›

Gout, Psoriatic Arthritis, & Other Arthritides

Notes

Gout, Psoriatic Arthritis, & Other Arthritides

Sections




Non-autoimmune arthritides

See Osteoarthritis & Rheumatoid Arthritis for a review of the most common non-autoimmune arthritis (osteoarthritis).

Gout

Crystal arthritis

  • Begin with crystal arthritis, which we divide into gout and pseudogout (now known as calcium pyrophosphate deposition disease (CPPD)).

See: Gout

Hyperuricemia

  • Indicate that gout stems from hyperuricemia and resultant deposition of monosodium urate crystals in the joints, which activate a painful inflammatory cascade.
  • Note that > 90% of the time the hyperuricemia in gout most often stems from underexcretion rather than overproduction of urate and that acute attacks are often triggered by alcohol (3-4 beers/day), certain foods (excess purines), certain medications (which we address below), radiation therapy, trauma, exercise, as well as certain underlying medical conditions.

Needle-shaped, negative birefringence

  • Indicate that polarized light microscopy reveals urate crystals that are needle-shaped and have negative birefringence.
  • Draw a slide and show two needle-shaped crystals: a yellow horizontally-oriented crystal (its color indicates that it is in parallel to the slow wave of the light (the axis of slow vibration)) and a blue vertically-oriented crystal (in perpendicular to the axis of the slow vibration).
    • Negative birefringence refers to the physics of optical light refraction that occurs when polarized light is shown through a crystal.
    • If the refractive index of the light in parallel to the long axis of the crystal is greater than that in perpendicular, then there is negative birefringence; whereas, if the opposite is true (if the index in parallel is less than the index in perpendicular), then there is positive birefringence.

Acute Attack: Podagra

  • Patients are typically asymptomatic with hyperuricemia for 20 years or so before they then have their first acute painful inflammatory attack.
  • Indicate that this most commonly occurs (in ~ half of cases) at the first metatarsophalangeal (MTP joint), called podagra.

Chronic disease: Tophi

  • Show that with chronic gout, tophi can form within synovial tissues and extrasynovial tissues (ie, the skin).
  • Draw a standard H&E slide and show a tophus – a deposit of monosodium urate crystals – surrounded by inflammatory cells.

Disease Course

  • Gouty attacks are self-limited – they last for ~ 10 days and resolve (as the proinflammatory attack converts to an anti-inflammatory response) but then subsequently return months to years later. Over time, the attacks occur with greater frequency and duration, less acuity, and with more joint involvement.

Treatment

  • Acute treatment involves the use of NSAIDs (eg, indomethacin), as well as glucocorticoids, and colchicine.
  • Chronic treatment involves mitigating risk factors for gouty flares and the use of urate-lowering therapies, namely xanthine oxidase inhibitors (allopurinol, mostly, as febuxostat), and other urate-lowering therapies (eg, probenecid).

Iatrogenic causes of gout attacks

  • We can use the acronym CAN'T LEAP to remember drugs that induce gout through decrease of urate excretion:
    • Cyclosporine
    • Alcohol
    • Nicotinic acid
    • Thiazide diuretics
    • Loop diuretics (Lasix)
    • Ethambutol
    • Aspirin (at low dose)
    • Pyrazinamide

calcium pyrophosphate deposition disease (pseudogout)

Calcium pyrophosphate deposition

  • Now, let's address calcium pyrophosphate deposition disease (formerly but still widely called pseudogout), which as its name suggests involves calcium pyrophosphate deposition.

See: Pseudogout

Demographic

  • The disease is quite different than gout (which is why pseudogout is really a misnomer) – it tends to occur in older individuals (older than 50 yo and most commonly over 80 yo (note that gout tends to occur in the 40s or 50s in men and later on in women).

Rhomboid-shaped, positive birefringence

  • Show that polarized light microscopy reveals rhomboid-shaped crystals with positive birefringence – they are blue in parallel to the slow wave of light (unlike gout crystals, which are needle-shaped and have negative birefringence).

