Septic Arthritis

Infectious (Septic) Arthritis: Risk Factors, Symptoms & Diagnosis

Septic Arthritis | Johns Hopkins Medicine

Infectious arthritis is an infection in a joint. It may also be referred to as septic arthritis. It occurs when an infection caused by a bacteria or virus spreads to a joint or the fluid surrounding the joint.

This fluid is called the synovial fluid. This infection usually begins in another area of the body and spreads through the bloodstream to the joint tissue.

The infection may also enter the body through surgery, open wounds, or injections.

Infectious arthritis usually only occurs in one joint. The condition typically affects a large joint such as the knee, hip, or shoulder. It occurs more often in children, older adults, and people who use illegal drugs.

The symptoms of infectious arthritis can vary depending on your age and the medications you’re taking. The symptoms may include:

  • severe pain that worsens with movement
  • swelling of the joint
  • warmth and redness around the joint
  • a fever
  • chills
  • fatigue
  • weakness
  • decreased appetite
  • a rapid heart rate
  • irritability

Certain people are more ly to get infectious arthritis than others. The risk factors include:

  • having joint problems such as arthritis, gout, or lupus
  • having a history of joint surgery
  • having certain skin conditions
  • having open wounds
  • abusing illegal drugs or alcohol
  • taking drugs that suppress the immune system
  • having a weakened immune system
  • having cancer
  • smoking
  • having diabetes

Your doctor will examine your joint and ask you questions about your symptoms. If they suspect you have infectious arthritis, they may order additional tests.

An arthrocentesis is a test frequently used to diagnose this condition. It involves inserting a needle into the affected joint to take a sample of synovial fluid.

The sample is sent to the lab to be examined for color, consistency, and the presence of white blood cells and bacteria.

The information from this test can tell your doctor if you have an infection in the joint and what is causing the infection.

Your doctor may also take a blood sample from you. This is another way to check your white blood cell count and to determine if any bacteria are present in your bloodstream. This information can help your doctor determine the severity of the infection.

Imaging tests may also be ordered to confirm the presence of infection. These tests can also help your doctor see if your joint has been damaged by the infection. Imaging tests used for infectious arthritis include:

  • X-rays
  • MRI scans
  • CT scans
  • nuclear scans

Treatment for infectious arthritis caused by a bacteria usually begins with antibiotics to kill the bacteria causing the infection. Your doctor will use the information from your tests to choose an antibiotic that’s effective for the type of bacteria present in your joint.

The infection needs to be treated promptly and aggressively to prevent osteoarthritis and damage to your joint. As a result, your doctor may order intravenous antibiotics, which are given through your veins. This treats the infection more quickly than oral antibiotics.

Most people begin to feel better within 48 hours of their first antibiotic treatment.

Your doctor may also prescribe oral antibiotics to treat the infection. Oral antibiotics for infectious arthritis usually need to be taken for six to eight weeks. It’s important to take the entire course of antibiotics to treat the infection effectively.

Your doctor will prescribe antifungal medication instead of antibiotics if a fungus is causing your infection.

Infectious arthritis caused by a virus doesn’t require medication.

Synovial Fluid Drainage

Many people with infectious arthritis need to have their synovial fluid drained. This is done to remove the infected fluid, ease pain and swelling, and prevent further damage to the joint. Synovial fluid is often drained using arthroscopy, but it can be done in an open surgical procedure.

With arthroscopy, your doctor will make several small incisions near the affected joint. Then, they’ll insert a small tube containing a camera into the incision.

Your doctor will use the camera image to guide them in suctioning the infected fluid from your joint. Usually, a drain or tube will be inserted and left in the joint to keep the joint from swelling again.

This drain is then removed in a few days.

Sometimes, a doctor can use a small needle to remove infected fluid without requiring surgery. This is called arthrocentesis. This procedure often has to be repeated over the course of several days to ensure the fluid has been removed.

Other Treatment Options

Most cases of infectious arthritis require surgery, such as arthroscopy or an open procedure, to wash out the joint. On occasion, surgery is required to remove any damaged sections of the joint or replace the joint, but this is only done after the infection has been treated.

