Arthritis Chart
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OSTEOARTHRITIS
Wear and Tear
Osteoarthritis is the degeneration of cartilage (type 2 collagen) in synovial joints. It gradually occurs as we age when cartilage is destroyed faster than it’s made. The disease process is accelerated whenever there is trauma, necrosis or infection to a joint. Without cartilage, the bones grind against each other (eburnation), which hurts like hell and produces characteristic crepitus with range of motion. The pain improves with rest. Weight-bearing joints are particularly vulnerable, since they’re under more physical pressure (obesity is a major risk factor). OA classically arises asymmetrically in our big weight bearing joints (knees, hips, low back), and interestingly, in our distal fingers (DIPs and PIPs). On a cellular level, osteoblasts observe the bony destruction, and they respond by making more bone. The problem is, they end up making bone in places that they shouldn’t, and these little growths are called osteophytes. Osteophytes can pop up in 3 different locations: (a) off to the side (harmful in the spine), (b) into the joint space (limiting ROM) or (c) under the joint space (pushing the joint closer together, sometimes forming a subchondral cyst). The fingers lack a lot of soft tissue, so osteophytes there become very prominent, and that’s why we have names for them. DIP osteophytes are called Heberden nodes, and PIP osteophytes are called Bouchard nodes (B comes before H in the alphabet)
While OA is frequently referred to as a non-inflammatory condition (reasonably so, to differentiate it from RA), some recent literature has identified that this isn’t entirely true. When the articular cartilage is destroyed, the sleepy chondrocytes floating within the cartilage wake up in a panic. They begin producing proteases and cytokines, before they are eventually killed. This cytokine panic accelerates cartilage damage.
All patients benefit from Tylenol and NSAIDs, and some perhaps benefit from joint injections (steroids, etc). While all NSAIDs help, there’s a certain subclass of NSAIDs called the Selective COX-2 Inhibitors (Celecoxib) that are used in OA and RA, as they have less GI side effects than regular NSAIDs (although they might increase clotting).
RHEUMATOID ARTHRITIS
Synovial autoimmunity
Rheumatoid Arthritis is the autoimmune destruction of the synovium inside of joints. Inflammation causes the synovium to swell up with granulation tissue, and this swollen tissue is called a pannus. The inflamed pannus releases cytokines (TNF-a, IL-6) that recruit neutrophils that damage the cartilage. The cytokines also activate osteoclasts that eat away the bone. Since it’s an autoimmune condition, it’s fairly normal to see systemic symptoms like fever, malaise or myalgias, and also, it mainly affects middle aged women. RA is associated with HLA-DR4, but the MOA is not fully known. In RA, the damage takes place when you’re not moving (during sleep), because moving the joints will “wash out” the inflammatory junk. Everyone feels a little stiff when they wake up in the morning, but patients with RA take longer to loosen up (eg, 2 hours). This is called prolonged morning stiffness, and it’s a buzzword for RA. But with enough time, the pain eventually starts to improve with use.
An autoantibody is any antibody made by your body that binds to healthy tissues. Most (if not all) autoimmune diseases involve autoantibodies. One such autoantibody is rheumatoid factor (RF). Despite its name, only 80% of patients with RA have RF. RF is an IgM autoantibody that binds to the inert “stalk,” or Fc portion of IgG antibodies. RF is used as a diagnostic tool and marker of disease activity, which means that you can trend it over time to monitor the effectiveness of your treatment regimen. A more sensitive and specific blood test is citrullinated peptides (citrulline is an amino acid made during inflammation, especially with RA). The damaged synovium tries to heal itself with granulation tissue, but this granulation tissue is problematic. There’s simply no room for it in the joints! And while it works great for skin wounds, it’s not a great tool for healing joints. Granulation tissue is full of fibroblasts and myofibroblasts. The fibroblasts make collagen (which gunks up the joint). The myofibroblasts contract, which (a) pulls the two bones closer together (ankylosis) facilitating eburnation and (b) pulls the entire joint in weird directions, creating joint deformities (especially in the hand).
RA is usually symmetric (I have no idea why). RA likes to attack the peripheral joints (wrists, hands, feet) and neck -- and while the wrist, PIP and MCP joints can be involved, the DIP will be spared. Since the finger joints are already so small and delicate, the pannus can warp the joints into pretty dramatic deformities (like the swan neck deformity).
