Rheumatology Pearls

The pearls are grouped by subject. Jump to...

Rheumatoid Arthritis
Return to top
All patients with rheumatoid arthritis needing pre-op clearance should have c-spine films because of the risk of atlantoaxial subluxation.
Life expectancy is shorter in patients with RA, & survival rates are comparable to Hodgkin's, diabetes, & 3-vessel coronary artery disease.
One of the most common sites for erosions in patients with rheumatoid arthritis is the lateral aspect of the head of the 5th MTP.
The DAS28 is an index of RA disease activity. Calculated using a 28 tender & swollen joint count, ESR (or CRP), & patient global health VAS.
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
Young children with oligoarticular onset, ANA positive, JIA should be screened every three to four months for uveitis.
Posterior interosseous neuropathy is a cause of lateral elbow pain and hand weakness and can be a complication of rheumatoid arthritis.
Pleural effusions in RA are exudates, with high protein and LDH levels & very low glucose. In contrast to empyemas, lymphocytes predominate.
Pericarditis often presents early in rheumatoid vasculitis. Its development should trigger an evaluation for other hallmarks of vasculitis.
Rheumatoid vasculitis in more common in patients who have had severe, destructive RA but whose joints are no longer active (burnt out).
Rheumatoid vasculitis overlaps substantially with polyarteritis nodosa and tends to affect the same types of organs.
Felty’s syndrome is characterized by rheumatoid arthritis, splenomegaly and leukopenia with associated recurrent infections.
Rheumatoid arthritis is currently one of the most frequent causes of amyloidosis of the AA type, however the prevalence is declining.
Rheumatoid arthritis can be seen in patients with T-cell large granular lymphocyte leukemia (T-LGL). Presentation is similar to Felty's.
Palindromic rheumatism - episodic inflammation in usually 2 to 3 joints, large joints commonly. There is no joint damage after attacks.
Periodontal disease is associated with rheumatoid arthritis but its severity is not correlated with RA disease activity. #ACR2012
Overgrowth causing limb length inequality is the second most frequent complication of oligoarticular JIA (uveitis is the most common).
When considering intra-articular injections for polyarthritis in a JIA patient, triamcinolone hexacetonide is the preferred corticosteroid.
General rheumatology
Return to top
There are approximately 640 muscles in the human body. Muscle constitutes up to 40% of the adult body mass.
There are currently 171 known types of arthritis, from acromegalic arthropathy to yersinia arthritis.
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
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.
In acute gonococcal septic arthritis, GC is rarely seen on gram stain or by culture. Furthermore, low WBC counts on synovial fluid do occur.
Septic joint infections are divided into gonococcal and non-gonococcal. Common causes of non-gonococcal are staph, strep, and E. coli.
Postglucocorticoid hypopigmentation of the skin can be avoided by the injection of air following the medication.
Superior migration of the humeral head detected by plain radiography indicates a significant rotator cuff tear.
Undifferentiated connective tissue diseases and “incomplete lupus” represent up to 10–20% of patients referred to rheumatologists.
De Quervain's tenosynovitis refers to tenosynovitis of the abductor pollicis longus and extensor pollicis brevis tendons.
Trigger finger (aka stenosing flexor tenosynovitis) is noninfectious inflammation of the flexor tendon sheath of the finger (or thumb).
Dupuytren's contracture is progressive fibrosis of the palmar fascia resulting in contractures of one or more fingers at the MCP joints.
All patients with fibromyalgia should be asked about symptoms of sleep apnea. Physical therapy and amitriptyline won’t work unless corrected
Rule out vitamin D insufficiency/ deficiency in patients losing bone mineral density while receiving therapy for osteoporosis.
Post-steroid injection flares are likely due to crystallization of the steroid within the joint. Pain usually resolves within 1-2 days.
Pain and/or weakness with isometric testing of shoulder internal rotation suggest pathology in the subscapularis rotator cuff tendon
Approximately 10-15% of arthroplasties fail, the most common cause for which is osteolysis (inflammation initiated by arthroplasty debris)
“Realize that the most important biomarkers (in rheumatology) are the history and physical examination” – Steve Paget, HSS
Return to top
The presence of HLA-B5 is associated with Behçet's disease, ulcerative colitis, and polycystic kidney disease.
HIDS patients (HyperImmuno-globulinemia D with periodic fever Syndrome) have a mutation in the MVK (mevalonate kinase) gene.
TRAPS patients (TNF receptor-assoc. periodic syndrome) have a mutation in the TNFRSF1A (TNF receptor) gene.
Familial CPPD is associated with a gain of function of the ANKH gene product, leading to increased extracellular pyrophosphate.
NOMID (neonatal onset multisystem inflammatory disease) can result from a mutation in the CIAS1 gene, which helps control inflammation.
In lupus patients, IRF5, IRAK1, and STAT4 genes are important for dendritic cell type I interferon production.
Excessive overgrowth of craniofacial bones in craniometaphyseal dysplasia may result from a loss of function in ANKH gene product.
Two alleles, DRB1*0401 and DRB1*0404, primarily account for the DR4 association with rheumatoid arthritis in Caucasians.
The majority of African-Americans with rheumatoid arthritis do not carry the shared epitope in their DR genes (in contrast to Caucasians).
Marfan syndrome results from mutations in the fibrillin-1 (FBN1) gene on chromosome 15, which encodes for the glycoprotein fibrillin.
Basic science
Return to top
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).
