Rheumatology Pearls
  • Musculoskeletal side effects are seen in 40 to 60% of patients taking aromatase inhibitors like anastrozole
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  • Sudden flank pain and worsening proteinuria in a lupus patient with known glomerulonephritis should be assessed for renal vein thrombosis.
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  • IL-23, along with IL-1 and IL-6, drive the differentiation of Th17 cells. Th17 cells are defined by the production of the cytokine IL-17
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  • Postglucocorticoid hypopigmentation of the skin can be avoided by the injection of air following the medication.
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  • All patients with fibromyalgia should be asked about symptoms of sleep apnea. Physical therapy and amitriptyline won’t work unless corrected
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  • The length of a cane should produce 20–30° of elbow flexion when the cane is planted approximately 6 inches lateral to the 5th toe.
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  • New unexplained pain located above the neck in a patient over 60 years old should suggest the possibility of giant cell arteritis.
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  • TRAPS patients (TNF receptor-assoc. periodic syndrome) experience attacks of fever, migratory rash, and periorbital edema, lasting 1-3 weeks
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  • Anti-TIF1-gamma autoantibody positive dermatomyositis patients carry an increased risk for internal malignancies.
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  • The malar rash of SLE is not transient. Because inflammation takes time to resolve, lupus rashes do not resolve within hours.
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  • Ferguson views (plain radiograph) are useful for evaluation of the entire length of the sacroiliac joints symmetrically.
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  • Interstitial nephritis, manifest as a type 1 renal tubular acidosis, is the most common renal manifestation of Sjögren's syndrome.
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  • Lupus anticoagulant has the most significant odds ratio for the occurrence of CVA, not ACA or anti-prothrombin.
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  • PMR occurs in about 50% of patients with GCA, while approximately 15 to 30% of patients with PMR eventually develop GCA.
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  • The ANCA-associated vasculitidies (Wegener's, Churg Strauss, & MPA) are all associated with a pauci-immune glomerular nephritis.
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  • TRAPS patients (TNF receptor-assoc. periodic syndrome) have a mutation in the TNFRSF1A (TNF receptor) gene.
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  • The ARB (angiotensin receptor blocker) losartan has a uric acid-lowering effect.
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  • Felty’s syndrome is characterized by rheumatoid arthritis, splenomegaly and leukopenia with associated recurrent infections.
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  • Class IV lupus nephritis (diffuse proliferative) is the renal lesion associated with the highest morbidity and mortality for lupus patients.
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  • Two alleles, DRB1*0401 and DRB1*0404, primarily account for the DR4 association with rheumatoid arthritis in Caucasians.
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  • On a worldwide basis, the most common cause of Erythema nodosum is streptococcal infections (~20% of patients).
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  • Most polymyalgia rheumatica (PMR) patients demonstrate striking improvement in their symptoms with 24 to 48 hours of beginning steroids.
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  • Diplopia caused by ischemia of extraocular muscles, cranial nerves, or the brainstem may be a feature of GCA in up to 15% of patients.
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  • Trimethoprim/sulfamethoxazole can enhance the cytotoxic effects of methotrexate because trimethoprim is an antifolate reductase inhibitor.
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  • When getting a skin biopsy for Henoch Schönlein Purpura (HSP), make sure to send a sample for immunofluorescence looking for IgA deposits.
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  • Femoroacetabular impingement syndrome can be a cause of hip pain and premature osteoarthritis in young adults. Refer to an orthopedist.
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  • Eye involvement is common in spondyloarthropathies and usually involves the middle layer of the eye-uveal tract
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  • Patients with ANCA negative Churg-Strauss syndrome are more likely to have cardiac and parenchymal lung disease.
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  • In patients with psoriasis, nail changes have the strongest association with arthropathy, particularly affecting the DIP joints.
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  • In Wegener's granulomatosus, a lung biopsy is the most likely site to detect the diagnostic triad of vasculitis, granulomata, and necrosis.
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  • Hypercalcemia occurs in 10% of patients with sarcoidosis and is caused by endogenous production of 1,25 OH Vit D in the sarcoid granuloma.
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  • In Duchenne muscular dystrophy, there is a characteristic hypertrophy of the calves but no muscle tenderness.
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  • Anti-MDA5 autoantibodies are associated with amyopathic dermatomyositis. Patients are at increased risk for rapidly progressive ILD.
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  • Anserine bursitis is a major cause of knee pain in some patients with osteoarthritis of the knee.
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  • There are currently 5 FDA approved anti-TNFα agents: infliximab, etanercept, adalimumab, golimumab, and certolizumab pegol.
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  • Leflunomide (pregnancy category X) is detectable in plasma up to 3 years after discontinuation. Cholestyramine is given to enhance clearance
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  • Independent predictors of disease activity in pts w/ lupus include age, renal activity, immunosuppressant use and pre-existing organ damage
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  • Palindromic rheumatism - episodic inflammation in usually 2 to 3 joints, large joints commonly. There is no joint damage after attacks.
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  • Multicentric reticulohistiocytosis is characterized by severe destructive arthritis and cutaneous papulonodular lesions.
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  • The 5 types of psoriatic arthritis are: symmetric, asymmetric, distal interphalangeal predominant, spondylitis, and arthritis mutilans.
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  • In acute gonococcal septic arthritis, GC is rarely seen on gram stain or by culture. Furthermore, low WBC counts on synovial fluid do occur.
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  • Respiratory involvement (glottis or tracheobronchial tree) is a frequent finding in relapsing polychondritis and is the main cause of death.