Pathogenesis

  • Show that the disease involves cartilaginous or synovial release of calcium pyrophosphate crystals into the joint space, most commonly the knee (whereas in gout it's most often the MTP joint).
    • This deposition produces an inflammatory cascade. There is cartilaginous calcification on X-Ray (chondrocalcinosis).

Treatment

  • Similar to gout, we use NSAIDs (eg, indomethacin), as well as intra-articular glucocorticoid injections or oral prednisone to reduce inflammation. Typically, the response is less dramatic than in gout and, therefore, requires a longer duration of therapy.

"Blue P's"

  • We can use the mnemonic the Blue P's to help us remember some highlights of the disease:
    • Pseudogout has calcium Pyrophosphate deposition that exhibit Positive birefringence – they are blue when in parallel to the slow wave of polarized light.

References

Gout
Pseudogout

infectious (septic) arthritis

  • Next, let's briefly address infectious (septic) arthritis; we address these microorganisms, themselves, in detail in our microbiology section.
  • We will focus on the distinction of nongonococcal and gonococcal forms of septic arthritis.

Nongonococcal

  • Nongonococcal causes typically arise in the immune-compromised (thus in small children and the elderly), present as a monoarthritis (the knee, hip and other large weight-bearing joints have the highest propensity for septic arthritis) without extra-articular disease (meaning without tenosynovitis or dermatitis).
  • Joint cultures are almost always positive, blood cultures are positive about half of the time, and the outcome is mixed and can require antibiotics in conjunction with joint decompression and evacuation.
  • It most commonly manifests as a warm, painful joint that is infected by hematogenous spread. Note that the presentation is typically delayed if a joint prosthesis is present or, less commonly, arthrocentesis.
  • Staphylococcus aureus and streptococcus pyogenes are the most common cause of nongonococcal septic arthritis and osteomyelitis in adults.
    • S. aureus is an especially common cause because it contains microbial surface components recognizing adhesive matrix molecules (MSCRAMMS) in the cell wall peptidoglycan.

Gonococcal

  • Gonococcal arthritis (caused by Neisseria gonorrhoeae), instead, typically presents in young individuals as a migratory (polyarthritis) with associated tenosynovitis and dermatitis.
  • Joint cultures are positive in a minority of cases, blood cultures are rarely positive, and antibiotics are highly effective (previously penicillin and quinolones but now ceftriaxone followed by either doxycycline or cefixime).

Autoimmune Arthritides

Next, let's address autoimmune forms of arthritis (other than rheumatoid arthritis). Historically, these forms of arthritis were referred to as seronegative spondyloarthropathies but this terminology has fallen out of favor. See Osteoarthritis & Rheumatoid Arthritis for a review of the most common autoimmune arthritis (rheumatoid arthritis)

HLA-B-27 & Inflammatory Bowel Disease

First, a couple of generalities:

  • There are varying degrees of association between HLA-B27 and these disorders -- far and away, however, the strongest association is between HLA-B27 and ankylosing spondylitis.
  • Also, note that this group of disorders can be associated with inflammatory bowel disease (Crohn's disease and ulcerative colitis).

ankylosing spondylitis

See: ankylosing spondylitis

Ankylosis (fusion)

  • First, let's address ankylosing spondylitis (the major form of axial spondyloarthritis). It's helpful to remind ourselves that ankylosis means fusion – we drew ankylosis in the pathology of rheumatoid arthritis.

Costovertebral joint fusion

  • The most illustrative example of ankylosis (joint fusion) in ankylosing spondylitis is costovertebral joint fusion and other variants of chest wall ankylosis, which can result in reduced chest wall expansion and cause ventilatory impairment through chest wall restriction.

Sacroiliitis

  • The key sites of fusion in ankylosing spondylitis are the sacroiliac joint, called sacroiliitis, and the lumbar spine.
  • For sacroiliitis, draw a pelvis – show the sacrum and ileum and indicate symmetric inflammation at the bilateral sacroiliac joints. This erosive process creates a "pseudo-widening" and ultimately an ankylosis of the joint. Sacroiliitis presents with SI joint tenderness.