There are many unusual systemic problems that occur with RA.
Cardiovascular problems like Pericarditis, Aortitis or Small-Vessel Vasculitis.
You can see chronic inflammation diseases like anemia of chronic disease or secondary amyloidosis.
Rheumatoid nodules are lumps that pop up in the skin (and sometimes organs). They feature a central area of necrosis, surrounded by some epithelioid histiocytes.
RA nodules can spread to the lungs, which is called Caplan Syndrome. The nodules are associated with restrictive lung disease, pulmonary fibrosis, pleuritis and pleural effusions.
Felty Syndrome refers to neutropenia and splenomegaly that occurs in some RA patients. If you treat the RA, Felty syndrome will resolve.
Baker’s Cysts are common. These are swollen, painful bursae in the popliteal fossa (behind the knee). They’re mostly asymptomatic, but when they burst they cause symptoms similar to a DVT. Differentiate them with an ultrasound. Note that Baker’s cysts can be found with just about any type of arthritis.
The neck is often affected by RA. Patients should avoid neck manipulation (i.e., OMM, chiropractors, neck thrust during intubation) because that can cause atlantoaxial subluxation, which will shear the spinal cord and vertebral arteries.
The treatment of RA consists of very strong immunosuppressive drugs, collectively referred to as DMARDs or disease-modifying antirheumatic drugs. Unlike NSAIDs, DMARDs have been shown to slow the progression of RA. Methotrexate is the prototypical example of a DMARD. Methotrexate is a folate blocker with numerous side effects including myelosuppression, pneumonitis, hepatotoxicity, aplastic anemia, neurotoxicity, mucositis and teratogenicity. Other classic DMARDs include hydroxychloroquine, sulfasalazine and leflunomide. The recent emergence of biologics has changed the field pretty dramatically. Some examples include anti-JAK antibodies (Baricitinib), anti-TNF antibodies (Infliximab), anti-CD80 antibodies (Abatacept), anti-CD20 antibodies (Rituximab), and anti-IL1 antibodies (Anakinra). Methotrexate is still the first line medication, but I anticipate a lot of change in this field in the near future.
SERONEGATIVE SPONDYLOARTHROPATHIES
Seronegative = No rheumatoid factor = associated with HLA-B27
ANKYLOSING SPONDYLOARTHRITIS (AS) is an autoimmune, cytokine-driven arthritis that causes arthritis and fusion of the spine and sacroiliac joints. The classic patient is an adult male in his 20s or 30s who presents with low back pain and limited spinal ROM. The pain of AS typically improves with exercise, making sleep difficult. The patient’s lumbar x-ray should reveal fusion of the vertebrae, which looks like a bamboo spine. Lumbar x-ray is the recommended screening test for AS. AS is not just limited to the bones. It can also cause uveitis and aortitis. AS is associated with HLA-B27 (there are about 27 Bones in your spine), which is the rare HLA that affects MHC class 1 molecules and causes autoimmune conditions in men more so than women. AS is somehow connected to the gut microbiome, and can involve production of IL-17, TNF-a and prostaglandins. These cytokines can wreak havoc on the spine, sacrum and wherever tendons insert into bone (enthesitis). There’s a lot of new research on AS, so I think it may be higher-yield than you might think!
REACTIVE ARTHRITIS (Reiter Syndrome) is the constellation of autoimmune symptoms that sometimes occurs after getting Chlamydia or a GI infection (less commonly). It can cause urethritis, uveitis and arthritis (Can’t pee, Can’t see, Can’t climb a tree). All of these symptoms are mediated by the immune system, and there is no remaining chlamydia in the body. Note that Reiter was a Nazi doctor, so try and avoid using that eponym if you can.
PSORIATIC ARTHRITIS accompanies 10 to 30% of people with psoriasis (silvery scaly plaques over extensors). It can affect any joint. It especially likes to hit the DIPs, but may also cause diffuse finger swelling, aka dactylitis, aka sausage fingers. They also have a much higher likelihood of having the fingernail problems of psoriasis (nail pitting, onycholysis).