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  • Limited joint mobility in a patient with diabetes mellitus indicates increased risk for microvascular disease, especially retinopathy.
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  • Paresthesia (burning) or hypesthesia (numbness and tingling) over the upper outer thigh is the classic presentation of meralgia paresthetica
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  • Rule out vitamin D insufficiency/ deficiency in patients losing bone mineral density while receiving therapy for osteoporosis.
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  • MCTD combines features of scleroderma, myositis, SLE, and RA and most patients are positive for the anti-U1-RNP autoantibody.
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  • Marfan syndrome results from mutations in the fibrillin-1 (FBN1) gene on chromosome 15, which encodes for the glycoprotein fibrillin.
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  • Pulmonary HTN & interstitial lung disease are under recognized complications of systemic JIA that are frequently fatal http://bit.ly/13WQNuA
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  • Mi-2 antibodies are seen in patients with “classic” dermatomyositis, including Gottron’s papules, heliotrope rash, & “V” and “shawl” sign.
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  • If a patient with PMR consistently requires > 20 mg of prednisone a day to control the disease symptoms, the diagnosis is probably wrong.
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  • In lupus patients, IRF5, IRAK1, and STAT4 genes are important for dendritic cell type I interferon production.
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  • NOMID (neonatal onset multisystem inflammatory disease) symptoms include rash, arthritis, & chronic meningitis leading to neurologic damage.
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  • Pericarditis often presents early in rheumatoid vasculitis. Its development should trigger an evaluation for other hallmarks of vasculitis.
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  • Post-steroid injection flares are likely due to crystallization of the steroid within the joint. Pain usually resolves within 1-2 days.
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  • Patients with polymyositis and anti-SRP antibodies have more cardiac involvement, a poor prognosis, and a poor response to therapy.
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  • C-reactive protein is normal in ~ 70% of patients w/ rheumatoid arthritis early in the disease course and even if elevated is non-specific.
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  • Lateral epicondylitis is also known as tennis elbow. Medial epicondylitis is also known as golfer's elbow.
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  • Indications for urate lowering therapy include tophaceous gout, erosive changes on xray, nephrolithiasis, & 2 or more gout attacks per year.
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  • Kienbock's disease is also known as avascular necrosis of the lunate bone (wrist), or lunatomalacia.
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  • Patients with “rhupus” have an overlap syndrome with clinical and serologic signs of both SLE and RA, including radiographic erosions.
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  • Denosumab is a monoclonal antibody targeted against RANK ligand and is FDA approved for the treatment of osteoporosis.
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  • About 10% of patients with giant cell arteritis GCA have upper respiratory symptoms including a sore throat and nonproductive cough.
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  • Systemic AA amyloidosis is the most devastating long-term complication of FMF. Outcomes include nephrotic syndrome & chronic renal failure
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  • Reactive arthritis appears to be triggered by CD8+ T cells responding to peptides derived from bacteria which are bound to HLA-B27.
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  • 10–20% of patients with Sjögren’s syndrome have anti-thyroglobulin antibodies and may go on to develop autoimmune thyroiditis.
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  • The risk of lupus panniculitis is associated with discoid lupus, leg ulcers, serositis, and myositis, but not proteinuria. #ACR2012
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  • Patients who have cold agglutinin syndrome frequently present with a low-grade autoimmune hemolytic anemia and acrocyanosis.
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  • PML should be considered in lupus patients with progressive neurologic deficits especially if immunosuppression is ineffective.
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  • About 7% of patients with polyarteritis nodosa (PAN) have hepatitis B virus (HBV), but fewer than 1% of patients with HBV develop PAN.
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  • Purpura, hypocomplementemia, and cryoglobulinemia are three key prognostic factors for adverse outcome in primary Sjogren's Syndrome.
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  • Clubbed fingers & tender periostitis of lower extremities can be clinical signs of a lung tumor. Hypertrophic Osteoarthrophathy
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  • The ENA 4 is comprised of four tests: anti-Sm, anti-RNP, anti-La, & anti-Ro. Often used in the evaluation of connective tissue diseases.
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  • Patients with DRESS syndrome often have a prolonged course with frequent relapses despite the discontinuation of the culprit drug
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  • Superior migration of the humeral head detected by plain radiography indicates a significant rotator cuff tear.
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  • The DAS28 is an index of RA disease activity. Calculated using a 28 tender & swollen joint count, ESR (or CRP), & patient global health VAS.
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  • Sparing of the epidermis and presence of mucin deposits differentiate scleromyxedema (lichen myxedematosus) from scleroderma and morphea.
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  • Approximately 33% of lupus patients stop working within 4 years of their diagnosis due to disability.
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  • Discoid lesions in children and adolescents are likely secondary to SLE, not to isolated discoid lupus.
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  • Lupus pernio is a chronic raised indurated skin lesion associated with sarcoidosis. It has nothing to do with either lupus or pernio.
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  • Rheumatoid arthritis can be seen in patients with T-cell large granular lymphocyte leukemia (T-LGL). Presentation is similar to Felty's.
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  • Belimumab is the first biologic therapy approved for the treatment of lupus. It is a monoclonal antibody which targets the cytokine BLyS.
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  • Melanonychia, or nail hyperpigmentation, is a well-described reversible adverse effect of cyclophosphamide.
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  • Patrick's test is useful in evaluating pathology of the hip. A positive test can be indicative of a sacroiliac problem but not very reliably
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  • Cochicine-induced axonal neuromyopathy most commonly occurs when renal dysfunction is present, but it is reversible not permanent.