Other treatment methods to reduce pain may be used along with treatment for the infection. These methods include:

  • using nonsteroidal anti-inflammatory drugs
  • resting the joint
  • splinting the affected joint
  • going to physical therapy

Infectious arthritis is a very treatable condition if it’s treated early and aggressively. You’ll most ly see an improvement in your symptoms within 48 hours of starting treatment. Untreated infectious arthritis can cause permanent joint damage. See your doctor if you have joint pain or swelling.


Septic Arthritis

Septic Arthritis | Johns Hopkins Medicine

Linkedin Pinterest Arthritis

Septic arthritis is an infection in the joint (synovial) fluid and joint tissues. It occurs more often in children than in adults. The infection usually reaches the joints through the bloodstream. In some cases, joints may become infected due to an injection, surgery, or injury.

What causes septic arthritis?

Different types of bacteria, viruses, and fungi can infect a joint. The types that can cause septic arthritis include:

  • Staphylococci. These are common bacteria that often cause skin infections.
  • Haemophilus influenzae.These are bacteria that can infect the larynx, trachea, and bronchi.
  • Gram negative bacilli. This is a group of bacteria that includes E. coli.
  • Streptococci. This is a group of bacteria that can lead to a wide variety of diseases.
  • Gonococci. This is the bacterium that causes gonorrhea.
  • Viruses. Viruses such as HIV can infect the joints of people of all ages.

The most common type of bacteria that causes septic arthritis is called Staphylococcus aureus. It is also known as S. aureus. The bacteria can enter the body in a number of ways, such as:

  • A broken bone that goes through the skin (open fracture)
  • An infection that spreads from another place on the body, such as the skin or genitals
  • An infected wound
  • Foreign object that goes through the skin
  • Injury that breaks the skin

Who is at risk for septic arthritis?

Risk factors for septic arthritis include:

  • A systemic blood-borne infection
  • IV drug use
  • Osteoarthritis
  • Past history of septic arthritis
  • Rheumatoid arthritis

Other factors that may increase the risk for septic arthritis include:

  • Alcoholism
  • Diabetes
  • HIV
  • Lung or liver disorders
  • Old age
  • Suppressed immune system

What are the symptoms of septic arthritis?

The most common joints affected by septic arthritis are the knee, hip, shoulder, elbow, wrist, and finger. Most often, only one joint is affected. Symptoms can occur a bit differently in each person, but common symptoms include:

  • Fever
  • Joint pain
  • Joint swelling

The symptoms of septic arthritis can look other health conditions. Make sure you see your healthcare provider for a diagnosis.

How is septic arthritis diagnosed?

Early diagnosis of septic arthritis is important. This is to prevent permanent damage to the joint. The process starts with a medical history and a physical exam. Tests may also be done, such as:

  • Removal of joint fluid. This is done to check for white blood cells and bacteria.
  • Blood tests. These are done to look for bacteria.
  • Phlegm, spinal fluid, and urine tests. These are done to look for bacteria and find the source of infection.

How is septic arthritis treated?

Treatment will depend on your symptoms, age, and general health. It will also depend on how severe the condition is.

Septic arthritis often needs treatment right away with antibiotics. This can improve symptoms within 48 hours. Some infections caused by fungi need treatment with antifungal medicine. Viral infections are not treated with medicine.

A fluid called pus may be drained from the joint. A buildup of pus can damage the joint. The pus is drained with a needle, tube, or surgery.  It is possible that pus may need to be drained multiple times from the joint over the course of treatment. Other treatment may include:

  • Medicines for pain and fever
  • Physical therapy to keep muscle strength
  • A splint on the joint to relieve pain

What are the complications of septic arthritis?

Septic arthritis can destroy the joint cartilage. This can cause permanent damage to the joint.

When should I call my healthcareprovider?

If your symptoms get worse or you have new symptoms, let your healthcare provider know.

