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88 Cards in this Set

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A chronic non-erosive deformity fo the hands that is reducible, because it is due to tendon inflammation rather than joint destruction; it is seen in SLE and Rheumatic Fever and is similar in appearance to rheumatoid arthritis
Jaccoud Arthropathy
A patient with SLE develops hematuria and proteinuria. What is the next step?
Biopsy and corticosteroids
What biomarkers correlate with disease activity in proliferative lupus nephritis?
Anti-dsDNA and Complement levels
After a diagnosis of lupus nephritis is made, what is the next step in treatment?
Start immunosuppressives (Cyclophosphamide or Mycophenolate mofetil)
Most frequent cardiac manifestation of SLE
Cardiac valve involvement (Libman Sacks) is strongly associated with what antibodies?
Antiphospholipid Antibodies
Autoantibody associated with Limited Progressive Systemic Sclerosis (CREST)?
anticentromere antibodies
Autoantibody associated with Granulomatosis with Polyangiitis (Wegener's)
What diseases do you suspect when pANCA is positive?
Microscopic Polyangitis or Churg Strauss
Auto-antibody associated with myositis?
Anti-Jo-1 Ab
Approximately what percentage of Rheumatoid Arthritis patients are RF negative?
Approximately 30% of RA patients are RF negative.

70% sensitivity for RA; not specific for RA.

RF is an antibody to Ig and hence many false positives (HCV, SLE)
Most specific autoantibody for Rheumatoid Arthritis?
Anti-cyclic citrullinated peptide is the most specific test for RA (similar sensitivity as RF ~70%).

Positive in up to 1/3 of RF negative RA patients.

Associated with erosions.

Predicts diseases progression in patients with undifferentiated arthritis.
Most sensitive antibody for drug-induced SLE?
Anti-histone antibodies (95% sensitivity)
Osteoporosis prevention in patients with long-term corticosteroid therapy?
Calcium, vitamin D, and (in most cases) a bisphosphonate are indicated to prevent osteoporosis in patients requiring long-term corticosteroid therapy.
T/F - ALL NSAIDs are associated with increased cardiovascular disease?

The only exception is Naproxen which may slightly reduce cardiovascular disease.
Prostaglandin type associated with most of the antiinflammatory and analgesic effects of NSAIDs, but also associated with GI distress (ulcers), kidney disease, and HTN?
Prostaglandin E2
T/F - COX2 selective inhibitors (E.g. Celcoxib, aka Celebrex) reduces GI distress but not HTN or kidney disease?

Because COX-2-derived prostaglandins participate in maintaining kidney function, selective COX-2 inhibitors are NOT safer for the kidney than nonselective COX-2 inhibitors and still may exacerbate kidney disease or HTN.
This agent is a folic acid antagonist; however, the mechanism of its benefit in rheumatic diseases may relate NOT to folic acid antagonism but to its ability to raise extracellular adenosine levels. This agent is also the gold standard therapy for rheumatoid arthritis and an important treatment for other forms of inflammatory arthritis and autoimmunity such as psoriatic arthritis, systemic vasclulitis, and polymyositis. Moreover, this agent is also toxic to the liver, an abortifacient, can cause nodulosis, and rarely pneumonitis.
This agent provides only modest benefit for rheumatoid arthritis but has an excellent side-effect profile. In patients with lupus, it may prevent disease flares and may reduce morbidity and mortality. The mechanism of action appears to involve inhibition of antigen processing and costimulatory activation. The most important toxicity is visual loss resulting from retinal pigment deposition. Although this occurrence is rare at the doses usually employed (200-400 mg/d), baseline and regular retinal examinations should be done. Although pregnancy category C, expert consensus states that this drug is relatively safe in pregnancy and should not be discontinued.
This drug is a congener of a salicylate and a sulfapyridine molecule. It is used in inflammatory bowel disease to deliver 5-aminosalicylate to the colon; in inflammatory arthritis, it may be the sulfapyridine moiety that has the disease modifying role (making it moderately effective in RA). Potential toxicities include GI symptoms, HA, agranulocytosis, hepatitis, and reversible oligospermia. It is considered safe in pregnancy.