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  • The most common infections preceding reactive arthritis are Chlamydia, Salmonella, Shigella, Campylobacter, and Yersinia.
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  • Hand deformity in SLE (Jaccoud’s arthropathy) results from ligamentous laxity rather than the destructive synovial pannus of RA.
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  • The leading cause of death in patients with diffuse systemic sclerosis is interstitial lung disease.
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  • A greater than 4% decline per year in bone mineral density on DEXA suggests treatment failure.
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  • Lupus patients should avoid sulfa-containing antibiotics because of a high incidence of skin rash & other side effects including lupus flare
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  • Leflunomide (rheumatoid arthritis DMARD) works by inhibiting dihydroorotate dehydrogenase (enzyme involved in de novo pyrimidine synthesis).
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  • Skin biopsy can confirm a diagnosis of calciphylaxis but carries a significant risk of severe pain, poor healing, and superinfection
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  • Lupus anticoagulant is an immunoglobulin that interacts with platelet membrane phospholipids, increasing adhesion & aggregation of platelets
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  • NOMID (neonatal onset multisystem inflammatory disease) can result from a mutation in the CIAS1 gene, which helps control inflammation.
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  • The use of azathioprine & allopurinol together can lead to a severe drug–drug interaction. It is usually better not to use this combination.
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  • Compared to the general population, there is a substantial increase in the male-to-female ratio in children born to women with SLE. #ACR2012
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  • Rheumatoid arthritis is currently one of the most frequent causes of amyloidosis of the AA type, however the prevalence is declining.
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  • Several clinical trials have demonstrated the benefit of quadriceps strengthening on pain and function in patients with OA of the knee.
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  • ALPS (autoimmune lymphoproliferative syndrome) is a disorder of the Fas-Fas ligand pathway that leads to a defect in lymphocyte apoptosis.
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  • Isolated patello-femoral compartmental degenerative changes in the knee is an important indicator of CPPD. (submitted pearl - thanks!)
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  • Pronator teres syndrome results from median nerve entrapment at the elbow - frequently accompanied by weakness of the index & middle fingers
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  • Dupuytren's contracture is progressive fibrosis of the palmar fascia resulting in contractures of one or more fingers at the MCP joints.
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  • The arthropathy associated with hyperparathyroidism is characterized by subperiosteal bone resorption of the middle phalanges.
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  • A prolonged aPTT suggests the possibility of an lupus anticoagulant (LA), but only about half of all patients with LA have an abnormal aPTT.
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  • Radiology findings in Wilson’s disease can reveal premature osteoarthritis, chondrocalcinosis, and chondromalacia patella. Knees most common
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  • In pregnant SLE patients who are flaring, starting azathioprine may not be all that effective. Better when started before. Pred still best.
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  • Trigger finger (aka stenosing flexor tenosynovitis) is noninfectious inflammation of the flexor tendon sheath of the finger (or thumb).
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  • Rheumatoid vasculitis overlaps substantially with polyarteritis nodosa and tends to affect the same types of organs.
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  • In any patient w/ patellofemoral disease, rule out hypermobility & pes planus. If present, shoe orthotics are a necessary part of therapy.
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  • Acetaminophen (Tylenol) potentiates the anticoagulant effect of coumadin so use caution with prescribing both.
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  • Calciphylaxis is a rare, painful disorder of metastatic calcification most commonly occurring in patients with ESRD on dialysis
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  • Children with SLE often require higher doses prednisone than their adult counterparts because of rapid drug metabolism (2 mg/kg vs 1 mg/kg).
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  • Approximately 10-15% of arthroplasties fail, the most common cause for which is osteolysis (inflammation initiated by arthroplasty debris)
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  • In children, Henoch Schönlein Purpura (HSP) is usually benign and self-limiting, however in adults, can be severe with worse outcomes.
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  • Leflunomide is known to cause significant increases in systolic and diastolic blood pressures within 2–4 weeks of initiation.
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  • Zidovudine induced myopathy causes myalgias, muscle tenderness, proximal muscle weakness, & muscle atrophy. CPK levels are elevated 10 fold.
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  • Diabetic cheiroarthropathy is a common complication of diabetes related to increased glycation and nonenzymatic browning of skin collagen.
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  • Infection with parvovirus B19 has been associated with symmetrical polyarthralgia/ polyarthritis which can mimic rheumatoid arthritis.
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  • Familial CPPD is associated with a gain of function of the ANKH gene product, leading to increased extracellular pyrophosphate.
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  • GI involvement occurs in ~50% of patients with polyarteritis nodosa (PAN) (with gallbladder and small bowel the most frequently involved).
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  • Acquired factor VIII inhibitor (aka acquired hemophilia A) is a complication of severe rheumatoid arthritis and systemic lupus erythematosus
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  • The most frequent ocular manifestation in patients with Cogan syndrome is interstitial keratitis. Tx is with steroids and immunosupprants
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  • Up to 80% of Stiff Person Syndrome (SPS) patients have an autoantibody against glutamic acid decarboxylase (GAD).
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  • Osteoarthritis affects nearly 27 million people in the US, accounting for 25% of visits to PCPs, and half of all NSAID prescriptions.
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  • Patients who undergo knee arthroplasty are at an increased risk of clinically important weight gain following surgery. http://bit.ly/106lCIE
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  • The major long-term toxicity of hydroxychloroquine use is the development of macular changes and loss of color vision.
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  • Pain and/or weakness with isometric testing of shoulder internal rotation suggest pathology in the subscapularis rotator cuff tendon
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  • Never initiate xanthine inhibitor therapy (allopurinol) during an acute gout attack. It can exacerbate and prolong the flare.
