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Seronegative and septic arthritis: Pathology review



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Musculoskeletal system pathology review

Seronegative and septic arthritis: Pathology review


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USMLE® Step 1 style questions USMLE

10 questions

A 75-year-old woman presents to the emergency department for evaluation of right knee pain for the past two days. Medical history is notable for hypertension, type II diabetes mellitus, and knee osteoarthritis status post-bilateral total knee arthroplasty. Temperature is 38.5 °C (101.3 °F), blood pressure is 142/89 mmHg, pulse is 115/min, respirations are 20/min and SpO2 is 99% of room air. On physical examination, the right knee appears swollen and is tender to palpation. An arthrocentesis is performed and cultures reveal a Gram-positive coccus which is catalase-positive and coagulase-negative. Which of the following organisms was most likely identified?  

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Yifan Xiao, MD

Maurice is a 28 year old male who presents with a 2 year history of gradually progressive low back pain and stiffness. He mentions that the pain wakes him up several times at night, and that the stiffness tends to be worse when he wakes up and improves as he moves. Examination shows mild deformity of the spine and hip, as well as tenderness over the buttock. Then you see Clint, a 63 year old male shows up with a red, warm and swollen left knee, which hurts so much he can barely walk. Clint tells you that symptoms started a few days ago, after he tripped and cut his knee. His body temperature is 38 celsius degrees or 100.4 degrees Fahrenheit. X-rays are ordered in both cases, showing, in Maurice’s case, erosion of the sacroiliac joint. On the other hand, in Clint’s case, X-rays look pretty normal, so an arthrocentesis is performed, revealing that synovial fluid is purulent.

Based on the initial presentation, both cases seem to have some form of arthritis. But first, a bit of physiology real quick. There are many types of joints, including fibrous, cartilaginous, and synovial joints. synovial joints, like those of the wrist, elbow, knees, shoulders, and hips, are mobile joints that connect two bones via a fibrous capsule that is continuous with the periosteum, which is the outer layer of bones. The fibrous capsule is lined with a synovial membrane, which has cells that remove debris and produce synovial fluid. This is a viscous fluid found inside the joint capsule which lubricates joint. Together, the synovial membrane and articular cartilage form the inner lining of the joint space.

Now, arthritis refers to a group of diseases that cause destruction of one or more joints. First, we have seronegative arthritis, which is called seronegative because there’s an absence of both rheumatoid factor or RF, and anti-cyclic citrullinated peptide antibody or anti-CCP, which are commonly found in rheumatoid arthritis. Something specific to note is that seronegative spondyloarthropathies have a strong association with the gene HLA-B27, which encodes for a specific type of MHC class I molecule.

Now there are several subtypes of seronegative spondyloarthropathies and you can remember them by a mnemonic PAIR, where P stands for Psoriatic arthritis; A for Ankylosing spondylitis; I for Inflammatory bowel disease-associated arthritis; and R for Reactive arthritis.

Let’s start with psoriatic arthritis, which occurs in some individuals with psoriasis or with a family history of psoriasis. It is an autoimmune disease characterized by joint inflammation. Exactly what causes the immune system to go haywire and attack the joints is unclear. Although the HLA-B27 gene is linked to the disease, it’s not enough to trigger psoriatic arthritis on its own, and environmental factors like physical trauma or an infection seem to play a role as well. Now, it all starts with psoriasis, which is an autoimmune condition where skin self antigens are seen as foreign. When that happens, T cells start releasing cytokines that recruit and activate other immune cells to release TNF, IL-12, and IL-23. This triggers keratinocytes and fibroblasts to proliferate, which leads to the formation of psoriatic plaques. These are red, raised patches with silvery scales made up of dead skin cells. In some individuals with psoriasis, T cells also go to the joints and trigger the activation of osteoblasts and osteoclasts, leading to joint erosion and ossification, which can ultimately cause arthritis and severe deformities. Now, arthritis usually occurs after the psoriatic plaques have appeared, but it can sometimes precede them, which makes diagnosis that much harder. For your exam, it’s important to note that less than 30% of individuals with psoriasis develop psoriatic arthritis.

Symptoms of psoriatic arthritis typically include pain, swelling, and stiffness of the affected joints. There are several types of psoriatic arthritis, depending on which joint is affected. The most common one is the distal interphalangeal predominant type, which generally affects the joints nearest to the ends of the fingers and toes, leading to dactylitis, which is the inflammation of the fingers, also known as sausage fingers and nail abnormalities like ridging or pitting. Over time, some individuals with distal interphalangeal predominant type can also develop severe bone erosions and finger deformities. In severe cases, this can evolve into another type of psoriatic arthritis, which is arthritis mutilans. In arthritis mutilans, extensive bone erosion at the fingers creates a telescopic digit appearance that results in a person having what’s called the opera-glass hand.