This agent blocks pyrimidine biosynthesis and targets lymphocytes, which lack pyrimidine salvage pathways. It is roughly as effective as methotrexate for rheumatoid arthritis; its use in other diseases is less well explored. Toxicities include liver and hematopoietic abnormalities, infection, and interstitial lung disease. It is extremely teratogenic and must not be used during or prior pregnancy. Of note, this agent also has an extremely LONG HALF-LIFE and undergoes enterohepatic circulation. In the event that the drug must be withdrawn, a cholestyramine regimen (3x/daily x 8 days) must be used to remove the drug from the body. After cholestyramine treatment, levels must be measured twice to confirm removal of the drug.
This agent is typically used as a corticosteroid-sparing or as a maintenance agent in lupus, vasculitis, and polymyositis. Its metabolism involves the enzyme thiopurine methyltransferase (TPMT); patients with this enzyme deficiency are prone to toxicity with use of this drug (and some Rheumatologists advocate checking TPMT activity before administrating this drug). The metabolites of this drug are also degraded by xanthine oxidase; therefore, the drug should be avoided or used with great caution in patients taking allopurinol or febuxostat. This drug should not be employed routinely in pregnant patients.
This agent is a potent alkylating agent and has long been used to treat life-threatening lupus and systemic vasculitis. However, this potent immunosuppressant has numerous potential severe adverse events, including leukopenia, anemia, increased rate of bacterial and fungal infections, hemorrhagic cystitis and bladder cancer, lymphoma, and other long-term malignancies. Close monitoring with CBC and differential, Liver associated enzymes, and UA are required routinely. This agent is never used in pregnancy unless the life of the mother is at stake.
This agent was developed to prevent transplant rejection but has also been used to treat lupus, particularly lupus nephritis. Its active metabolite inhibits inosine monophosphate dehydrogenase (an enzyme in the purine sythetic pathway) and it preferentially inhibits T and B cell lymphocytes. Studies suggest this agent may be at least as effective as cyclophsophamide in the treatment of lupus nephritis and lupus maintenance but with fewer side effects. This agent is also increasingly used as a corticosteroid-sparing agent in conditions such as systemic vasculitis and polymyositis. It is teratogenic and cannot be used in pregnancy.
Mycophenolate Mofetil
This agent is an immunosuppressant agent that preferentially targets T cells and demonstrates efficacy in several rheumatic and autoimmune diseases, including RA, lupus, inflammatory myositis, psoriasis, pyoderma gangrenosum, and inflammatory bowel disease. Toxicity is relatively common (HTN, nephrotoxicity, tremor, hirsutism); therefore it is mainly used as a 3rd line agent in rheumatic diseases.
This is indicated prior to use of ALL biologic agents?
TB testing and vaccinations
This biologic agent has been shown to decrease disease activity and inhibit the progression of structural damage in RA, with the greatest efficacy observed when used in combination with weekly methotrexate. It is also highly effective in suppressing cutaneous and articular disease in psoriatic arthritis. Joint symptoms are improved in patients with ankylosing spondylitis, although treatment has not been sown to delay fusion of axial joints. The monoclonal antibody form of this agent is also beneficial in managing uveitis, oral and genital lesions of Behcet's disease, inflammatory bowel disease, and pyoderma syndromes. Clinical responses occur within weeks of initiating treatment. If infection occurs while on therapy, the agent should be held until resolution of the infection.
TNF-alpha inhibitors:

Etanercept (TFNR:Fc);
Infliximab (anti-TNF-alpha mAb);
Adalimumab (anti-TNF-alpha mAb);
Certolizimab (anti-TNF-alpha pegol);
Golumumab (anti-TNF-alpha mAb);
A fusion protein of CTLA4, a molecule expressed on activated human T cells and the Fc portion of IgG. This agent is useful in RA and binds to antigen-presenting cells and blocks costimulatory signals to T lymphocytes. It is given in monthly IV infusions. The time to maximum clinical response is 6 months (longer than TNF-alpha inhibitors). It is recommended for patients with moderate or high disease activity and poor prognostic features who have had an inadequate response to sequential nonbiologic DMARDs or methotrexate in combination with other DMARDs and is also effective in patients who have had an inadequate response to TNF-alpha inhibition. The agent may be associated with increased risk of lymphoma, lung cancer, as well as COPD flares. It should not be used concurrently with other biologic agents.