MRL/lrp mice (lupus prone) carry a mutation in the Fas gene (affects cellular apoptosis). They develop anti-dsDNA, nephritis, & synovitis.
Vascular Ehlers Danlos (EDS type IV) patients demonstrate abnormalities in type III procollagen (found in hollow organs and vessels).
Interleukin 6 (IL-6) is a pro-inflammatory cytokine and one of the most important mediators of fever and of the acute phase response.
Plasmacytoid dendritic cells are the major source of type I interferons associated with active systemic lupus erythematosus.
The first animal model of systemic lupus erythematosus was the F1 hybrid New Zealand Black/New Zealand White mouse.
ALPS (autoimmune lymphoproliferative syndrome) is a disorder of the Fas-Fas ligand pathway that leads to a defect in lymphocyte apoptosis.
CD40L (activated T-cells) binding with CD40 (B cells) induces immunoglobulin class switching from IgM to IgG secretory responses in B cells.
Activated T cells express IL-2R, and engagement of IL-2 results in enhanced T-cell proliferation.
A deficiency of either C1r or C1s is associated with SLE; these deficiencies generally have prominent renal and cutaneous manifestations.
In relapsing polychondritis, an immune response against collagens II, IX, and XI has been demonstrated for many patients.
BLyS is a cytokine expressed on B cells and has been shown to play an important role in B cell proliferation and differentiation.
B Lymphocyte Stimulator (BLyS) binds to 3 different receptors with variable affinity. BAFF-R more than BCMA more than TACI.
An IgG1 autoantibody (NMO-IgG) that binds aquaporin 4 (AQP4) has been proposed as the primary autoimmune phenomenon in neuromyelitis optica.
IL-12 is a strong driver of Th1 cell differentiation. Th1 cells are defined by the production of the cytokine interferon-gamma
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
Th1 cells help defend against intracellular pathogens like mycobacteria. Th17 cells help defend against extracellular bacteria and fungi
Crystal arthropathies
Return to top
The first MTP is the most commonly involved joint in patients with gout. >50% of initial attacks and over time affects >90% of patients.
The most common sites for finding radiographic chondrocalcinosis are the knees, triangular fibrocartilage of the wrists, & pubic symphysis.
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)
Never initiate xanthine inhibitor therapy (allopurinol) during an acute gout attack. It can exacerbate and prolong the flare.
Gouty arthritis is associated with nodal OA, particularly in elderly women with renal failure, HTN, or CHF on long term diuretic therapy.
Milwaukee Shoulder (apatite-associated destructive arthritis) is the result of peri- or intraarticular deposition of hydroxyapatite crystals
Since probenecid increased urinary calcium excretion in gouty patients, it should be avoided in patients with prior nephrolithiasis.
Great apes, dalmatian dogs, & humans are the only mammals that lack a functional uricase gene and, thus, are the only mammals who get gout.
Synovial fluid crystals with a “Maltese cross” appearance on light microscopy indicate lipid drops & are suggestive of subchondral fracture.
The incidence of chondrocalcinosis increases with age, and over 30% of persons over 75 have chondrocalcinosis on the knees.
Pseudogout is associated with hypoparathyroidism, hemochromatosis, hypomagnesemia, hypophosphatasia and hypothydroidism.
Indications for urate lowering therapy include tophaceous gout, erosive changes on xray, nephrolithiasis, & 2 or more gout attacks per year.
Acute calcific periarthritis is a common cause of podagra in young women (hydroxyapatite pseudopodgra). Gout would be much less likely.
Isolated patello-femoral compartmental degenerative changes in the knee is an important indicator of CPPD. (submitted pearl - thanks!)
Up to 15% of patients with chondrocalcinosis will be found to have primary hyperparathyroidism
Over 50% of patients with long-standing primary hyperparathyroidism will have radiographic evidence of chondrocalcinosis
Systemic lupus erythematosus
Return to top
Lupus patients should avoid sulfa-containing antibiotics because of a high incidence of skin rash & other side effects including lupus flare
Lupus anticoagulant is an immunoglobulin that interacts with platelet membrane phospholipids, increasing adhesion & aggregation of platelets
Class IV lupus nephritis (diffuse proliferative) is the renal lesion associated with the highest morbidity and mortality for lupus patients.
Chilblain lupus is a rare variant of discoid lupus. Lesions are tender, purplish nodules often affecting the fingers, ears, calves, & heels
Intrauterine fetal heart block occurs in 2% of pregnant women with anti-Ro/SSA antibodies. Recurrence rate is 16% for subsequent pregnancies
Discoid lesions in children and adolescents are likely secondary to SLE, not to isolated discoid lupus.
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).
A prolonged PT in lupus is usually the result of a prothrombin (factor II) deficiency. These patients generally present with hemorrhage.
Hand deformity in SLE (Jaccoud’s arthropathy) results from ligamentous laxity rather than the destructive synovial pannus of RA.
Patients with “rhupus” have an overlap syndrome with clinical and serologic signs of both SLE and RA, including radiographic erosions.
Up to one-third of lupus patients have one or more additional autoimmune diseases such as Sjogren's or Hashimoto's thyroiditis.
The malar rash of SLE is not transient. Because inflammation takes time to resolve, lupus rashes do not resolve within hours.
Risk factors for the development of mesenteric vasculitis in lupus patients (lupus enteritis) include peripheral vasculitis and CNS lupus.
Survival in SLE has improved significantly, but patients still have 3-5 times increased mortality compared to the general population.