Key points about septic arthritis

  • Septic arthritis is an infection in the joint (synovial) fluid and joint tissues.
  • Different types of bacteria, viruses, and fungi can infect a joint.
  • Symptoms include fever, joint pain, swelling, redness, and warmth.
  • Quick treatment with antibiotics is needed to halt the risk of joint damage.
  • Other treatments include medicines for pain and fever, drainage of the joint, physical therapy, and a splint.

Next steps

Tips to help you get the most from a visit to your healthcare provider:

  • Know the reason for your visit and what you want to happen.
  • Before your visit, write down questions you want answered.
  • Bring someone with you to help you ask questions and remember what your provider tells you.
  • At the visit, write down the name of a new diagnosis, and any new medicines, treatments, or tests. Also write down any new instructions your provider gives you.
  • Know why a new medicine or treatment is prescribed, and how it will help you. Also know what the side effects are.
  • Ask if your condition can be treated in other ways.
  • Know why a test or procedure is recommended and what the results could mean.
  • Know what to expect if you do not take the medicine or have the test or procedure.
  • If you have a follow-up appointment, write down the date, time, and purpose for that visit.
  • Know how you can contact your healthcare provider if you have questions.


Johns Hopkins Vasculitis Center

Septic Arthritis | Johns Hopkins Medicine

Rheumatoid Vasculitis (RV) is an unusual complication of longstanding, severe rheumatoid arthritis. The active vasculitis associated with rheumatoid disease occurs in about 1% of this patient population.

RV is a manifestation of “extra-articular” (beyond the joint)rheumatoid arthritis and involves the small and medium-sized arteries in the body. In many of its disease features, RV resembles polyarteritis nodosa.

Other common extra-articular manifestations of rheumatoid arthritis, such as inflammation in the sac surrounding the heart (pericarditis), inflammation in the lining of the lungs (pleuritis), and interstitial lung disease (resulting in fibrosis or scarring of the lungs).

Who gets Rheumatoid Vasculitis? A typical patient

RV can affect a person from any ethnic background, either gender, and from any age group. However, more often than not, the typical patient has long-standing rheumatoid arthritis with severe joint deformities from the underlying arthritis. Although the arthritis has usually led to significant joint damage, at the onset of RV the joint disease is paradoxically quiet.

Figure: Patient with joint damage from rheumatoid arthritis. Note the bulbous swelling of some knuckles and lateral (ulnar) deviation of the fingers.

Classic symptoms of Rheumatoid Vasculitis

RV has many potential signs and symptoms.

The manifestations of RV can involve many of the body’s different organ systems, including but not limited to the skin, peripheral nervous system (nerves to the hands and feet) , arteries of the fingers and toes causing digital ischemia, and eyes with scleritis. Scleritis (inflammation of the white part of the eye) commonly occurs in the setting of RV. This ocular complication requires urgent treatment with immunosuppressive medications.

Figure: Digital ischemia – this image shows a blood flow deficiency in the tip of the finger caused by an obstruction of the digital artery.

Figure: Scleritis – Inflammation of the sclera (the white of the eye) causing redness, light sensitivity and pain.

In addition, generalized symptoms such as fever and weight loss are common.

As is true with other forms of vasculitis that involve the skin, cutaneous lesions can erupt on various areas of the body in RV, with a predilection for the lower extremities. Typical findings include ulcers concentrated near the ankles.

Figure: Cutaneous ulcer – an open skin sore caused by an obstruction of the small blood vessels in the superficial ulcers or obstruction of medium vessels in a deeper ulcer.

Small nail fold infarcts (small spots around fingernail) can

occur in rheumatoid arthritis

but these do not necessarily signify the presence of systemic vasculitis and do not necessitate a change in rheumatoid arthritis treatment.

Nerve damage can cause foot or wrist drop, known in medical terminology as “mononeuritis multiplex”. The images below show a patient with a right wrist drop and a patient with right foot drop.

This condition, which may be significantly disabling, is often preceded by a change in sensation in the same area (numbness, tingling, burning, or pain). These abnormal sensations can progress to muscle weakness, focal paralysis, and eventually to muscle wasting.

Recovery from this condition, caused by nerve infarction, can take months. In some cases, recoveries from mononeuritis multiplex are incomplete.