This agent is a chimeric monoclonal antibody that depletes CD20 B cell lymphocytes. Depletion of CD20 B cells from the peripheral blood is rapid and persists for 6-12 months. In placebo-controlled studies, peripheral B-cell depletion using this drug was associated with improvement in disease activity measures as well as reduction in joint erosion development in patients with RA. The drug is currently approved for use in combination with methotrexate in patients who have not adequately responded to TNF-alpha inhibitor therapy. This agent is also as effective as cyclophoshamide in patients with ANCA-associated vasculitis. Placebo-controlled trials show no efficacy of this drug in SLE. Of note, there has not been associated increase of infections with this agent. However, severe infusion reactions can occur, and rare cases of progressive multifocal leukoenceophalopathy associated with JC virus reactivation have been reported.
An IV chimeric IL-6 monoclonal antibody drug that attenuates B and T lymphocyte activation, leukocyte migration, osteoclast activation, and hepatic synthesis of acute phase reactants. It is FDA approved for RA who have experienced inadequate responses to TNF-alpha inhibitors. It is associated with leukopenia, thrombocytopenia, and elevated serum aminotransferase levels. Serum lipid levels are increased frequently and should be monitored. Reactivation of TB and invasive fungal infections can occur and rare instances of gastric and intestinal rupture have been reported.
A human genome-derive monoclonal reagent with specificity for the p40 subunit shared by IL-12 and IL-23. Blocking IL-12 attenuates the maturation and activation of the Th1 lineage of T cells responsible for elaboration of inflammatory cytokines, including TNF-alpha and interferon-gamma; blocking IL-23 attenuates the maturation and survival of Th17 cells, a subset of T-cells implicated in the pathogenesis of several autoimmune disorders, including Crohn's disese, psoriasis/psoriatic arthritis, and rheumatoid arthritis. Higher than expected rates of infection or malignancy have yet to be observed in use of this biologic agent.
A monoclonal antibody with specificity for B cell activating factor (BAFF), also referred to as B-lymphocyte stimulator (BLyS). BAFF mediates the maturation and survival of immature B cells to antibody-secreting plasmablasts, and its levels are elevated in patients with SLE and Sjogren syndrome. It has been FDA approved for treatment of SLE based on demonstrated decreases in autoantibody titers and disease activity measures.
This agent is a purine analog that inhibits xanthine oxidase and thereby blocks urate production. It lowers hyperuricemia regardless of the cause of hyperuricemia. Side effects include rash, bone marrow failure, hepatic failure, and Stevens-Johnson Syndrome. It should be discontinued immediately in patients who develop a rash, although desensitization is possible. This drug can be used in kidney disease so long as it is started at a low dose and titrated up until urate target goals are achieved (but not exceeded). It should be avoided or used with extreme caution in patients taking another purine analog such as azathioprine or 6-mercaptopurine.
This agent is a xanthine oxidase inhibitor used to lower uric acid and is FDA approved for patients with moderate kidney failure. Its toxicities include liver function abnormalities, which are often transient. It should not be used in patients taking 6-mrcaptopurine or azathioprine.
This agent inhibits the renal tubule transporter URAT1 to block retention of urate. It is only effective in patients who underexcrete uric acid (documented after 24-hour urine collection) and is ineffective in patients with kidney disease. This agent increases the risk of kidney stones, therefore, patients must be advised to hydrate aggressively, and the drug should be avoided in patients at high risk for kidney stones (e.g. in patients with prior stones or tophaceous gout).
A fungally derived uricase that is used to prevent or treat tumor lysis syndrome. However, this agent is HIGHLY IMMUNOGENIC and is not an option for chronic use.
A pegylated recombinant mammalian uricase that has received FDA approval for treatment-failure gout. Less immunogenic, but allergic and anaphylactic reactions may still occur. It rapidly decreases serum uric acid levels and may help resolve tophaceous deposits.
Hormonal influence on the development of Rheumatoid Arthritis
Risk is reduce in women who have had children and have breast-fed for >1 year. Disease activity often subsides in pregnancy but flares post-partum. Men with RA usually have lower levels of androgenic hormones and higher concentrations of estradiol.
A modifiable risk factor for developing rheumatoid arthritis?
Smoking cessation
The "shared epitope" that is a strong risk factor for Rheumatoid Arthritis?