Congenital heart block, due to anti-Ro and anti-La, is most often identified between 18 and 30 weeks gestation.
The pericarditis of SLE is often painful whereas pericarditis in scleroderma and rheumatoid arthritis is generally painless.
Movement disorders seen in CNS lupus (tremors, chorea, and extrapyramidal syndromes) may improve with management of the underlying disease.
SLE patients with subacute cutaneous lupus erythematosus (SCLE) generally have mild disease with a low incidence of nephritis & arthritis.
Children with SLE often require higher doses prednisone than their adult counterparts because of rapid drug metabolism (2 mg/kg vs 1 mg/kg).
I patients with lupus, the presence of an anticardiolipin antibody can cause a false positive test for syphilis (RPR).
Chilblain lupus is a cold-induced microvascular injury, initially resembling chilblains but eventually assumes the form of discoid lupus.
Hypertrophic lupus erythematosus is a form of discoid lupus characterized by verrucous hyperkeratotic lesions.
Lupus nephritis occurs twice as frequently in African Americans with SLE than compared to Caucasians with SLE.
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.
Approximately 33% of lupus patients stop working within 4 years of their diagnosis due to disability.
Lupus patients with nephrotic syndrome are at increased risk for venous thrombosis, particularly deep vein and renal vein thrombosis.
Sudden flank pain and worsening proteinuria in a lupus patient with known glomerulonephritis should be assessed for renal vein thrombosis.
Independent predictors of disease activity in pts w/ lupus include age, renal activity, immunosuppressant use and pre-existing organ damage
B Lymphocye Stimulator (BLyS) levels are higher in SLE patients who present at a younger age and predict damage accumulation. #ACR2012
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
Compared to the general population, there is a substantial increase in the male-to-female ratio in children born to women with SLE. #ACR2012
Anti-DNA cross reacting w/ brainstem neuronal receptors induce apoptosis & cause preferential loss of female fetuses in murine SLE. #ACR2012
28% of SLE adult patients may carry an underlying primary immunodeficiency. #ACR2012
Children born to women w/ SLE have increased risk of congenital abnormalities, infections, and cardiac conduction abnormalities. #ACR2012
The risk of lupus panniculitis is associated with discoid lupus, leg ulcers, serositis, and myositis, but not proteinuria. #ACR2012
Patients with earlier onset SLE are more likely to have renal and neurologic involvement. #ACR2012 #lupus
Lupus erythematosus tumidus (LE tumidus) is characterized by smooth, erythematous plaques on sun-exposed areas without surface changes.
PML should be considered in lupus patients with progressive neurologic deficits especially if immunosuppression is ineffective.
CRP is usually normal in SLE flares and its elevation may reflect an active infection in a lupus patient with unclear clinical symptoms
In pregnant SLE patients who are flaring, starting azathioprine may not be all that effective. Better when started before. Pred still best.
Lupus anticoagulant has the most significant odds ratio for the occurrence of CVA, not ACA or anti-prothrombin.
Soft tissue rheumatism
Return to top
Lateral epicondylitis is also known as tennis elbow. Medial epicondylitis is also known as golfer's elbow.
The most common types of soft tissue rheumatism are subacromial bursitis, epicondylitis, trochanteric bursitis, and fibromyalgia.
Adhesive capsulitis (shoulder) is characterized by restricted range of motion (active AND passive) and nocturnal pain.
Carpal tunnel syndrome is the most common compression neuropathy. Symptoms include tingling and numbness in digits 1-3 and thenar atrophy.
Finkelstein's test is used to diagnose DeQuervain's tenosynovitis. Grasp the thumb and the hand is ulnar deviated sharply to test for pain.
Paresthesia (burning) or hypesthesia (numbness and tingling) over the upper outer thigh is the classic presentation of meralgia paresthetica
The prevalence of carpal tunnel syndrome is increased in the third trimester of pregnancy and it generally goes away after pregnancy.
Iliotibial band syndrome is a common injury in long-distance runners that usually develops with over-training and after vigorous running.
Posterior tibial nerve compression (tarsal tunnel syndrome) presents with pain & numbness at the sole of the foot, distal foot, toes, & heel
Interdigital neuritis, or Morton’s neuroma, occurs most commonly in the web space between the third and fourth toes.
Anserine bursitis is a major cause of knee pain in some patients with osteoarthritis of the knee.
Pronator teres syndrome results from median nerve entrapment at the elbow - frequently accompanied by weakness of the index & middle fingers
Cubital tunnel syndrome is caused by entrapment or irritation of the ulnar nerve in the groove behind the medial epicondyle.
Pes anserine bursitis is a common finding in patients and/or athletes who present with complaints of anterior knee pain.
In any patient w/ patellofemoral disease, rule out hypermobility & pes planus. If present, shoe orthotics are a necessary part of therapy.
Flexor hallucis longus tendinopathy, commonly known as dancer's tendinopathy, commonly is found among dancers, especially ballet dancers.
Osgood–Schlatter syndrome (tibial tubercle apophyseal traction injury) is an irritation of the patellar ligament at the tibial tuberosity
Dural ectasia is a common cause of low back pain and radicular pain in patients with Marfan syndrome.
Return to top
In Wegener's granulomatosus, a lung biopsy is the most likely site to detect the diagnostic triad of vasculitis, granulomata, and necrosis.
Thromboangiitis obliterans (aka Buerger's disease) is strongly associated w/ smoking and the only effective therapy is smoking cessation.