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  • Adhesive capsulitis (shoulder) is characterized by restricted range of motion (active AND passive) and nocturnal pain.
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  • Methotrexate competitively inhibits dihydrofolate reductase (DHFR), an enzyme that participates in the tetrahydrofolate synthesis.
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  • Adult Henoch Schönlein Purpura (HSP) patients generally have less abdominal pain and fever, and more joint symptoms and renal involvement.
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  • SLE patients with subacute cutaneous lupus erythematosus (SCLE) generally have mild disease with a low incidence of nephritis & arthritis.
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  • In diffuse idiopathic skeletal hyperostosis (DISH), the anatomical location of ossification occurs along the anterior longitudinal ligament
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  • Overgrowth causing limb length inequality is the second most frequent complication of oligoarticular JIA (uveitis is the most common).
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  • An isolated low DLco (on PFTs) in a patient with scleroderma (especially CREST) suggests pulmonary hypertension.
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  • Iliotibial band syndrome is a common injury in long-distance runners that usually develops with over-training and after vigorous running.
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  • De Quervain's tenosynovitis refers to tenosynovitis of the abductor pollicis longus and extensor pollicis brevis tendons.
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  • Finkelstein's test is used to diagnose DeQuervain's tenosynovitis. Grasp the thumb and the hand is ulnar deviated sharply to test for pain.
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  • Abatacept is a fusion protein (CTLA-4 Ig) which inhibits the costimulation of T cells by preventing binding of CD28 (T cell) and B7 (APC).
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  • Patients with HCV can have systemic vasculitis manifestations of polyarteritis nodosa type or mixed cryoglobulinemia type.
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  • Posterior tibial nerve compression (tarsal tunnel syndrome) presents with pain & numbness at the sole of the foot, distal foot, toes, & heel
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  • The WOMAC is a set of standardized questionnaires used to determine the overall level of disability in patients with OA of the knee and hip.
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  • Procainamide is associated with the highest incidence of drug-induced lupus of any available drug. Incidence with prolonged therapy is ~30%.
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  • 28% of SLE adult patients may carry an underlying primary immunodeficiency. #ACR2012
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  • The DAS28 scale is from 0 to 10. A score above 5.1 means high disease activity (RA) whereas a DAS28 below 3.2 indicates low disease activity
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  • Amongst the periodic febrile syndromes, responsiveness to colchicine is relatively specific to familial Mediterranean fever (FMF).
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  • Rheumatoid arthritis patients with anemia and a ferritin greater than 100ng/ml do not have iron deficiency anemia.
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  • Up to 10% of patients with biopsy proven GCA can have a normal ESR. Systemic manifestations are more common in those with high ESRs.
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  • Excessive overgrowth of craniofacial bones in craniometaphyseal dysplasia may result from a loss of function in ANKH gene product.
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  • All patients with rheumatoid arthritis needing pre-op clearance should have c-spine films because of the risk of atlantoaxial subluxation.
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  • Polymyalgia rheumatica (PMR) is almost exclusively a disease of adults over the age of 50. Prevalence increases progressively with age.
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  • Spondyloarthropathy occurs in ~ 20% of patients with inflammatory bowel disease. Occurs more often in Crohn’s than in ulcerative colitis.
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  • Varus alignment (bow-legs) increases the risk of knee OA 5-fold in obese patients. Valgus alignment (knock-kneed) is not as destructive.
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  • The first MTP is the most commonly involved joint in patients with gout. >50% of initial attacks and over time affects >90% of patients.
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  • Caplan's syndrome describes lung nodules only in patients with both RA and pneumoconiosis related to mining dust (coal, asbestos, silica).
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  • Urticarial lesions persisting for more than 48 hours are more likely to be related to an underlying vasculitis.
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  • Drug reaction w/ eosinophilia & systemic symptoms (DRESS) is notable for a long latency (2 – 8 wks) between drug exposure and disease onset
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  • Undifferentiated connective tissue diseases and “incomplete lupus” represent up to 10–20% of patients referred to rheumatologists.
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  • The vasculitis most commonly associated with hairy cell leukemia is polyarteritis nodosa (PAN).
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  • Four forms of vasculitis which commonly cause bruits: Takayasu’s arteritis, giant cell arteritis, Behcet’s disease, and Cogan’s syndrome.
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  • The most common arthritic manifestation of relapsing polychondritis is migratory tenosynovitis.
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  • CPPD (pseudogout) can be associated with a wide range of metabolic disorders including acromegaly, thyroid, and parathyroid conditions.
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  • Epiphysitis, presenting as a step-like erosion of the anterosuperior angle of the vertebra, is one of the earlier findings in spondylitis.
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  • In patients with RS3PE who don’t respond to low dose prednisone, consider the possibility of an underlying malignancy.
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  • The axial manifestations of spondyloarthopathies typically do not respond to methotrexate. TNFα antagonists are the treatment of choice.
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  • In women, the estimation of the upper limit of normal for the ESR is: ESR <= (age[yrs] + 10) / 2. For men: ESR <= age[yrs] / 2.
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  • Rheumatoid factor (RF) describes an antibody (IgM, IgG, or IgA) which targets the Fc portion of IgG. Together, they form immune complexes.
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  • The allopurinol hypersensitivity syndrome consists of rash, fever, hepatitis, eosinophilia, and renal failure. Mortality approaches 25%.
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  • Thromboangiitis obliterans (aka Buerger's disease) is strongly associated w/ smoking and the only effective therapy is smoking cessation.