Figures of drop wrist and drop foot (courtesy of the University of North Carolina)

(Video of drop foot viewable on our Microscopic Polyangiitis page under classic symptoms.)

Laboratory Tests

Most laboratory findings in RV – for example, elevations in the erythrocyte sedimentation rate or C-reactive protein – are non-specific, and reflect the presence of a generalized inflammatory state. Hypocomplementemia, anti-nuclear antibodies (ANA), and atypical anti-neutrophil cytoplasmic antibodies (ANCA) are common.

Rheumatoid factor levels are usually extremely elevated. However, there is no definitive laboratory test for RV short of a tissue biopsy. The diagnosis must usually be made using a combination of history, physical examination, pertinent laboratory investigations, specialized testing (e.g.

, nerve conduction studies), and sometimes a tissue biopsy.

Because the treatment implications for RV are major, any diagnostic uncertainty must be met with definitive approaches to establishing the diagnosis. This usually involves biopsy of an involved organ. Deep skin biopsies (full-thickness biopsies that include some subcutaneous fat) taken from the edge of ulcers are very useful in detecting medium-vessel vasculitis.

Nerve conduction studies help identify involved nerves for biopsy. Muscle biopsies (e.g., of the gastrocnemius muscle) should be performed at the same time as nerve biopsies, to increase the chance of finding changes characteristic of vasculitis.

Imaging studies have no consistent role in the evaluation of RV, although sometimes angiography of the gastrointestinal tract is useful.

What Causes Rheumatoid Vasculitis?

The cause of RV is unknown, but given the prominence of immune components and the pathologic changes in involved blood vessels, an auto-immune process is suggested.

How is Rheumatoid Vasculitis diagnosed?

Most laboratory findings in RV – for example, elevations in the erythrocyte sedimentation rate or C-reactive protein are non-specific, and reflect the presence of a generalized inflammatory state. Hypocomplementemia, anti-nuclear antibodies (ANAs), and atypical anti-neutrophil cytoplasmic antibodies (atypical ANCAs) are common.

Rheumatoid factor levels are extremely elevated, as a rule. However, there is no definitive laboratory test for RV short of a tissue biopsy. The diagnosis must usually be made by the combination of history, physical examination, pertinent lab work, other specialized testing (e.g.

, nerve conduction studies), and sometimes even a tissue biopsy is required.

The diagnosis of RV should be considered in any rheumatoid arthritis patient who develops new constitutional symptoms, skin ulcerations, decreased blood flow to the fingers or toes, symptoms of a sensory or motor nerve dysfunction (numbness, tingling, focal weakness); or any inflammation of the lining around the heart or lungs (pericarditis or pleurisy/pleuritis).

Patients with a history of joint-destructive rheumatoid arthritis are at an increased risk for infection.

Therefore, when a rheumatoid arthritis patient presents with a new onset of non-specific systemic complaints an infection must first be eliminated.

Patients with rheumatoid arthritis typically have immune systems that are disordered from previous immunosuppression and underlying disease (e.g., joint damage). This patient population, therefore, is at higher risk of infection.

The differential diagnosis of RV includes:

  • Cholesterol embolization syndromes, in which a piece of cholesterol breaks off of a plaque, may cause digital ischemia (blood flow obstruction to a finger or toe), and a host of other symptoms that mimic vasculitis.
  • Diabetes mellitus is another major cause of mononeuritis multiplex, but multiple mononeuropathies occurring over a short period of time are unusual in diabetes.
  • Many clinical features of RV mimic those of polyarteritis nodosa, cryoglobulinemia, and other forms of necrotizing vasculitis. Therefore they too should be considered in this setting.

Because the treatment implications for RV are major, any diagnostic uncertainty must be met with a definitive approach to establishing the diagnosis. As alluded to earlier, this usually involves the biopsy of an involved organ.

Deep skin biopsies (full-thickness biopsies that include some subcutaneous fat) taken from the edge of ulcers are very useful in detecting medium-vessel vasculitis. Nerve conduction studies help identify involved nerves for biopsy. Muscle biopsies (e.g.