Lumbar spine disease (Bamboo spine)

  • For the lumbar spine, first draw a healthy spine with well-shaped vertebrae and good intervertebral spaces and discs.
  • Then, draw a spine with ankylosing spondylitis. Show that the vertebrae are squared (there edges are straightened) and there is reduction in height of the intervertebral spaces, which occurs via syndesmophyte bridges between the vertebrae (intervertebral bony bridges), creating a "bamboo" appearance.
    • These lumbar changes manifest with profound pain and stiffness in the morning, which improves with exercises, and then worsens in the evening.
    • Note that the Schober test is used to assess the degree of forward flexion of the lumbar spine.

Enthesitis

  • Another important musculoskeletal manifestation is enthesitis (which we also address in psoriatic arthritis) – it's inflammation at the insertion of a tendon (such as the achilles), ligament, or joint capsule into the bone. The inflammation can lead to fibrosis (new bone formation).

HLA-B27 & Male sex

  • Next, indicate that ankylosing spondylitis has a strong association with HLA-B27 and male sex. Roughly 90% of white individuals with the AS are HLA-B27 positive (it is less common in non-white patients).

Extraskeletal manifestations

  • Uveitis, which can occur in up to one-third of patients.
  • Aortic insufficiency and other cardiac manifestations.
  • Additional spine complications, including discitis, cauda equina syndrome, and atlantoaxial subluxation.
  • Pulmonary fibrosis along with the previously mentioned chest wall restriction.
  • Kidney manifestations.

psoriatic arthritis

Pencil-in-cup deformity

  • First, let's draw the classic pencil-in-cup deformity. Draw a normal skeletal structure of a finger. Then show the pencil-in-cup sign, which occurs through periarticular erosion and bone resorption.
    • This finding occurs in many different arthropathies but is especially common in the DIP joint in psoriatic arthritis

Dactylitis

  • Next, let's address dactylitis (sausage digit) in psoriatic arthritis. Draw a foot and show dactylitis of the 3rd and 4th digits – show inflammation and swelling of these toes: the most common site of dactylitis in psoriatic arthritis.

Nail dystrophy

  • Now, psoriatic nail dystrophy – include toenails and show dystrophic features, which include: onycholysis (nail detachment), vertical ridges, pitting, and hyperkeratosis.

Additional Features

  • Plaque psoriasis – psoriatic arthritis is a manifestation of the skin disease psoriasis: it affects up to one-third of patients with psoriasis and tends to develop several years after the onset of skin lesions.
  • Axial spondyloarthritis – it's a less prominent feature of psoriatic arthritis than ankylosing spondylitis but still an important one.
  • Enthesitis, which refers to tendon/ligament inflammation (especially of the achilles).

Genetic predisposition

  • Note that psoriatic arthritis is considered a polygenic disorder with numerous HLA associations, including: HLA-Cw6, HLA-B38, HLA-B39, in addition to HLA-B27.

Reactive arthritis

Sterile, inflammatory arthritis

  • Reactive arthritis is a sterile, inflammatory arthritis that occurs 1 to 4 weeks post a nongonococcal gastrointestinal or genitourinary infection, typically in young adults 20 to 40 years old. It's typically self-limited but can last months and or be recurrent and chronic and require long-term immunosuppression.
    • Please note that the term "Reiter's syndrome" is not longer used due to its relation to the individual it was named after. See the following article for details: Reiter's syndrome

Classic Triad

  • Include the following classic clinical triad: conjunctivitis (can't see), urethritis (can't pee), arthritis (can't bend the knee). Although the triad is classic, these three features only occur together in roughly one-third of patients.

HLA-B27

  • HLA-B27 confers increased risk of getting the disease.