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  • Life expectancy is shorter in patients with RA, & survival rates are comparable to Hodgkin's, diabetes, & 3-vessel coronary artery disease.
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  • Barefoot walking has been demonstrated to reduce the major force across the knee in patients with medial compartment knee OA.
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  • The shingles vaccine may be safe to give to SLE pts who have low disease activity and are on low doses of immunosuppressive meds. #ACR2012
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  • Legg-Calve-Perthes disease is avascular necrosis of the hip due to insufficient blood supply. Most commonly affects young, overweight boys.
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  • Alport's syndrome is a default in type IV collagen which effects the basement membrane.
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  • Milwaukee Shoulder (apatite-associated destructive arthritis) is the result of peri- or intraarticular deposition of hydroxyapatite crystals
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  • A major side effect of IVIg is aseptic meningitis, especially in patients with a history of migraines. Premedication with a triptan may help
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  • Whipple's disease is caused by Tropheryma whipplei. Characterized by insidious onset of weight loss, diarrhea, arthralgias, & abdominal pain
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  • In ankylosing spondylitis, inflammation has a predilection for fibrocartilaginous sites rich in aggrecans and type II collagen.
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  • In patients with Behçet's disease who present with severe headache and ocular pain, evaluate for cerebral venous thrombosis.
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  • Lupus patients with nephrotic syndrome are at increased risk for venous thrombosis, particularly deep vein and renal vein thrombosis.
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  • The most common sites for finding radiographic chondrocalcinosis are the knees, triangular fibrocartilage of the wrists, & pubic symphysis.
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  • Despite modern therapies, a lupus patient diagnosed at the age of 20 has a 1 in 6 chance of dying by the age of 35.
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  • Plasmacytoid dendritic cells are the major source of type I interferons associated with active systemic lupus erythematosus.
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  • In a patient with diffuse scleroderma, anti-RNA polymerase III is the antibody most associated with an increased risk for renal crisis
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  • “Realize that the most important biomarkers (in rheumatology) are the history and physical examination” – Steve Paget, HSS
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  • Celiac disease associated arthritis typically involves the lumbar spine, hips, knees, and shoulders and remits with gluten-free diet.
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  • An IgG1 autoantibody (NMO-IgG) that binds aquaporin 4 (AQP4) has been proposed as the primary autoimmune phenomenon in neuromyelitis optica.
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  • P-155 antibodies are directed against transcriptional intermediary factor & are most closely linked to malignancy associated dermatomyositis
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  • Children born to women w/ SLE have increased risk of congenital abnormalities, infections, and cardiac conduction abnormalities. #ACR2012
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  • Pes anserine bursitis is a common finding in patients and/or athletes who present with complaints of anterior knee pain.
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  • Th1 cells secrete IL-2 & interferon gamma (cell-mediated immunity). Th2 cells secrete IL-4, IL-5, IL-6, IL-10, & IL-13 (humoral immunity).
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  • BLyS is a cytokine expressed on B cells and has been shown to play an important role in B cell proliferation and differentiation.
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  • Type 1 autoimmune pancreatitis (AIM) is an organ manifestation of IgG4-related disease. Type 2 AIM appears to be a disease of its own.
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  • In psoriatic arthritis, a CRP >0.9 md/dl at diagnosis may predict an inadequate response to conventional DMARDS. #ACR2012
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  • Interdigital neuritis, or Morton’s neuroma, occurs most commonly in the web space between the third and fourth toes.
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  • Unlike most other diabetic complications affecting the hand, diabetic cheiroarthropathy is painless.
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  • CRP is usually normal in SLE flares and its elevation may reflect an active infection in a lupus patient with unclear clinical symptoms
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  • Familial Mediterranean fever (FMF) patients who are lactose intolerant may develop dose-limiting side effects of colchicine.
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  • Between 10% and 25% of patients with chronic ITP and a positive ANA develop SLE over time. Higher if AIHA is also present (Evans’syndrome).
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  • Livedo reticularis is strongly associated with the occurrence of arterial ischemic events in the antiphospholipid antibody syndrome.
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  • Acute calcific periarthritis is a common cause of podagra in young women (hydroxyapatite pseudopodgra). Gout would be much less likely.
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  • The pancreas was the first organ in which IgG4-related disease was identified, but it has now been described in virtually every organ system
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  • Screening for celiac sprue includes serologic testing with total IgA, IgA tissue transglutaminase or IgA endomysial antibody.
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  • One of the most common sites for erosions in patients with rheumatoid arthritis is the lateral aspect of the head of the 5th MTP.
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  • Hydroxyurea is the most commonly reported medication to induce drug-induced dermatomyositis (50-70% of case reports).
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  • Mixed cryoglobulinemia is a systemic vasculitis associated with hepatitis C. It is associated with purpura, arthralgia, and asthenia.
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  • HIDS patients (HyperImmuno-globulinemia D with periodic fever Syndrome) have a mutation in the MVK (mevalonate kinase) gene.
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  • Patients who have PM-Scl antibodies typically have an overlap syndrome of polymyositis or dermatomyositis with systemic sclerosis.
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  • "Moyamoya" is a Japanese word meaning obscure, or hazy, like a puff of smoke. Thus, the term is used to denote a vascular collateral network
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  • A prolonged PT in lupus is usually the result of a prothrombin (factor II) deficiency. These patients generally present with hemorrhage.
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  • Susac's syndrome is a microangiopathy characterized by the triad of encephalopathy, branch retinal artery occlusions and hearing loss.