, of the gastrocnemius muscle) should be performed at the same time as nerve biopsies, to increase the chance of finding changes characteristic of vasculitis.

Imaging studies have no consistent role in the evaluation of RV, although sometimes angiography of the gastrointestinal tract is useful.

Normally, the cells of the blood vessel wall would be fewer in number (less thick) and the lumen (larger red area) would be larger. The arrow points (Figure 6, left) to an inflamed blood vessel found on a muscle biopsy. The globular pink areas are muscle fibers.

Treatment and Course of Rheumatoid Vasculitis

Therapy should reflect the severity of organ involvement. Prednisone or other steroid therapies are often the first line of treatment.

Optimizing treatment of the underlying rheumatoid arthritis is also essential, therefore medications such as methotrexate or tumor necrosis factor inhibitors may be employed.

In the setting of impending damage to major organs such as the eyes, a peripheral nerve, the gastrointestinal tract, or of a severe skin ulceration, cyclophosphamide is usually warranted.

What’s New in Rheumatoid Vasculitis?

Compared to other forms of vasculitis, there has been relatively little research in recent years on the specific entity of RV.

The lack of similarity in available reports on RV and discrepancies in case definitions have created challenge to building standard approaches to the diagnosis and treatment of this condition.

There is some evidence that the incidence of RV has decreased over the past several decades, perhaps because of better treatment of the underlying rheumatoid arthritis.


Epidemiology, Management, and Outcomes of Large and Small Native Joint Septic Arthritis in Adults

Septic Arthritis | Johns Hopkins Medicine

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Native joint septic arthritis (NJSA) is poorly studied. We describe the epidemiology, treatment, and outcomes of large joint NJSA (LNJSA) and small joint NJSA (SNJSA) in adults at Middlemore Hospital, Auckland, New Zealand.

This was a coding-based retrospective study of patients ≥16 years old admitted between 2009 and 2014. Prosthetic joint infections were excluded.

Five hundred forty-three NJSA episodes were included (302 LNJSA, 250 SNJSA). Only 40% had positive synovial fluid culture.

Compared to SNJSA, LNJSA has higher incidence (13 vs 8/100 000 person-years [PY]), occurs in older, more comorbid patients, and is associated with greater rates of treatment failure (23% vs 12%) and mortality, despite longer antibiotic treatment.

Total incidence is higher than previously reported (21/100 000 PY), with marked interethnic variation. Incidence rises with age (LNJSA only) and socioeconomic deprivation (LNJSA and SNJSA). Tobacco smokers and males are overrepresented. The most commonly involved joints were knee (21%) and hand interphalangeal (20%).

Staphylococcus aureus was the most common pathogen (53%). Mean antibiotic duration was 25 days for SNJSA and 40 days for LNJSA, and the mean number of surgical procedures was 1.5 and 1.6, respectively. Treatment failure was independently associated with LNJSA, age, intra-articular nonarthroplasty prosthesis, and number of surgical procedures.

This is the largest contemporary series of adult NJSA. SNJSA has better outcomes than LNJSA and may be able to be safely treated with shorter antimicrobial courses. Incidence is high, with significant ethnic and socioeconomic variation. Microbiological NJSA case ascertainment underestimates case numbers as it frequently excludes SNJSA.

septic arthritis, native joint, epidemiology, treatment, outcomes

Septic arthritis (SA) is uncommon, with reported incidence from 4 to 12/100 000 person-years (PY) [1–3]. Incidence varies by ethnicity [2] and increases with age [1, 3–5] and socioeconomic deprivation [6].

Recognized risk factors include rheumatoid arthritis, diabetes mellitus, hemodialysis, intravenous drug use, alcohol dependence, intra-articular steroid injection, joint surgery, cutaneous ulcers, and skin infections [1, 6, 7].

Despite associated mortality of 11%–19% [7–10] and poor functional outcomes in 24%–33% [7, 10–12], SA has been poorly studied in adults, with no randomized treatment trials [13], few prospective studies [6, 11, 14, 15] and generally modest-sized cohorts [1].