The ANCA-associated vasculitidies (Wegener's, Churg Strauss, & MPA) are all associated with a pauci-immune glomerular nephritis.
Mixed cryoglobulinemia is a systemic vasculitis associated with hepatitis C. It is associated with purpura, arthralgia, and asthenia.
Patients with ANCA negative Churg-Strauss syndrome are more likely to have cardiac and parenchymal lung disease.
When PMR-like symptoms do not respond appropriately to prednisone, other diagnoses should be considered, like PMR associated w/ malignancy.
Urticarial lesions persisting for more than 48 hours are more likely to be related to an underlying vasculitis.
Wegener's granulomatosus is believed to be two or three times more common than MPA in western countries. This ratio is inverted in Japan.
About 10% of patients with giant cell arteritis GCA have upper respiratory symptoms including a sore throat and nonproductive cough.
PMR occurs in about 50% of patients with GCA, while approximately 15 to 30% of patients with PMR eventually develop GCA.
When getting a skin biopsy for Henoch Schönlein Purpura (HSP), make sure to send a sample for immunofluorescence looking for IgA deposits.
In children, Henoch Schönlein Purpura (HSP) is usually benign and self-limiting, however in adults, can be severe with worse outcomes.
Adult Henoch Schönlein Purpura (HSP) patients generally have less abdominal pain and fever, and more joint symptoms and renal involvement.
About 7% of patients with polyarteritis nodosa (PAN) have hepatitis B virus (HBV), but fewer than 1% of patients with HBV develop PAN.
GI involvement occurs in ~50% of patients with polyarteritis nodosa (PAN) (with gallbladder and small bowel the most frequently involved).
The development of mononeuritis multiplex in the absence of diabetes or compression injuries strongly suggests the presence of vasculitis.
In GCA, diagnostic histopathologic findings on temporal artery biopsy can be seen even 2 weeks after the institution of steroid therapy.
New unexplained pain located above the neck in a patient over 60 years old should suggest the possibility of giant cell arteritis.
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).
Up to 10% of patients with biopsy proven GCA can have a normal ESR. Systemic manifestations are more common in those with high ESRs.
Diplopia caused by ischemia of extraocular muscles, cranial nerves, or the brainstem may be a feature of GCA in up to 15% of patients.
Most polymyalgia rheumatica (PMR) patients demonstrate striking improvement in their symptoms with 24 to 48 hours of beginning steroids.
If a patient with PMR consistently requires > 20 mg of prednisone a day to control the disease symptoms, the diagnosis is probably wrong.
Four forms of vasculitis which commonly cause bruits: Takayasu’s arteritis, giant cell arteritis, Behcet’s disease, and Cogan’s syndrome.
Moyamoya disease is a noninflammatory vasculopathy and notable for stenosis or occlusion of the arteries around the circle of Willis.
"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
In most cases of primary angiitis of the CNS, abnormal CSF will be seen, including increased WBCs or an elevated total protein or both.
Polyarteritis nodosa (PAN) can be associated with hepatitis B. Classic PAN usually manifests within the first 6 mo of hepatitis B infection
In patients with Behçet's disease who present with severe headache and ocular pain, evaluate for cerebral venous thrombosis.
The most frequent ocular manifestation in patients with Cogan syndrome is interstitial keratitis. Tx is with steroids and immunosupprants
Patients with HCV can have systemic vasculitis manifestations of polyarteritis nodosa type or mixed cryoglobulinemia type.
The vasculitis most commonly associated with hairy cell leukemia is polyarteritis nodosa (PAN).
Return to top
Cellcept (MMF) inhibits inosine monophosphate dehydrogenase, which is a critical enzyme for the for the de-novo synthesis of guanosine.
Trimethoprim/sulfamethoxazole can enhance the cytotoxic effects of methotrexate because trimethoprim is an antifolate reductase inhibitor.
Methotrexate competitively inhibits dihydrofolate reductase (DHFR), an enzyme that participates in the tetrahydrofolate synthesis.
Leflunomide (rheumatoid arthritis DMARD) works by inhibiting dihydroorotate dehydrogenase (enzyme involved in de novo pyrimidine synthesis).
The active cyclophosphamide metabolite, phosphoramide mustard, forms DNA crosslinks at guanine positions and leads to cell death.
Denosumab is a monoclonal antibody targeted against RANK ligand and is FDA approved for the treatment of osteoporosis.
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).
The calcineurin inhibitors (tacrolimus, cyclosporine) are immunosuppressants which reduce interleukin-2 (IL-2) production by T-cells.
Tocilizumab is a humanized monoclonal antibody against the interleukin-6 receptor. It is approved for the treatment of rheumatoid arthritis.
There are currently 5 FDA approved anti-TNFα agents: infliximab, etanercept, adalimumab, golimumab, and certolizumab pegol.
Cochicine-induced axonal neuromyopathy most commonly occurs when renal dysfunction is present, but it is reversible not permanent.
Leflunomide is known to cause significant increases in systolic and diastolic blood pressures within 2–4 weeks of initiation.
Melanonychia, or nail hyperpigmentation, is a well-described reversible adverse effect of cyclophosphamide.
Leflunomide (pregnancy category X) is detectable in plasma up to 3 years after discontinuation. Cholestyramine is given to enhance clearance
The use of azathioprine & allopurinol together can lead to a severe drug–drug interaction. It is usually better not to use this combination.
Zidovudine induced myopathy causes myalgias, muscle tenderness, proximal muscle weakness, & muscle atrophy. CPK levels are elevated 10 fold.