Infectious Cause

  • About half of the time and infectious triggers is unable to be identified, when it is, the most common infectious cause of reactive arthritis are as follows:
    • Gastrointestinal: Salmonella, Shigella, Yersinia, Campylobacter
    • Urogenital: Chlamydia

adult-onset Still's disease

  • Now, let's address adult-onset Still's disease, which we distinguish from the spondyloarthropathies.
  • Indicate that it manifests with severe arthritis; daily, spiking fever (this is called a quotidian (once daily) or double quotidian (twice daily) fever); and an often unnoticed, salmon-colored, transient, nonpruritic rash.
  • Patients are typically very ill only when they are febrile (they feel well when they are afebrile), so it's easy to mistake the patient for appearing well when they are euthermic.

juvenile idiopathic arthritis

  • Lastly, let's include juvenile idiopathic arthritis (formerly juvenile rheumatoid arthritis).
  • Indicate that this refers to a chronic inflammatory arthritis lasting longer than 6 weeks in a child that is younger than 16 years old.
  • Indicate that it represents a heterogenous group of disorders, including: oligoarthritis, polyarthritis: rheumatoid factor (RF) positive or negative, systemic arthritis, psoriatic arthritis, and enthesitis-related arthritis.

Board Review

Getting ready for boards? Review these concise, bulleted high yield summary of the following topics: gout, pseudogout, ankylosing spondylitis, psoriatic arthritis, and septic arthritis with brief comparisons for effective memory consolidation.

USMLE & COMLEX-USA

Nurse Practitioner (NP)

Physician Assistant (PA)

Internal Medicine (ABIM)

References

  • Aggarwal, Rohit, Katherine Liao, Raj Nair, Sarah Ringold, and Karen H. Costenbader. "Anti-Citrullinated Peptide Antibody (ACPA) Assays and Their Role in the Diagnosis of Rheumatoid Arthritis." Arthritis and Rheumatism 61, no. 11 (November 15, 2009): 1472–83. https://doi.org/10.1002/art.24827.
  • Choy, Ernest. "Understanding the Dynamics: Pathways Involved in the Pathogenesis of Rheumatoid Arthritis." Rheumatology (Oxford, England) 51 Suppl 5 (July 2012): v3-11. https://doi.org/10.1093/rheumatology/kes113.
  • Efthimiou, Petros. Absolute Rheumatology Review. Springer Nature, 2019.
  • Imboden, John B., David B. Hellmann, and John A. Stone. Current Diagnosis & Treatment in Rheumatology, Fourth Edition. McGraw Hill Professional, 2020.
  • Judkins, Shelley W, and P Joanne Cornbleet. "Synovial Fluid Crystal Analysis," 2018, 6.
  • Kanaan, Sami B., Oyku Sensoy, Zhen Yan, Vijayakrishna K. Gadi, Michael L. Richardson, and J. Lee Nelson. "Immunogenicity of a Rheumatoid Arthritis Protective Sequence When Acquired through Microchimerism." Proceedings of the National Academy of Sciences 116, no. 39 (September 24, 2019): 19600–608. https://doi.org/10.1073/pnas.1904779116.
  • McInnes, Iain B., and Georg Schett. "The Pathogenesis of Rheumatoid Arthritis." Review-article. http://dx.doi.org.proxy.medlib.uits.iu.edu/10.1056/NEJMra1004965. Massachusetts Medical Society, December 7, 2011. World. https://doi.org/10.1056/NEJMra1004965.
  • Queiro, Rubén, Isla Morante, Iván Cabezas, and Belén Acasuso. "HLA-B27 and Psoriatic Disease: A Modern View of an Old Relationship." Rheumatology 55, no. 2 (February 1, 2016): 221–29. https://doi.org/10.1093/rheumatology/kev296.
  • Sophia Fox, Alice J., Asheesh Bedi, and Scott A. Rodeo. "The Basic Science of Articular Cartilage." Sports Health 1, no. 6 (November 2009): 461–68. https://doi.org/10.1177/1941738109350438.
  • West, Sterling. Rheumatology Secrets E-Book. Elsevier Health Sciences, 2014.