Study inclusion criteria are generally modifications of the Newman criteria [12]; however, many amalgamate native joint septic arthritis (NJSA) and total joint arthroplasty infections [2, 4, 7, 9, 14, 15] and both children and adults [2, 4, 7, 12, 16]. Small joint SA is even more poorly understood as most series are biased toward large joint infection either by requiring positive synovial fluid culture for inclusion [4–6, 9] or specific exclusion of small joints [12].

Middlemore Hospital (MMH) in South Auckland, New Zealand, is an 850-bed publically funded secondary and tertiary teaching hospital caring for an ethnically diverse, socioeconomically deprived [17] catchment of approximately 500 000 people. MMH provides plastic and hand surgery services to a wider region.

All services relevant to NJSA treatment (Orthopedic, Plastic and Hand Surgery, Rheumatology, Infectious Diseases, and Clinical Microbiology) are present at MMH and there are no other facilities ly to treat SA within this catchment area.

NJSA at MMH is managed by surgical services, and surgical intervention is the mainstay of invasive NJSA treatment (rather than repeated therapeutic joint aspiration).

We aimed to describe the epidemiology, management, and outcomes of large joint NJSA (LNJSA) and small joint NJSA (SNJSA) (excluding spine and temporomandibular joints) in adults admitted to MMH between 1 January 2009 and 31 December 2014.


We conducted a retrospective review of electronic documentation for patients meeting all of the following inclusion criteria: age ≥16 years; admitted to hospital for ≥24 hours during the study period with an SA-specific International Classification of Diseases, Tenth Revision, Australian Modification discharge code M00.0–M00.9.

Despite meeting these criteria, episodes were excluded from the study if any of the following criteria were met: solely spine or skull joint infection; solely prosthetic joint involvement; solely infection of joints previously arthrodesed or excised; diagnosis other than NJSA considered more ly by the investigator; documentation too poor to extract information; or duplicated coding of episodes.

Information gathered included demographic details, comorbidity (including electronic Charlson comorbidity score [18]), modified Newman criteria [1], clinical features, microbiology, medical and surgical treatment, and outcomes including mortality, relapse, reinfection, admission and surgery for ongoing septic arthritis, and hospital length of stay. Inclusion of episodes where common laboratory contaminant organisms were identified as microbiological causes was further reviewed by a single infectious diseases specialist (author S. M.).

Incidence was calculated using only MMH-catchment-resident episodes, and population data from the 2006 and 2013 New Zealand census [19]. Annual population growth was estimated using a compound exponential growth model.

Socioeconomic deprivation was measured using average 2006 New Zealand Deprivation Index (NZDep) score for the patient’s area unit of residence.

The NZDep score ranges from 1 (least deprived) to 10 (most deprived), and is derived from multiple parameters [20]. Area units are variably sized geographic areas, typically including hundreds to several thousand residents.

The population of each area unit aged ≥16 years was calculated and aggregated into NZDep quintiles to calculate deprivation-specific incidence.


Interphalangeal, metacarpophalangeal, metatarsophalangeal, acromioclavicular, and sternoclavicular joints were defined as small and all others as large. Joints were defined as prosthetic where one or more articular surface was replaced.

Relapse was defined as readmission for NJSA of the previously infected joint, with the same organism isolated or negative culture. Reinfection was defined as NJSA of the same joint caused by a different organism.

Definitive treatment route was defined as the route of NJSA antibiotic administration at discharge (or the major administration route used if treatment completed as an inpatient).

Treatment failure was defined as any of the following: death within 90 days of index admission; relapse; reinfection; amputation, excision arthroplasty, or arthrodesis of an involved joint for ongoing infection; or readmission to hospital for ongoing NJSA.

Statistical Analysis

Statistical analysis was performed using R version 3.1.2 [21] (R Core Team, Vienna, Austria), SAS version 9.4 (IBM Analytics, Armonk, New York), and Datadesk 6.3 (Data Description, Ithaca, New York) software.

Parametric and nonparametric tests were used to compare and test for association between the covariates and outcomes. Two-samples t test or Mann-Whitney-Wilcoxon U test was used for continuous variables. The χ2 or Fisher exact test was used for categorical variables.