HLA-DRB chains (DR4, DR14, and DR1)
A symmetric polyarthritis involving small, medium, and large joints that is associated with prolonged (>1 hour) morning stiffness. The metacarpophalyngeal and proximal interphalangeal joints of the hands; the rists, and the metatarsophalangeal joints of the feet are almost always affected. The distal interphalangeal joints and the lumbar spine are spared. The shoulders, elbows, hips, knees, ankles, and cervical spine are commonly involved. Examination reveals soft, boggy, or fluctuant swelling and tenderness at involved joints. Warmth and redness are not always present. With active joint inflammation, there is pain on active and passive motion, and range of motion may be limited. Deformities occur over time and carpal tunnel syndrome is common.
Rheumatoid Arthritis
Stigmata of RA hand involvement
RA vs. OA
Rheumatoid arthritis patient who develops pancytopenia, splenomegaly, and leg ulcers
Felty Syndrome
Factors associated with poorer outcomes in patients with rheumatoid arthritis?
Early joint erosions, an increased number of affected joints, elevation in ESR or CRP levels, the presence of rheumatoid nodules, and greater functional impairment.
Is there value in frequent X-rays of joints in patient's with RA after the diagnosis is made?
Yes! Radiographic monitoring of patients with rheumatoid arthritis allows for assessment of joint-space narrowing or erosion; progressive joint damage on plain radiographs is evidence of an insufficient therapeutic regimen.
Prior to intubation for an elective surgery in a patient with rheumatoid arthritis, what must be done first?
Obtain C-spine (Extension/Flexion) X-rays to assess C1-C2 subluxation. Prevents cord compression during intubation.
Initial monotherapy for patients with rheumatoid arthritis of any duration or degree of activity
Methotrexate or Leflunomide
This class of biologic agents can be used in conjunction with non-biologic DMARDs in treatment of Rheumatoid Arthritis with moderate-to-high disease activity?
TNF-alpha inhibitors. Of note, patients who do not respond to one agent in the class can benefit from another agent in the class.
Perioperative medication management in RA?
Stop NSAIDs, Continue Methotrexate (helps prevent post-op flares and does not increase infection risk), and Hold TNF-alpha inhibitors (increases post-op infections).
Medication management in pregnant patients with Rheumatoid Arthritis
Methotrexate must be discontinued 3 months prior to conception. Leflunomide also must be discontinued >3 months prior to conception and cholestyramine may be used to hasten the elimination from the body. Sulfasalazine causes reversible oligospermia in men and should be discontinued 3 months prior to planned conception. NSAIDs and ASA may interfere with implantation when taken during early pregnancy. NSAIDs can be used in the second trimester but should be avoided in the third trimester due to risk of premature closure of the ductus arteriosus and labor difficulties. Corticosteroids are frequently used but should be avoided if possible before 14 weeks of gestation because of the risk of cleft palate. Corticosteroid use is strongly associated with gestational diabetes and HTN. Hydroxychloroquine and sulfasalazine are considered safe in pregnancy. Uncertainty remains on use of TNF-alpha inhibitors in pregnancy, and are usually held prior to conception. Placental antibody transport can lead to levels of monoclonal antibodies that are higher in cord blood than in the mother. NSAIDs and low dose prednisone are considered safe during lactation, but methotrexate should be avoided.
The strongest risk factors for osteoarthritis
Advancing age, obesity, female gender, joint injury, and genetic risk factors. Risk factors vary somewhat on the joints involved. For example, obesity is the most important modifiable risk factor for knee OA. The prevalence of OA of the hip and knee are 2x higher in women than men. OA of the hand has strong female and genetic predilections; it is also associated with obesity, suggesting that the effects of obesity may be metabolic or cytokine-driven as well as mechanical.
Morning stiffness in OA?
Usually lasts <30 minutes
Classic features of OA in the hand
Additionally, "squaring" of the carometacarpal joint may occur in OA.
Classic features of Knee OA
Assymetric joint-space narrowing of hte knee can result in valgus (lateral joint-space narrowing and knocked knee) or varus medial joint space narrowing and bow-legged) deformities. During normal gait, the patient's center of gravity focuses over the medial tibiofemoral joint. Therefore medial joint-space narrowing is the more common OA findings in patients with knee OA.