The major long-term toxicity of hydroxychloroquine use is the development of macular changes and loss of color vision.
Belimumab is the first biologic therapy approved for the treatment of lupus. It is a monoclonal antibody which targets the cytokine BLyS.
Probenecid is a uricosuric agent used for urate lowering therapy but it is generally not considered effective in tophaceous gout.
Acetaminophen (Tylenol) potentiates the anticoagulant effect of coumadin so use caution with prescribing both.
Procainamide is associated with the highest incidence of drug-induced lupus of any available drug. Incidence with prolonged therapy is ~30%.
The incidence of ANA positivity with procainamide is ~90%. With hydralizine, ~50%, and with isoniazid, ~20%
Asians are more prone to Allopurinol hypersensitivity syndrome (aka DRESS) so consider starting at a lower initial dose.
Belimumab does reduce the number of circulating B cells, but less significantly and durably than anti-CD20 monoclonal antibodies.
The ARB (angiotensin receptor blocker) losartan has a uric acid-lowering effect.
A major side effect of IVIg is aseptic meningitis, especially in patients with a history of migraines. Premedication with a triptan may help
Acute calcineurin inhibitor nephrotoxicity causes vasoconstriction of the afferent and efferent glomerular arterioles and a reduction in GFR
Hydroxyurea is the most commonly reported medication to induce drug-induced dermatomyositis (50-70% of case reports).
Musculoskeletal side effects are seen in 40 to 60% of patients taking aromatase inhibitors like anastrozole
Drug reaction w/ eosinophilia & systemic symptoms (DRESS) is notable for a long latency (2 – 8 wks) between drug exposure and disease onset
Patients with DRESS syndrome often have a prolonged course with frequent relapses despite the discontinuation of the culprit drug
Plaquenil can theoretically reduce the analgesic effect of both codeine and tramadol due to cytochrome P450 2D6 inhibition.
Delayed-onset neutropenia is an increasingly recognized potential complication following rituximab infusion
Return to top
The 5 types of psoriatic arthritis are: symmetric, asymmetric, distal interphalangeal predominant, spondylitis, and arthritis mutilans.
All patients with newly diagnosed reactive arthritis should have an HIV test. Reactive arthritis develops in 75% of HIV patients w/ HLA-B27.
Spondyloarthropathy occurs in ~ 20% of patients with inflammatory bowel disease. Occurs more often in Crohn’s than in ulcerative colitis.
Ferguson views (plain radiograph) are useful for evaluation of the entire length of the sacroiliac joints symmetrically.
The axial manifestations of spondyloarthopathies typically do not respond to methotrexate. TNFα antagonists are the treatment of choice.
Epiphysitis, presenting as a step-like erosion of the anterosuperior angle of the vertebra, is one of the earlier findings in spondylitis.
Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory spondyloarthropathy (aka Forestier's disease & ankylosing hyperostosis)
The prevalence of ankylosing spondylitis ranges between 0.1% and 1%, with a male predominance of 2-3:1.
Reactive arthritis appears to be triggered by CD8+ T cells responding to peptides derived from bacteria which are bound to HLA-B27.
In ankylosing spondylitis, inflammation has a predilection for fibrocartilaginous sites rich in aggrecans and type II collagen.
In patients with psoriasis, nail changes have the strongest association with arthropathy, particularly affecting the DIP joints.
In psoriatic arthritis, nearly 15% of patients will develop psoriasis AFTER the onset of arthritis.
The most common infections preceding reactive arthritis are Chlamydia, Salmonella, Shigella, Campylobacter, and Yersinia.
Crohn's disease articular manifestations tend to be asymmetric, migratory, and pauciarticular with large and small joint involvement.
Erythema nodosum and peripheral arthritis are both more common in Crohn's disease than ulcerative colitis.
In diffuse idiopathic skeletal hyperostosis (DISH), the anatomical location of ossification occurs along the anterior longitudinal ligament
A shorter disease duration and younger age are predictors of a major clinical response to TNF blockers in active ankylosing spondylitis
In psoriatic arthritis, a CRP >0.9 md/dl at diagnosis may predict an inadequate response to conventional DMARDS. #ACR2012
Eye involvement is common in spondyloarthropathies and usually involves the middle layer of the eye-uveal tract
Patients with IBD (Crohn’s and UC) spondyloarthritis tend to develop posterior uveitis more commonly than other spondyloarthropathies
Almost 40% of HLAB27+ ankylosing spondylitis patients will get anterior uveitis. Usually only one eye will be effected at a time.
Autoinflammatory disorders
Return to top
Muckle-Wells syndrome is caused by a defect in the CIAS1 gene. Patients have fevers, sensorineural deafness, recurrent hives, & amyloidosis
TRAPS patients (TNF receptor-assoc. periodic syndrome) experience attacks of fever, migratory rash, and periorbital edema, lasting 1-3 weeks
NOMID (neonatal onset multisystem inflammatory disease) symptoms include rash, arthritis, & chronic meningitis leading to neurologic damage.
PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis & adenitis) is seen in children. Fevers occurs periodically every 3–5 weeks
Amongst the periodic febrile syndromes, responsiveness to colchicine is relatively specific to familial Mediterranean fever (FMF).
Familial Mediterranean fever (FMF) patients who are lactose intolerant may develop dose-limiting side effects of colchicine.
Systemic AA amyloidosis is the most devastating long-term complication of FMF. Outcomes include nephrotic syndrome & chronic renal failure
Return to top
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.