Results were considered statistically significant if the P value was ≤ .05. Episodes with concurrent LNJSA and SNJSA were included in both groups.

Simple and multiple logistic regressions were carried out to investigate the association between outcomes and various factors. Prespecified interactions were tested for between the following: joint size and skin and soft tissue infection; joint size and definitive antibiotic route; β-lactam therapy and definitive antibiotic route; and joint size and number of surgical procedures.

Interactions found to be significant at the 5% level were accounted for in the full model. Model selection was performed Akaike information criterion (AIC) selection criteria and 5% significance level to derive the final reduced models.

Backward, forward, and stepwise methods were used to verify significant factors in the final reduced model.

Simple logistic regression models were carried out and a reduced model was obtained from the full model by removing covariates until the AIC could no longer be improved.


Inclusion data are shown in Figure 1. We identified 839 episodes and excluded 296 (35%) resulting in 543 NJSA episodes in 521 individuals. At least 1 modified Newman criterion [1] was met in 90% of episodes (490/543).

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Episode inclusions and exclusions.


Gum disease linked to rheumatoid arthritis • Johns Hopkins Rheumatology

Septic Arthritis | Johns Hopkins Medicine

A new study lead by Felipe Andrade, M.D., Ph.D.

from the Johns Hopkins University Division of Rheumatology provides new evidence that a bacterium known to cause chronic inflammatory gum infections also triggers the inflammatory autoimmune response also found in the joints of patients with the chronic, joint-destroying autoimmune disease, rheumatoid arthritis (RA). These new findings have important implications for the prevention and treatment of RA.

Why was this study done?

 Medical investigators have observed a clinical association between periodontal disease (gum diseases) and RA since the early 1900s, and over time, researchers have suspected that both diseases may be triggered by a common factor. However, our understanding of how these diseases may be related remained poorly defined.

How was this study done?

The study began by searching for common factors that may link periodontal disease and RA. Initial clues came from the study of periodontal samples, where the authors found that a similar process that had previously been observed in the joints of patients with RA was occurring in the gums of patients with periodontal disease.

This common process is called “hypercitrullination”. Citrullination occurs naturally in everyone as a way to regulate the function of proteins. However, in people with RA, this process becomes overactive, resulting in hypercitrullination and the abnormal accumulation of citrullinated proteins.

This drives the production of antibodies against these proteins that create inflammation and attack the joints in patient with RA.

What were the major findings?

Among different periodontal bacteria, the study identified that only one called Aggregatibacter actinomycetemcomitans (Aa) could trigger hypercitrullination in human white blood cells, the major source of citrullinated proteins in RA.

Aa causes hypercitrullination by secretion of a toxin called leukotoxin A (LtxA) that pokes holes in white blood cells as a self-defense strategy to kill host immune cells. Further studies demonstrated that almost half of the patients with RA have evidence of infection by Aa, compared with 11% of healthy individuals.

More strikingly, exposure to Aa was an important factor for production of antibodies to citrullinated proteins in patients with genetic susceptibility to RA.

What is the impact of this work?

Current treatment with steroids, biologic drugs and physical therapy are effective for reducing or slowing the crippling and painful joint deformities in some, but not all patients with RA.

This study sheds new light on the longstanding relationship between gum disease and RA by identifying hypercitrullination as a common process that unites these two seemingly unrelated conditions.

Learning more about how this process starts and causes the immune system to attack proteins in the joint may lead to new ways to treat and even prevent RA in the future.

This research was supported by:

Rheumatology Research Foundation, Fundación Bechara, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) under grant numbers R01AR069569 and AR050026-01, the National Institute of Dental and Craniofacial Research (NIDCR) under grant numbers DE021127-01 and R37 DE12354, and the Intramural Research Program of the NIDCR.

Link to original research article:

Aggregatibacter actinomycetemcomitans-induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis. Konig MF, Abusleme L, Reinholdt J, Palmer RJ, Teles RP, Sampson K, Rosen A, Nigrovic PA, Sokolove J, Giles JT, Moutsopoulos NM, Andrade F. Sci Transl Med. 2016 Dec 14;8(369):369ra176.