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  • Neuropathic joints occur in 25% of patients with syringomyelia. The most common joint is the shoulder with about 80% occurrence.
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  • The incidence of ANA positivity with procainamide is ~90%. With hydralizine, ~50%, and with isoniazid, ~20%
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  • The active cyclophosphamide metabolite, phosphoramide mustard, forms DNA crosslinks at guanine positions and leads to cell death.
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  • Chilblain lupus is a cold-induced microvascular injury, initially resembling chilblains but eventually assumes the form of discoid lupus.
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  • A deficiency of either C1r or C1s is associated with SLE; these deficiencies generally have prominent renal and cutaneous manifestations.
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  • Crohn's disease articular manifestations tend to be asymmetric, migratory, and pauciarticular with large and small joint involvement.
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  • Activated T cells express IL-2R, and engagement of IL-2 results in enhanced T-cell proliferation.
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  • Mycoplasma hominis as an etiologic agent for septic arthritis in patients who have undergone genitourinary manipulation.
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  • Erosive osteoarthritis (EOA) is an aggressive subset of OA. The classic radiographic findings include “gull-wing” & “saw-tooth” deformities.
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  • Those who develop Raynaud’s phenomenon later in life (age >40) are more apt to have secondary Raynaud’s phenomenon.
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  • Interleukin 6 (IL-6) is a pro-inflammatory cytokine and one of the most important mediators of fever and of the acute phase response.
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  • Young children with oligoarticular onset, ANA positive, JIA should be screened every three to four months for uveitis.
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  • In Sjogren's, presence of subpleural honeycombing is suggestive of usual interstitial pneumonitis (UIP), which portends the worst prognosis
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  • IV drug users are susceptible to septic arthritis with unusual organisms (gram negatives) and in atypical axial sites (sternoclavicular).
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  • The prevalence of carpal tunnel syndrome is increased in the third trimester of pregnancy and it generally goes away after pregnancy.
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  • Up to one-third of lupus patients have one or more additional autoimmune diseases such as Sjogren's or Hashimoto's thyroiditis.
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  • A shorter disease duration and younger age are predictors of a major clinical response to TNF blockers in active ankylosing spondylitis
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  • Cellcept (MMF) inhibits inosine monophosphate dehydrogenase, which is a critical enzyme for the for the de-novo synthesis of guanosine.
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  • Eosinophilia-myalgia syndrome is characterized by pruritus, cutaneous lesions, sclerodermoid changes, arthralgias, myalgias and eosinophilia
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  • Periodontal disease is associated with rheumatoid arthritis but its severity is not correlated with RA disease activity. #ACR2012
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  • GCA accounts for 16% of cases of fever of unknown origin (FUO) in patients over 65 years old (but <2% of all cases of FUO).
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  • Patients with earlier onset SLE are more likely to have renal and neurologic involvement. #ACR2012 #lupus
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  • Carpal tunnel syndrome is the most common compression neuropathy. Symptoms include tingling and numbness in digits 1-3 and thenar atrophy.
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  • Hypertrophic lupus erythematosus is a form of discoid lupus characterized by verrucous hyperkeratotic lesions.
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  • MRL/lrp mice (lupus prone) carry a mutation in the Fas gene (affects cellular apoptosis). They develop anti-dsDNA, nephritis, & synovitis.
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  • Moyamoya disease is a noninflammatory vasculopathy and notable for stenosis or occlusion of the arteries around the circle of Willis.
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  • Pleural effusions in RA are exudates, with high protein and LDH levels & very low glucose. In contrast to empyemas, lymphocytes predominate.
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  • Weber-Christian disease (relapsing febrile nodular panniculitis) is an inflammatory infiltration of subcutaneous adipose tissue.
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  • In patients with scleroderma and abnormal esophageal manometry, almost all will also have abnormal anorectal motility.
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  • Osgood–Schlatter syndrome (tibial tubercle apophyseal traction injury) is an irritation of the patellar ligament at the tibial tuberosity
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  • Pseudogout is associated with hypoparathyroidism, hemochromatosis, hypomagnesemia, hypophosphatasia and hypothydroidism.
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  • The incidence of chondrocalcinosis increases with age, and over 30% of persons over 75 have chondrocalcinosis on the knees.
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  • IL-12 is a strong driver of Th1 cell differentiation. Th1 cells are defined by the production of the cytokine interferon-gamma
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  • The major cause of malabsorption in scleroderma is intestinal stasis w/ bacterial overgrowth. Patients are commonly managed with antibiotics
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  • Pigmented villonodular synovitis is a benign neoplasm that typically presents as an intra-articular tumor. Bloody effusions are common.
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  • Lofgren’s syndrome is a form of sarcoidosis & includes the clinical triad of hilar lymphadenopathy, acute polyarthritis, & erythema nodosum.
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  • The most common types of soft tissue rheumatism are subacromial bursitis, epicondylitis, trochanteric bursitis, and fibromyalgia.
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  • B Lymphocye Stimulator (BLyS) levels are higher in SLE patients who present at a younger age and predict damage accumulation. #ACR2012
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  • Nephrogenic systemic fibrosis (NSF) is seen exclusively in patients with renal insufficiency who have undergone a gadolinium (contrast) MRI
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  • Posterior interosseous neuropathy is a cause of lateral elbow pain and hand weakness and can be a complication of rheumatoid arthritis.
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  • Elevations in ESR due to advanced age or sex can be calculated according to the following equation: ESR(mm/hr) < age (+10 for women) / 2
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  • Diffuse infiltrative lymphocytosis syndrome (DILS) is a disorder that mimics Sjogren's and is seen in HIV patients.