Diagnosis of psoriatic arthritis involves an X-ray, which may show joint erosion and osteopenia. The most characteristic feature though is the pencil-in-cup radiographic sign, which arises from the periarticular erosions and resorption of the bone, making it look slimmer than the soft tissue around it, sort of like a pencil in a cup.

Treatment of mild cases of psoriatic arthritis includes NSAIDs. In more severe cases, non-biologic DMARDs can be helpful, especially leflunomide. If both NSAIDs and non-biologic DMARDs fail, biologic DMARDs like TNF–inhibitors can be used to stop the disease from progressing. Rarely, surgery is done to repair the damaged joints.

Next, ankylosing spondylitis is a chronic spondyloarthropathy that most often affects young and middle aged males, but its exact cause is unknown. One theory suggests an underlying autoimmune reaction, where T cells mistake type I and type II collagen in the joints as foreign.

Now, ankylosing spondylitis typically affects the spine, making it really stiff. Characteristically, there’s inflammation of the intervertebral joints, as well as the facet joints. Remember that there are two types of joints between the vertebrae: the intervertebral joint, consisting of two vertebral bodies between which lays an intervertebral disc, which is made of type I and II collagen, and has an outer fibrous ring, called the annulus fibrosus, and an inner jelly-like substance, known as nucleus pulposus. And then each vertebra also has four facet joints, one pair with the vertebra above and one with the vertebra below. Sometimes, ankylosing spondylitis can also affect the sacroiliac joints, between the sacrum and the hip bones, or the joints of the cervical and thoracic region. In any case, there’s destruction of the articular cartilage, so fibroblasts are activated and they start to replace the destroyed joint with fibrin. Fibrin then deposits in layers to form a tough fibrous band around the joints, limiting their range of motion. Eventually osteoblasts get activated too, triggering a process called ossification. That’s when the fibrous tissue at the joint edges within the annulus fibrosus turns into small bony outgrowths called syndesmophytes.

Ankylosing spondylitis causes articular symptoms, such as morning stiffness and lower back pain, which is worse at night, lasts for more than 30 minutes, and improves with movement and exercise. Individuals may also have kyphotic deformity where there’s an excessive outward curvature of the thoracic spine, as well as limited range of motion in the spine caused by both fibrin deposition and by syndesmophytes. Things can get so bad that the affected part of the spine becomes completely immobile. If ankylosing spondylitis affects the sacroiliac joints, it typically causes lower back or buttock pain and tenderness upon palpation, and if it affects the cervical or thoracic region it can cause neck or chest wall pain and stiffness.

Ankylosing spondylitis can also present extra-articular symptoms like weight loss, fever, and fatigue. Other high-yield symptoms include uveitis and tendonitis, and, because the ribs and vertebrae are involved in breathing, spine stiffness can cause shortness of breath due to impaired chest expansion. Another way ankylosing spondylitis can affect breathing is by causing restrictive lung disease, and specifically pulmonary fibrosis in the apical parts of the lungs. In the heart, it can cause aortitis, or aortic wall inflammation, leading to dilation of the aortic ring and aortic insufficiency.

Diagnosis is usually based on an X-ray, CT scan, or MRI, which can detect erosion and narrowing of the joint spaces. Another characteristic finding is the bamboo spine, which is caused by the ossification of the annulus fibrosus on the outside of a straightened spine, giving it a hollow appearance. Finally, genetic testing for HLA-B27 can be done to confirm the diagnosis.

Inflammation and pain from ankylosing spondylitis are usually treated with NSAIDs like ibuprofen. Pain and mobility issues can also be relieved by exercise or physical therapy. Remember that these individuals also need frequent monitoring of their chest expansion. In more severe cases, DMARDs like sulfasalazine and methotrexate can be taken to control symptoms and slow progression.


Seronegative and septic arthritis are two different forms of arthritis, each with its causes and symptoms. Seronegative arthritis refers to a type of arthritis in which a person tests negative for rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies, which are markers commonly associated with rheumatoid arthritis. Seronegative arthritis can be caused by a variety of conditions, including psoriatic arthritis, ankylosing spondylitis, reactive arthritis, etc.

Septic arthritis, on the other hand, is a severe form of arthritis, often caused by bacterial infections. The infection can enter the joint through a break in the skin, or from an infection in another part of the body that spreads through the bloodstream. Septic arthritis is a medical emergency and requires prompt treatment with antibiotics to prevent joint damage and systemic spread of the infection.

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