Computer algorithm could aid in early detection of life-threatening sepsis

Septic Arthritis | Johns Hopkins Medicine

For a patient with sepsis—which kills more Americans every year than AIDS and breast and prostate cancer combined—hours can make the difference between life and death.

Study author David Hager checks on a patient in the intensive care unit.

Image : Will Kirk / Johns Hopkins University

The quest for early diagnosis of this life-threatening condition now takes a step forward, as Johns Hopkins University researchers report on a more effective way to spot hospital patients at risk of septic shock.

The new computer-based method correctly predicts septic shock in 85 percent of cases, without increasing the false positive rate from screening methods that are common now.

“But the critical advance our study makes is to detect these patients early enough that clinicians have time to intervene,” says Suchi Saria, an assistant professor of computer science in Johns Hopkins' Whiting School of Engineering and of health policy in the Bloomberg School of Public Health. She led the study, published today as the cover story in the journal Science Translational Medicine.

More than two-thirds of the time, the method was able to predict septic shock before any organ dysfunction. That is a 60 percent improvement over existing screening protocols.

Peter J. Pronovost, a study co-author and senior vice president for patient safety and quality at Johns Hopkins Medicine, said the research promises significant progress in treating a condition that is estimated to hit about a million Americans and kill about 200,000 every year—many of them in hospitals and nursing homes.

“We know a lot of those deaths would ly be preventable” if sepsis were diagnosed well before it develops into septic shock and organ failure, said Pronovost, who directs the Armstrong Institute for Patient Safety and Quality at Johns Hopkins Medicine. “Right now, much of sepsis is invisible until someone is on death's door.” Every passing hour before sepsis patients receive antibiotics, he said, “correlates strongly with risk of death.”

Sepsis is caused by a powerful immune system reaction to infection that, if untreated, can cause inflammation throughout the body; the inflammation can trigger blood clots and leaking blood vessels.

That hinders blood flow, which in the worst cases causes organ failure. The condition is a significant problem among vulnerable populations in hospitals and nursing homes.

It can be triggered by invasive procedures, including catheterization.

The study drew on electronic health records of 16,234 patients admitted to intensive care units—including medical, surgical, and cardiac units—at Boston's Beth Israel Deaconess Medical Center from 2001 to 2007. Researchers created an algorithm that combines 27 factors into a Targeted Real-time Early Warning Score, or TREWScore, measuring the risk of septic shock.

“One strength of this approach,” notes Katharine Henry, a PhD student in Saria's lab and first author of the study, “is that all of our inputs are routinely collected. You don't need specialized new measurements.”

The method differs in several respects from previous attempts to predict septic shock. It's a larger data pool, takes account of more health indicators, and factors in several elements that could have confounded the results.

One question now is how TREWScore can be used in a hospital or nursing home. David Hager, a co-author and director of the Medical Progressive Care Unit at the Johns Hopkins Hospital, said the algorithm could be programmed into an electronic health records system to alert doctors and nurses about a patient at risk of septic shock.

“The tricky issue is thinking about how the clinical team is provided with the information,” Hager said. A hospital's electronic health records system could be set up to convey alerts to clinicians via pager or cellphone at regular intervals, he said.

“But we have to do this in a way that it is well-integrated into the existing clinical workflow and does not cause alarm fatigue,” Saria said. That is the focus of ongoing study.

Saria, whose lab is a center for big-data analysis of electronic health records, said the study is part of a broad effort at Johns Hopkins to help clinicians and patients by providing continuous, insightful monitoring.

“Our methods are reaching a point where they can be a real aid to clinicians,” she said, “especially in noticing subtle hints, buried deep in a chart, that a problem is developing.”

Pronovost said the effort seeks to make care safer and more humane for patients. That includes rethinking what harms are preventable. Before this, conditions sepsis were considered unavoidable.

“This is a culture change,” he said.

The research was supported by National Science Foundation Graduate Research Fellowship Award 1232825, Google Research grant 1202463721, the Gordon and Betty Moore Foundation, and Johns Hopkins Whiting School faculty start-up funds.