Osteoarthritis of the spine
OA of the spine may lead to loss of spine monility. Foraminal or canal stenosis can develop as a result of bone spurs or disk degeneration (resutling in disk bulges or fragmentation), leading to nerve root impingement (cervical radiculopathy, sciatica, pseudoclaudication [from lumbar spinal stenosis], or myelopathy [from cervical spinal stenosis]).
Idiopathic arthritis that generally affects the axial skeleton, weight-bearing joints (hips and knee), and hand (proximal and distal interphalangeal and carpometacarpal joints). Onset can begin as early as the 4th decade, and prevalence increases steadily with age. Women and black persons have higher prevalence rates.
Primary Osteoarthritis
What should be considered if OA is found on an atypical joint (such as the metacarpophalangeal joints)?
Consider metabolic diseases such as Hemochromatosis or other metabolic diseases. The next step is to order iron studies and genetic tests.
This type of osteoarthritis typically involves the hands and occurs predominantly in women. Flares of joint inflammation involve the proximal and distal interphalangeal joints and are associated with erythema, swelling, and severe pain. Radiographs reveal erosions of these joints as well as bone spurs and ankylosis.
Erosive Osteoarthritis
Characterized by calcification of the spinal ligaments, which causes large, flowing osteophytes. Typically there is little disk-space narrowing. Thoracic involvement is common. Also causes calcification of the entheses (where tendons or ligaments insert into bone), which may result in Achilles or calcaneal spurs as well as "whiskering" (calcification of the origin of the quadriceps muscles along the iliac crest). Most commonly occurs in obese men older than 40 years of age. Patients may be asymptomatic or describe stiffness and reduced range of motion, particularly at the thoracic spine. Some studies demonstrated elevated IGF-1 and GH in these patients. Diagnosis is made by the presence of flowing osteophytes across 4 contiguous vertebrae. Unlike Ankylosing spondylitis, there should not be sacroiliitis or vertical bridging syndesmophytes.
Diffuse Idiopathic Skeletal Hyperostosis (DISH). There is flowing ossification (black arrows) that spans more than four contiguous vertebral bodies while the disc height is maintained and the flowing ossification is separated from the anterior aspect of the vertebral body (blue arrows).
Radiographic findings in patients with OA
Joint-space narrowing, osteophytes, subchondral sclerosis, bone cyst formation, and eburnation. Radiographic severity does not correlate with severity of symptoms.
This trial examined the impact of weight loss, exercise, or combination therapy vs. general healthy lifestyle recommendations in patients with OA. The diet and exercise groups showed significant improvement in pain, function, walking distance, and stair climbing at 6 months that persisted after 18 months, with the greatest improvements seen in those using combination therapy with weight loss and exercise.
ADAPT (Arthritis, Diet, and Activity Promotion Trial)
First line pharmacologic therapy for OA
Acetaminophen. NSAIDs should be reserved for those who doe not respond to Acetaminophen. There have been mixed results about the effectiveness of glucosamine and chondroitin (Larger nonindustry sponsored trials and meta-analyses fail to show benefit). Topical creams, including anti-inflammatory agents (methyl salicylate, diclofenac), capsaicin, or other modalities (irritant oils to provide heat and evaporating creams to provide cold), can provide symptomatic relief. Lidocaine patches have been shown to be helpful for knee OA. There should be judicious use of opioids in patients with OA.
When are intra-articular joint injections indicated in OA?
When a single joint or a few joints cause pain that is disproportionate to other joints and limits function, intra-articular corticosteroids may be effective in providing pain relief and improving function. The amount and duration of pain relief vary by patient and there is no good method for identifying who might respond well. Successful injections provide pain relief for an average of 3 months. Risks of injections, including pain, bleeding, and infection, should be discussed. Potential long-term risks from repeated injections may occur, including atrophy of the cartilage; therefore, the general recommendations calls for no more than 3 injections per year in a single joint. Rare adverse effects include fat atrophy and depigmentation of the skin. Hyaloronic injections are expensive but provide similar pain relief to corticosteroid injections; however, pain relief can last longer (3-6 months), and there are no limitations on repeat injections. Pain relief typically begins after the series of injections has been completed. Hyaluronic acid injections are most effective when injected into a dry joint after the effusion is drained.