Erosive osteoarthritis (EOA) is an aggressive subset of OA. The classic radiographic findings include “gull-wing” & “saw-tooth” deformities.
Osteoarthritis affects nearly 27 million people in the US, accounting for 25% of visits to PCPs, and half of all NSAID prescriptions.
Several clinical trials have demonstrated the benefit of quadriceps strengthening on pain and function in patients with OA of the knee.
Varus alignment (bow-legs) increases the risk of knee OA 5-fold in obese patients. Valgus alignment (knock-kneed) is not as destructive.
In obese patients with knee OA, losing even just one pound results in a 4-pound reduction in knee-joint load for each step.
Femoroacetabular impingement syndrome can be a cause of hip pain and premature osteoarthritis in young adults. Refer to an orthopedist.
Barefoot walking has been demonstrated to reduce the major force across the knee in patients with medial compartment knee OA.
Patients who undergo knee arthroplasty are at an increased risk of clinically important weight gain following surgery. http://bit.ly/106lCIE
Radiographic osteoarthritis is at least twice more common than symptomatic osteoarthritis
Laboratory tests
Return to top
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.
The sensitivity and specificity of anti-CCP reactivity for the diagnosis of rheumatoid arthritis is 74.0% and 94.5%, respectively.
Patients with polymyositis and anti-SRP antibodies have more cardiac involvement, a poor prognosis, and a poor response to therapy.
Rheumatoid factor (RF) describes an antibody (IgM, IgG, or IgA) which targets the Fc portion of IgG. Together, they form immune complexes.
Patients who have PM-Scl antibodies typically have an overlap syndrome of polymyositis or dermatomyositis with systemic sclerosis.
Serum IgA antiendomysial and anti-tissue transglutaminase antibodies are highly specific and sensitive for celiac disease.
Mi-2 antibodies are seen in patients with “classic” dermatomyositis, including Gottron’s papules, heliotrope rash, & “V” and “shawl” sign.
A prolonged aPTT suggests the possibility of an lupus anticoagulant (LA), but only about half of all patients with LA have an abnormal aPTT.
P-155 antibodies are directed against transcriptional intermediary factor & are most closely linked to malignancy associated dermatomyositis
10–20% of patients with Sjögren’s syndrome have anti-thyroglobulin antibodies and may go on to develop autoimmune thyroiditis.
The allopurinol hypersensitivity syndrome consists of rash, fever, hepatitis, eosinophilia, and renal failure. Mortality approaches 25%.
Rheumatoid arthritis patients with anemia and a ferritin greater than 100ng/ml do not have iron deficiency anemia.
C-reactive protein is normal in ~ 70% of patients w/ rheumatoid arthritis early in the disease course and even if elevated is non-specific.
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.
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
Screening for celiac sprue includes serologic testing with total IgA, IgA tissue transglutaminase or IgA endomysial antibody.
Up to 80% of Stiff Person Syndrome (SPS) patients have an autoantibody against glutamic acid decarboxylase (GAD).
Metabolic bone disease
Return to top
Osteoporosis accounts for approximately 1.5 million fractures in the United States each year
Osteoporosis: Approximately 1/3 of all vertebral fractures are painful but 2/3 are asymptomatic
Hip fractures are assoc w/ permanent disability in nearly 50% of patients and w/ 20% excess mortality rate compared to age-match controls
Osteoporosis: For each vertebral fracture, there can be a decrease in FVC by 9%, reducing pulmonary function significantly
Osteoporosis: An older patient is more likely to suffer a fracture compared to a younger individual with the same T-score
A patient needs a calcium (corrected for albumin lvl) X phosphorous product of at least 24 to properly mineralize bone
The most predictive factor for a future fall is a previous fall w/in the past 6 months. Almost all hip fractures occur as a result of falls
Patients on steroids fracture at a higher T-score than do patients with other types of osteoporosis
Radiographic signs of Gaucher disease include bone infarcts, osteopenia and “Erlenmeyer flask” deformity
Return to top
McArdle’s disease is the most common glycogen storage disease. Most patients have an elevated CK level and have myopathic changes on EMG.
The anti-synthetase syndrome is marked by myositis, Raynaud’s, ILD, & mechanic’s hands. Most often associated with anti-Jo-1 antibodies.
In Duchenne muscular dystrophy, there is a characteristic hypertrophy of the calves but no muscle tenderness.
Eosinophilia-myalgia syndrome is characterized by pruritus, cutaneous lesions, sclerodermoid changes, arthralgias, myalgias and eosinophilia
Anti-MDA5 autoantibodies are associated with amyopathic dermatomyositis. Patients are at increased risk for rapidly progressive ILD.
Anti-TIF1-gamma autoantibody positive dermatomyositis patients carry an increased risk for internal malignancies.
