causing eventual fusion of the spine. It is more common in man and starts usually in second to third decade of life.
Clinical Features
Morning stiffness is characteristic, and fatigue is common.
It usually presents with chronic lower back pain in a young man (in his late twenties to early thirties). Morning stiffness lasts at least 1 h and improves with exercise (diagnosis clincher). Stiffness of the spine and kyphosis results in a stooped posture that is characteristic of ankylosing spondylitis at advanced stages. On examination patient shows positive Schober test (measures spine flexion) and sometimes obliteration of the lumbar lordosis. Spine fractures are common with minor trauma.
Extraarticular manifestations are common in AS:
Anterior uveitis, aortic insufficiency that may sometimes lead to congestive heart failure, and third-degree heart block.
Diagnosis
Typical history and examination are very helpful.
X-rays: It is most helpful in diagnosis. The lesions on X-ray progresses from blurring of the subchondral bone plate to irregular erosions of the margins of the sacroiliac joints (pseudowidening) to sclerosis, narrowing, and finally, fusion. Chronic spine inflammation will eventually cause the bamboo spine and squaring of the vertebral bodies.
Treatment
NSAIDs, physical therapy, and exercise are very helpful.
Sulfasalazine is often used in the treatment of ankylosing spondylitis, especially for peripheral joint involvement, for which it has demonstrated efficacy. Treat extra-articular manifestations as dictated by the clinical setting.
Reactive Arthritis
It is a chronic form of arthritis featuring inflamed joints, conjunctivitis, and inflammation of the genital, urinary, or gastrointestinal systems. It’s called reactive immune system that is “reacting” to the presence of bacterial infections in the genital, urinary, or gastrointestinal systems.
Clinical Features
The reaction commonly is seen either against nongonococcal urethritis caused usually by chlamydia, ureaplasma or after an infectious diarrhea caused by Campylobacter (most common), Shigella, or Salmonella organisms.
Reiter syndrome is conjunctivitis and arthritis caused by nongonococcal urethritis along with keratoderma blennorrhagica, circinate balanitis, and oral or genital ulcers.
Diagnosis
X-ray findings will be consistent with a seronegative spondyloarthropathy.
Treatment
It’s is the same as for AS. Methotrexate may be used in severe form of arthritis.
Reiter syndrome may be prevented if urethritis is treated with prompt antibiotic treatment. It also shows improve-ment with 3 weeks tetracycline treatimprove-ment.
‘99er’- Dactylitis (sausage digit) is very uncommon in patients with ankylosing spondylitis. Isolated small-joint involvement of the hands, feet, or dactylitis strongly suggests Reiter syndrome, reactive arthritis, or psoriatic arthritis.
‘99er’- Reiter syndrome in HIV patient- present with a severe form in which the skin manifestation as mentioned above are typically very aggressive. This condition improves on anti-retroviral treatment.
Psoriatic Arthritis- Commonly involves the DIP Enteropathic Arthropathy: associated with UC or CD.