Cornerstone of Fibromyalgia Treatment
Related comorbidities, including sources of pain, sleep disruption, and mood disorders, must be addressed when establishing treatment modalities for patients with fibromyalgia. Nonpharmacologic therapy such as regular aerobic exercise, physical therapy, and cognitive behavioral therapy is the cornerstone of fibromyalgia treatment and should be initiated in all affected patients. Various SNRIs (duloxetine, and milnacipran), anti-epileptics (gabapentin, pregabalin), and TCAs (Amytriptaline), and Cyclobenzaprine are effective pharmacologic agents.
What is the strongest genetic risk factor for spondyloarthritis?
What is the next step when there is a sudden onset or unexplained worsening of psoriatic arthritis or reactive arthritis?
HIV testing
Characteristic features of spondyloarthritis
Axial/Peripheral arthritis, enthesitis, and dactylitis are common, as well as dermatologic, ophthalmologic, and GI inflammation.
Dermatologic finding associated with Reactive Arthritis. The appearance is usually of a vesico-pustular waxy lesion with a yellow brown colour. These lesions may join together to form larger crusty plaques with desquamating edges.
Keratoderma blenorhagicum
What is the next step (if any) if a patient with ankylosing spondylitis experiences back pain that is new, worsening, or different in character?
Spine imaging
What can the modest increase in mortality associated with ankylosing spondylitis be attributable to?
Secondary amyloidosis, Cardivascular complications, accidents, suicide
Classic findings spinal stigmata of Ankylosing Spondylitis
Association between psoriasis and gout
Skin cell turnover in psoriasis increases the risk for gout
Approximately what percentage of patients with psoriasis develop psoriatic arthritis?
Specific nail findings in psoriasis?
Nail pitting in psoriasis
Radiographic findings in Psoriasis
What does anti-CCP antibodies in Psoriatic Arthritis indicate?
Correaltes with erosive disease. Present in 5-15% of patients with psoriatic arthritis.
The coexistance of erosive or lytic changes with new bone formation at the etheses is characteristic of what type of arthritis?
Psoriatic arthritis
What percentage of patients with Inflammatory Bowel Disease develop MSK findings?
50%. Rarely arthritis develops prior to GI manifestations. Peripheral arthritis may be acute and remitting with a pauciarticular distribution commonly involving the knee. It usually occurs early in the course of the bowel disease, correlates with bowel inflammation, and resolves without specific intervention or destruction to the joints. Axial involvement occurs in up to 20% of patients, particularly in men. Patients may develop radiographic sacroiliitis and spondylitis with or without inflammatory back pain. Axial disease does not to parallel intestinal disease. Enthesitis develops in 10% of patients.
Postinfectious aseptic arthritis with a class triad of arthritis + uveitis + urethritis (in 1/3 of patients).
Reactive Arthritis
Who should spondyloarthritis be considered in?
Any inflammatory back pain <45 years old.
What is the initial imaging of choice in suspected spondyloarthritis?
A single anteroposterior radiograph of the pelvis - provides a view of the sacroiliac joints and the hips
If plain radiographs are negative, and spondyloarthritis is suspected, what is the next step?
MRI is the preferred alternative study for detection of inflammation of the sacroiliac joints if spondyloarthritis is highly suspected by plain radiographs are negative.
First-line therapy for patients with spondyloarthritis
If NSAIDs and steroids are not affective in treating spondyloarthritis, what is the next step?
TNF-alpha inhibitors are beneficial for patients with spondyloarthritis who have severe or persistent axial, peripheral, or extra-articular manifestations.
In patients with spondyloarthritis, what call of drugs can be helpful in peripheral arthritis but play no role in the management of axial manifestations?
Nonbiologic DMARDs (e.g. Methotrexate, or Sulfasalazine).
When C. trachomatis infection is detected in a patient with reactive arthritis, what is the next step?
Antibiotic treatment is indicated for the patient and his or her sexual partners to avoid reinfection or spread of the infection. A recent study reported improved clinical outcomes with prolonged combination antibiotic treatment for patients with reactive arthritis and evidence of persistent chlamydial joint involvement.
When should you give antibiotics in a patient with reactive arthritis caused by an enteric infection
Only if there is an active infection present. Antibiotic treatment is not indicated for patients with reactive arthritis caused by enteric infection that is resolved.