SEPTIC ARTHRITIS
Joint infection
Septic Arthritis is the bacterial infection of a single joint. This is a big deal. “Don’t let the sun set on an infected joint.” The joint will turn big, red, warm and painful -- plus they’ll get a fever. It’s usually due to Staph aureus, but if the patient is young, then consider Gonorrhea (milder symptoms). Septic Arthritis looks like a case of febrile gout. You make the diagnosis with a synovial fluid analysis (sucking the fluid out of the joint with a needle). The fluid will look nasty as hell, kinda like a lemon-flavored milkshake. Treatment begins with antibiotics, but many patients will require a surgical cleanout, and an unlucky few need amputation. Most patients suffer from accelerated arthritis in the affected joint.
Pus aspirated from an infected joint
Synovial Fluid Analysis
GOUT
Crystal joint disease #1
Gout is a crystal arthropathy. Monosodium Urate (MSU) crystals settle into joints and tissues, which hurts very badly. Gout causes pain, redness, swelling and warmth of one joint at a time. It classically affects the base of the big toe. MSU comes from Uric Acid, which itself comes from purine breakdown (A and G). Patients are asymptomatic most of the time. But if their Uric Acid levels spike, the MSU will precipitate into yellow, negatively birefringent, needle-shaped crystals in their joints. The crystals recruit neutrophils, which are responsible for all of the symptoms (which explains why the joint looks very similar to septic arthritis). If you have gout for years and years, you can develop tophi, which are white chalky deposits of MSU that settle in tissues throughout the body (see image below). If the tophi happen to settle into the kidney, it can cause kidney damage. But most tophi settle under the skin, where they feel firm to palpation. Here’s a classic case of gout. A middle aged male eats a steak / wine / ice cream feast for his birthday dinner. He wakes up the next morning with pain, redness and swelling of his big toe.
Acute Treatment
NSAIDs, Steroids and Colchicine - a microtubule inhibitor that impairs neutrophil migration. It swiftly improves inflammation in three seemingly unrelated disorders: Gout, Familial Mediterranean Fever and Pericarditis. Its benefits are limited, because it commonly causes nasty diarrhea and nausea, and it rarely causes agranulocytosis.
Preventative Treatment
Allopurinol - a xanthine oxidase inhibitor that slowly lowers the level of Uric Acid by preventing its formation. It’s the best chronic gout drug, period. But it has a lot of side effects: hepatotoxicity, rashes, and GI distress. Some doctors think that it may worsen an acute flare (by “mobilizing” the crystals, but the science is mixed on that point. Also know that it makes some chemo drugs (6-MP, Azathioprine) more potent, because xanthine oxidase is responsible for breaking them down. Febuxostat - same mechanism as Allopurinol, but some patients who can’t tolerate Allopurinol can tolerate Febuxostat instead. Expensive.
Pegloticase - a Uricase enzyme that turns Uric Acid into the excretable molecule Allantoin. It’s taken from pigs and given as an IV every few weeks.
Probenecid - blocks the reabsorption of Uric Acid in the kidneys, facilitating excretion. It’s a sulfa drug. It also blocks the excretion of Penicillin (original use). By putting uric acid into the urine, it can cause kidney stones.
LESCH-NYHAN SYNDROME is a genetic defect in the HGPRT enzyme, which is a part of the Purine Salvage pathway. Without this salvage path, all of the body’s Guanine has to be turned into Uric Acid (instead of being transformed into Adenosine or IMP or something). Although rare, it’s a high-yield disorder. It characteristically causes patients to suffer from severe intellectual disability and self-mutilation (biting off their own lips, for example), in addition to gouty arthritis.
PSEUDOGOUT
Crystal joint disease #2
Pseudogout has similar symptoms of gout, but is due to the deposition of a different crystal, Calcium Pyrophosphate (CPP) instead of MSU. Pseudogout is also called calcium pyrophosphate dihydrate crystal deposition disease (CPPD). CPP creates blue, positively birefringent, rhomboid-shaped crystals under polarized light. While gout usually affects the big toe, pseudogout more commonly affects the knee. There is a classic x-ray finding with pseudogout -- chondrocalcinosis -- which refers to the buildup of wisps of calcium inside the joint space. You should recognize images of it.
Gout: Yellow Needles
Pseudogout: Blue Rhomboids
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