Dermatomyositis and Polymyositis patients with a normal CPK but elevated aldolase are more likely to have a malignancy
Muscle cramps, pain, or myoglobinuria brought on by exercise suggests a metabolic myopathy
Muscle sxs w/ short bursts of high-intensity exercise and the 2nd wind phenomenon are characteristic of a glycogen storage disease
Muscle sxs w/ prolonged low-intensity exercise are/or prolonged fasting suggests a defect in fatty acid oxidation (CPT II def most common)
Elevated resting lactate level and/or ragged red fibers on muscle biopsy are characteristic of a mitochondrial myopathy
The most common metabolic myopathies associated with myoglobinuria are CPT II deficiency and McArdles disease
The most common myopathies confused for polymyositis are acid maltase deficiency and limb-girdle muscular dystrophy
Children with symptoms of a muscle disease without rash almost always have a metabolic or genetic myopathy and not primary polymyositis
Consider phosphofructokinase deficiency (Tarui disease) in patients w/ exercise induced muscle sxs, elevated CK, and hemolytic anemia
Consider acid maltase deficiency (Pompe disease) in patients that appear to have polymyositis w/significant respiratory insufficiency
Forearm ischemic test: If lactate does not rise but ammonia does - defect in glycolysis (such as McArdles)
Forearm ischemic test: If lactate rises but ammonia does not - patient has myoadenylate deaminase deficiency
Forearm ischemic test: If pyruvate rises but lactate does not, the patient has lactate dehydrogenase-M subunit deficiency
Forearm ischemic test: in CPT II deficiency, both lactate and ammonium rise appropriately thus not a helpful test in the diagnosis
Skin ulcerations plus anti-155/140 antibodies in the setting of dermatomyositis suggest an associated underlying malignancy
Myositis patients with positive anti-PL-7 and anti-PL-12 are more likely to have severe ILD and mild or absent myositis
The presence of anti-SRP antibody is assoc with severe, steroid resistant polymyositis, muscle pain from necrosis, & cardiac involvement
Return to top
Diffuse infiltrative lymphocytosis syndrome (DILS) is a disorder that mimics Sjogren's and is seen in HIV patients.
Alport's syndrome is a default in type IV collagen which effects the basement membrane.
Caplan's syndrome describes lung nodules only in patients with both RA and pneumoconiosis related to mining dust (coal, asbestos, silica).
Susac's syndrome is a microangiopathy characterized by the triad of encephalopathy, branch retinal artery occlusions and hearing loss.
Cogan's syndrome hallmarks include interstitial keratitis and vestibuloauditory dysfunction. It is most commonly seen in young adults.
SAPHO syndrome is an inflammatory bone disorder assoc w/ skin changes. It stands for Synovitis, Acne, Pustulosis, Hyperostosis, & Osteitis.
Lupus pernio is a chronic raised indurated skin lesion associated with sarcoidosis. It has nothing to do with either lupus or pernio.
On a worldwide basis, the most common cause of Erythema nodosum is streptococcal infections (~20% of patients).
Multicentric reticulohistiocytosis is characterized by severe destructive arthritis and cutaneous papulonodular lesions.
Hypercalcemia occurs in 10% of patients with sarcoidosis and is caused by endogenous production of 1,25 OH Vit D in the sarcoid granuloma.
Pigmented villonodular synovitis is a benign neoplasm that typically presents as an intra-articular tumor. Bloody effusions are common.
Nephrogenic systemic fibrosis (NSF) is seen exclusively in patients with renal insufficiency who have undergone a gadolinium (contrast) MRI
Respiratory involvement (glottis or tracheobronchial tree) is a frequent finding in relapsing polychondritis and is the main cause of death.
Interstitial nephritis, manifest as a type 1 renal tubular acidosis, is the most common renal manifestation of Sjögren's syndrome.
Patients who have cold agglutinin syndrome frequently present with a low-grade autoimmune hemolytic anemia and acrocyanosis.
Lofgren’s syndrome is a form of sarcoidosis & includes the clinical triad of hilar lymphadenopathy, acute polyarthritis, & erythema nodosum.
Foreign bodies such as thorns can lead to chronic tenosynovitis, bursitis & aseptic monoarticular synovitis in relation to the puncture site
Kienbock's disease is also known as avascular necrosis of the lunate bone (wrist), or lunatomalacia.
Complex regional pain syndrome (CRPS) Type I, (formerly reflex sympathetic dystrophy (RSD)), does not have demonstrable nerve lesions.
Livedo reticularis is strongly associated with the occurrence of arterial ischemic events in the antiphospholipid antibody syndrome.
Those who develop Raynaud’s phenomenon later in life (age >40) are more apt to have secondary Raynaud’s phenomenon.
Patients with primary Sjögren’s syndrome and hypocomplementemia, particularly C4, are at increased risk for the development of lymphoma.
IV drug users are susceptible to septic arthritis with unusual organisms (gram negatives) and in atypical axial sites (sternoclavicular).
The arthropathy associated with hyperparathyroidism is characterized by subperiosteal bone resorption of the middle phalanges.
CPPD (pseudogout) can be associated with a wide range of metabolic disorders including acromegaly, thyroid, and parathyroid conditions.
A febrile patient with HIV and a recent onset of thigh pain and swelling most likely has pyomyositis.
The major cause of malabsorption in scleroderma is intestinal stasis w/ bacterial overgrowth. Patients are commonly managed with antibiotics
In patients with scleroderma and abnormal esophageal manometry, almost all will also have abnormal anorectal motility.
The most serious complication of pauciarticular JIA is uveitis or iridocyclitis (20% of JIA). ANA positive patients are at greatest risk.
Although controversial, the frequency of autoimmune thyroiditis (Hashimoto's) is reportedly increased in those with Sjögren's syndrome.
An isolated low DLco (on PFTs) in a patient with scleroderma (especially CREST) suggests pulmonary hypertension.
Polymyalgia rheumatica (PMR) is almost exclusively a disease of adults over the age of 50. Prevalence increases progressively with age.
Patients with RS3PE (remitting seronegative symmetrical synovitis with pitting edema) have sudden onset polyarthritis and are RF negative.