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  • Polyarteritis nodosa (PAN) can be associated with hepatitis B. Classic PAN usually manifests within the first 6 mo of hepatitis B infection
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  • When PMR-like symptoms do not respond appropriately to prednisone, other diagnoses should be considered, like PMR associated w/ malignancy.
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  • The presence of HLA-B5 is associated with Behçet's disease, ulcerative colitis, and polycystic kidney disease.
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  • In GCA, diagnostic histopathologic findings on temporal artery biopsy can be seen even 2 weeks after the institution of steroid therapy.
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  • Erythema nodosum and peripheral arthritis are both more common in Crohn's disease than ulcerative colitis.
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  • Flexor hallucis longus tendinopathy, commonly known as dancer's tendinopathy, commonly is found among dancers, especially ballet dancers.
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  • Congenital heart block, due to anti-Ro and anti-La, is most often identified between 18 and 30 weeks gestation.
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  • The anti-synthetase syndrome is marked by myositis, Raynaud’s, ILD, & mechanic’s hands. Most often associated with anti-Jo-1 antibodies.
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  • Intrauterine fetal heart block occurs in 2% of pregnant women with anti-Ro/SSA antibodies. Recurrence rate is 16% for subsequent pregnancies
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  • The arthritis of acute rheumatic fever is usually migratory and affects predominantly the large joints.
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  • Septic joint infections are divided into gonococcal and non-gonococcal. Common causes of non-gonococcal are staph, strep, and E. coli.
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  • Wegener's granulomatosus is believed to be two or three times more common than MPA in western countries. This ratio is inverted in Japan.
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  • In psoriatic arthritis, nearly 15% of patients will develop psoriasis AFTER the onset of arthritis.
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  • Plaquenil can theoretically reduce the analgesic effect of both codeine and tramadol due to cytochrome P450 2D6 inhibition.
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  • Pulmonary function tests in interstitial lung disease (ILD) typically show a normal or elevated FEV1/FVC ratio and a decreased DLCO.
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  • Th1 cells help defend against intracellular pathogens like mycobacteria. Th17 cells help defend against extracellular bacteria and fungi
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  • Lupus nephritis occurs twice as frequently in African Americans with SLE than compared to Caucasians with SLE.
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  • Tocilizumab is a humanized monoclonal antibody against the interleukin-6 receptor. It is approved for the treatment of rheumatoid arthritis.
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  • Synovial fluid crystals with a “Maltese cross” appearance on light microscopy indicate lipid drops & are suggestive of subchondral fracture.
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  • Since probenecid increased urinary calcium excretion in gouty patients, it should be avoided in patients with prior nephrolithiasis.
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  • Osteochondritis dissecans is a result of chronic microtrauma and represents a form of avascular necrosis that is small and focal.
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  • The majority of African-Americans with rheumatoid arthritis do not carry the shared epitope in their DR genes (in contrast to Caucasians).
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  • Dural ectasia is a common cause of low back pain and radicular pain in patients with Marfan syndrome.
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  • Anti-DNA cross reacting w/ brainstem neuronal receptors induce apoptosis & cause preferential loss of female fetuses in murine SLE. #ACR2012
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  • Survival in SLE has improved significantly, but patients still have 3-5 times increased mortality compared to the general population.
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  • There are currently 171 known types of arthritis, from acromegalic arthropathy to yersinia arthritis.
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  • Patients with RS3PE (remitting seronegative symmetrical synovitis with pitting edema) have sudden onset polyarthritis and are RF negative.
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  • Acute calcineurin inhibitor nephrotoxicity causes vasoconstriction of the afferent and efferent glomerular arterioles and a reduction in GFR
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  • Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory spondyloarthropathy (aka Forestier's disease & ankylosing hyperostosis)
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  • Great apes, dalmatian dogs, & humans are the only mammals that lack a functional uricase gene and, thus, are the only mammals who get gout.
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  • There are approximately 640 muscles in the human body. Muscle constitutes up to 40% of the adult body mass.
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  • All patients with newly diagnosed reactive arthritis should have an HIV test. Reactive arthritis develops in 75% of HIV patients w/ HLA-B27.
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  • PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis & adenitis) is seen in children. Fevers occurs periodically every 3–5 weeks
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  • In obese patients with knee OA, losing even just one pound results in a 4-pound reduction in knee-joint load for each step.
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  • The calcineurin inhibitors (tacrolimus, cyclosporine) are immunosuppressants which reduce interleukin-2 (IL-2) production by T-cells.
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  • Osteopetrosis is caused by an osteoclast proton pump deficiency resulting in a failure of bone resorption while its formation persists.
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  • Usual interstitial pneumonitis (UIP) is more commonly seen in patients with Sjogren syndrome secondary to RA and SLE rather than primary SS
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  • I patients with lupus, the presence of an anticardiolipin antibody can cause a false positive test for syphilis (RPR).
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  • Lupus erythematosus tumidus (LE tumidus) is characterized by smooth, erythematous plaques on sun-exposed areas without surface changes.
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  • Patients with primary Sjögren’s syndrome and hypocomplementemia, particularly C4, are at increased risk for the development of lymphoma.
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  • Celiac disease is associated with arthritis in ~9% of patients. Typically nonerosive and usually responds to a gluten free diet.
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  • Patients with IBD (Crohn’s and UC) spondyloarthritis tend to develop posterior uveitis more commonly than other spondyloarthropathies
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  • Serum IgA antiendomysial and anti-tissue transglutaminase antibodies are highly specific and sensitive for celiac disease.