Diabetic cheiroarthropathy is a common complication of diabetes related to increased glycation and nonenzymatic browning of skin collagen.
Limited joint mobility in a patient with diabetes mellitus indicates increased risk for microvascular disease, especially retinopathy.
Unlike most other diabetic complications affecting the hand, diabetic cheiroarthropathy is painless.
Purpura, hypocomplementemia, and cryoglobulinemia are three key prognostic factors for adverse outcome in primary Sjogren's Syndrome.
Celiac disease is associated with arthritis in ~9% of patients. Typically nonerosive and usually responds to a gluten free diet.
Infection with parvovirus B19 has been associated with symmetrical polyarthralgia/ polyarthritis which can mimic rheumatoid arthritis.
The arthritis of acute rheumatic fever is usually migratory and affects predominantly the large joints.
In patients with RS3PE who don’t respond to low dose prednisone, consider the possibility of an underlying malignancy.
When evaluating a patient for Sjögren's, ask about dental health as poor dentition is associated with inadequate salivary production.
Pulmonary function tests in interstitial lung disease (ILD) typically show a normal or elevated FEV1/FVC ratio and a decreased DLCO.
Whipple's disease is caused by Tropheryma whipplei. Characterized by insidious onset of weight loss, diarrhea, arthralgias, & abdominal pain
Celiac disease associated arthritis typically involves the lumbar spine, hips, knees, and shoulders and remits with gluten-free diet.
Clubbed fingers & tender periostitis of lower extremities can be clinical signs of a lung tumor. Hypertrophic Osteoarthrophathy
MCTD combines features of scleroderma, myositis, SLE, and RA and most patients are positive for the anti-U1-RNP autoantibody.
Mixed connective tissue disease (MCTD) (aka Sharp Syndrome) was first described in 1972 by Gordon C. Sharp and colleagues.
Legg-Calve-Perthes disease is avascular necrosis of the hip due to insufficient blood supply. Most commonly affects young, overweight boys.
Osteopetrosis is caused by an osteoclast proton pump deficiency resulting in a failure of bone resorption while its formation persists.
Neuropathic arthropathy of hands & wrists due to cervical syringomyelia can result in articular deformities resembling rheumatoid arthritis
The most common arthritic manifestation of relapsing polychondritis is migratory tenosynovitis.
IgG4-related disease is a fibroinflammatory condition characterized by formation IgG4+ plasma cells, fibrosis, a swift response to steroids.
The pancreas was the first organ in which IgG4-related disease was identified, but it has now been described in virtually every organ system
Type 1 autoimmune pancreatitis (AIM) is an organ manifestation of IgG4-related disease. Type 2 AIM appears to be a disease of its own.
The leading cause of death in patients with diffuse systemic sclerosis is interstitial lung disease.
Osteoid osteoma is a solitary benign lesion of bone usually occurring in a long bone cortex. Presents in 2nd or 3rd decade of life.
In Sjogren's, presence of subpleural honeycombing is suggestive of usual interstitial pneumonitis (UIP), which portends the worst prognosis
Usual interstitial pneumonitis (UIP) is more commonly seen in patients with Sjogren syndrome secondary to RA and SLE rather than primary SS
Radiology findings in Wilson’s disease can reveal premature osteoarthritis, chondrocalcinosis, and chondromalacia patella. Knees most common
Weber-Christian disease (relapsing febrile nodular panniculitis) is an inflammatory infiltration of subcutaneous adipose tissue.
Mycoplasma hominis as an etiologic agent for septic arthritis in patients who have undergone genitourinary manipulation.
Neuropathic joints occur in 25% of patients with syringomyelia. The most common joint is the shoulder with about 80% occurrence.
Sparing of the epidermis and presence of mucin deposits differentiate scleromyxedema (lichen myxedematosus) from scleroderma and morphea.
A greater than 4% decline per year in bone mineral density on DEXA suggests treatment failure.
In a patient with diffuse scleroderma, anti-RNA polymerase III is the antibody most associated with an increased risk for renal crisis
Pulmonary HTN & interstitial lung disease are under recognized complications of systemic JIA that are frequently fatal http://bit.ly/13WQNuA
Acquired factor VIII inhibitor (aka acquired hemophilia A) is a complication of severe rheumatoid arthritis and systemic lupus erythematosus
Osteochondritis dissecans is a result of chronic microtrauma and represents a form of avascular necrosis that is small and focal.
Calciphylaxis is a rare, painful disorder of metastatic calcification most commonly occurring in patients with ESRD on dialysis
Skin biopsy can confirm a diagnosis of calciphylaxis but carries a significant risk of severe pain, poor healing, and superinfection
Osteomyelitis is seen more than 100X more frequently in sickle cell disease than in normal individuals
When palmar fasciitis presents in a woman, think ovarian carcinoma
Nontuberculous mycobacterial MSK infections most commonly present as hand tenosynovitis
Brucellosis caused by ingestion of unpasteurized dairy products usually presents with sacroiliitis and fever
HBV infection can present as an arthritis-urticarial syndrome: HCV infection can cause autoantibodies and polyarthritis
Wilson’s dz- autosomal recessive w/ incr copper deposition in brain, liver & joints (<50%) w/ premature OA in wrist, MCPs, knees & spine.l
Wilson’s dz- Dx by LOW serum ceruloplasmin, HIGH urinary copper, hepatic copper levels, or mutations in ATP7B gene