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  • CD40L (activated T-cells) binding with CD40 (B cells) induces immunoglobulin class switching from IgM to IgG secretory responses in B cells.
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  • The target uric acid level for a patient with tophaceous gout is <4.0 mg/dL (compared to non-tophaceous gout where the target is <6.0 mg/dL)
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  • Vascular Ehlers Danlos (EDS type IV) patients demonstrate abnormalities in type III procollagen (found in hollow organs and vessels).
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  • Neuropathic arthropathy of hands & wrists due to cervical syringomyelia can result in articular deformities resembling rheumatoid arthritis
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  • Probenecid is a uricosuric agent used for urate lowering therapy but it is generally not considered effective in tophaceous gout.
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  • B Lymphocyte Stimulator (BLyS) binds to 3 different receptors with variable affinity. BAFF-R more than BCMA more than TACI.
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  • SAPHO syndrome is an inflammatory bone disorder assoc w/ skin changes. It stands for Synovitis, Acne, Pustulosis, Hyperostosis, & Osteitis.
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  • The first animal model of systemic lupus erythematosus was the F1 hybrid New Zealand Black/New Zealand White mouse.
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  • IgG4-related disease is a fibroinflammatory condition characterized by formation IgG4+ plasma cells, fibrosis, a swift response to steroids.
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  • Belimumab does reduce the number of circulating B cells, but less significantly and durably than anti-CD20 monoclonal antibodies.
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  • When evaluating a patient for Sjögren's, ask about dental health as poor dentition is associated with inadequate salivary production.
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  • Osteoid osteoma is a solitary benign lesion of bone usually occurring in a long bone cortex. Presents in 2nd or 3rd decade of life.
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  • Rheumatoid vasculitis in more common in patients who have had severe, destructive RA but whose joints are no longer active (burnt out).
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  • Foreign bodies such as thorns can lead to chronic tenosynovitis, bursitis & aseptic monoarticular synovitis in relation to the puncture site
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  • Although controversial, the frequency of autoimmune thyroiditis (Hashimoto's) is reportedly increased in those with Sjögren's syndrome.
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  • The prevalence of ankylosing spondylitis ranges between 0.1% and 1%, with a male predominance of 2-3:1.
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  • A febrile patient with HIV and a recent onset of thigh pain and swelling most likely has pyomyositis.
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  • The sensitivity and specificity of anti-CCP reactivity for the diagnosis of rheumatoid arthritis is 74.0% and 94.5%, respectively.
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  • Cubital tunnel syndrome is caused by entrapment or irritation of the ulnar nerve in the groove behind the medial epicondyle.
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  • Movement disorders seen in CNS lupus (tremors, chorea, and extrapyramidal syndromes) may improve with management of the underlying disease.
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  • Muckle-Wells syndrome is caused by a defect in the CIAS1 gene. Patients have fevers, sensorineural deafness, recurrent hives, & amyloidosis
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  • Complex regional pain syndrome (CRPS) Type I, (formerly reflex sympathetic dystrophy (RSD)), does not have demonstrable nerve lesions.
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  • Gouty arthritis is associated with nodal OA, particularly in elderly women with renal failure, HTN, or CHF on long term diuretic therapy.
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  • Asians are more prone to Allopurinol hypersensitivity syndrome (aka DRESS) so consider starting at a lower initial dose.
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  • Mixed connective tissue disease (MCTD) (aka Sharp Syndrome) was first described in 1972 by Gordon C. Sharp and colleagues.
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  • In relapsing polychondritis, an immune response against collagens II, IX, and XI has been demonstrated for many patients.
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  • The development of mononeuritis multiplex in the absence of diabetes or compression injuries strongly suggests the presence of vasculitis.
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  • Chilblain lupus is a rare variant of discoid lupus. Lesions are tender, purplish nodules often affecting the fingers, ears, calves, & heels
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  • The most serious complication of pauciarticular JIA is uveitis or iridocyclitis (20% of JIA). ANA positive patients are at greatest risk.
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  • In most cases of primary angiitis of the CNS, abnormal CSF will be seen, including increased WBCs or an elevated total protein or both.
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  • Risk factors for the development of mesenteric vasculitis in lupus patients (lupus enteritis) include peripheral vasculitis and CNS lupus.
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  • The pericarditis of SLE is often painful whereas pericarditis in scleroderma and rheumatoid arthritis is generally painless.
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  • McArdle’s disease is the most common glycogen storage disease. Most patients have an elevated CK level and have myopathic changes on EMG.
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  • Cogan's syndrome hallmarks include interstitial keratitis and vestibuloauditory dysfunction. It is most commonly seen in young adults.
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There are currently 329 rheumatology pearls in the database.
The lastest pearl was added March 19, 2014
Download a copy of my poster presented at the 2011 ACR conference here!

Welcome to Rheumatology Pearls

This site is a rather simple educational exercise in the distribution of medical "pearls of wisdom" about rheumatology. There are currently 329 pearls in the database which cover a variety of rheumatologic topics including clinical diagnosis, laboratory tests, genetics, basic science and medications. The pearls are each 140 characters or less and thus are "tweetable" and allow for experimentation in micro-blogging and medical education. There is twitter feed associated with this website @RheumPearls.

The pearls themselves are written by Dr. Christopher Collins M.D., a Rheumatologist at the Washington Hospital Center in Washington DC, and new pearls are added frequently. If you notice an error with one of the pearls, please let us know. Additionally, if you have a rheumatology pearl you would like to submit, send it to us here.