Rheumatology

Eduard E. Vasilevskis, M.D.

Kenneth H. Fye, M.D.

 

Bacterial (Septic) Arthritis

Synovial Fluid

Crystal-Related Joint Disease – Gout

Crystal-Related Joint Disease – Pseudogout

Joint Injection With Steroids

Ara Criteria For Diagnosis Of SLE

Drugs Associated With  SLE

Factors That Influence ESR

Autoantibodies In Rheumatic Disease

Classification Of Vasculitidies

Vasculitis Tips

Rheumatoid Arthritis

Giant Cell (Temporal) Arteritis

Dermatomyositis And Polymyositis

 

 

BACTERIAL (SEPTIC) ARTHRITIS

 

Unexplained inflammatory synovial fluid, particularly in a febrile patient, should be assumed to be infected until proven otherwise.

 

1.      When to consider: acute onset of monoarticular arthritis.

 

2.      Risk Factors: history of IVDU, indwelling catheters, osteoarthritis, rheumatoid arthritis (0.5% annual incidence), post arthroscopy, post-injection of joint (exceedingly rare), prosthetic joints, and immunocompromised hosts. 

 

3.      Gonoccocal:

• Microbiology:  Neisseria gonorrhoeae; usually young, sexually active patients.  Increased risk with late complement deficiency. 
• Clinical presentation: often characterized by migratory of additive polyarthralgia, fever, tenosynovitis, and dermatitis—“periarthritis syndrome.” 25-50% develop a mono- or oligoarthritis with purulent joint effusions.  Rarely involves axial joints.  80% of patients have a concomitant, asymptomatic genitourinary infection.  
• Work-up:

-        Obtain history of recent sexual contact.

-        Send cultures of appropriate sites — pharynx, joint (30% sensitive; do gram stain as well as culture and sensitivity), blood, rectum, urethra, cervix (50-80% sensitive).  You must specify that you are trying to culture for gonorrhea (Chocolate agar or Thayer-Martin media are needed).

• Treatment: cover empirically with ceftriaxone 1 g IV QD after cultures are drawn in a

      sexually active patient without crystals or other known cause of inflamed joint.  Remember to treat partners.

 

4.      Nongonococcal:

• Microbiology: 

-        S. Aureus: most common agent.

-        Streptoccal species: next most common.  Increased in patients with splenic dysfunction or status-post splenectomy.

-        Aerobic gram negatives: increased in patients with IVDU, diabetics, sickle cell disease, immunocompromised hosts.

-        Anaerobic organisms: trauma, immunocompromised, post-GI surgery.

-        Mycobacterial: HIV, immunocompromised, travel.

-        Fungal: HIV, immunocompromised hosts.

-        Spirochete: tick exposure.  

-        Multi-organism: Trauma

·        Clinical Presentation: knee in > 50% cases.  15-20% Polyarticular.  Polyarticular infections more likely to occur in those with RA or who are immunocompromised by drugs or systemic illness. IVDU patients have a predilection for axial joints.  Symptoms: rapid onset (hours to days) joint pain, warmth, and restricted motion.  Fever is age-dependent; only 10% of elderly patients are febrile.

·        Work-up:

-        Send synovial fluid for crystal examination, gram stain (50-70% sensitive), glucose, cell count and differential, culture and sensitivity (see table below for synovial fluid characteristics).

-        Obtain blood cultures. (50% sensitive).

-        Urinalysis and culture, CXR to investigate possible source.

-        Order x-rays to evaluate for possible osteomyelitis and joint destruction.

·        Differential diagnosis:

-        Other infectious causes: Lyme disease, TB, fungal arthritis.

-        Noninfectious causes: RA, reactive arthritis, psoriatic arthritis (all can have cell counts >50,000 with > 90% neutrophils).

-        Crystal-induced arthritis: gout, pseudogout. 

-        Infections outside the joint: osteomyelitis, bursitis. 

-        Intra-articular derangment: meniscal tear, fracture, hemarthrosis. 

·        Treatment:

-        Start empiric antibiotics before definitive results of culture because of the rapidly destructive nature of this condition. Antibiotic choice directed by history.  In adults, cover for staph, strep, and gonococcal arthritis (unless sexual contact can be excluded). Treatment length is 2 weeks of IV antibiotics followed by 2-6 weeks of oral antibiotics (a shorter course is acceptable only in gonococcal arthritis). 

-        Repeat aspiration of joint to prevent accumulation of synovial fluid and to document sterility/decrease in leukocyte count.  Knees require daily aspiration for up to 7-10 days.

-        Surgical drainage may be required in areas that are difficult to aspirate (hips, shoulders), with inadequate closed needle aspiration drainage, coexisting osteomyelitis, or if inadequate recovery by synovial fluid analysis on follow-up taps.

·        Outcome:

-        Highly variable depending on age, prior joint architecture, immune competence, and organism involved.

-        Monoarticular: 4-8% mortality.

-        Polyarticular: 30-40% mortality.

 

Carreno Perez L. Septic arthritis. Baillieres Best Pract Res Clin Rheumatol 1999; 13:37-58.

Ho G, Jr. Bacterial arthritis. Curr Opin Rheumatol 2001; 13:310-4. 

 

 

SYNOVIAL FLUID

 

	Normal	Non-inflammatory	Inflammatory	Septic
Color	Colorless	Xanthochromic	Yellow	Variable
Clarity	Transparent	Transparent	Translucent / opaque	Opaque
Volume (knee) (mL)	< 3.5	> 3.5	> 3.5	> 3.5
Viscosity	High	High	Low	Low / variable
WBC/mm3	< 200	200 – 3000	3000 – 50,000	> 50,000
PMNs	< 25%	< 25%	> 50%	> 75%
Protein (g/dL)	1-2	1-3	3-5	3-5
LDH	Low	Low	High	variable
Glucose (mg/dl)	Similar to blood	Similar to blood	> 25,  lower than blood	< 25, much lower than blood
Culture	Negative	Negative	negative	May be (+)
Crystals			May be (+)
Examples		·     OA ·     trauma, ·     Charcot joint ·     aseptic necrosis ·     SLE ·     rheumatic fever ·     Scleroderma ·     PMR ·     E. nodosum, ·     PAN ·     Amyloid	·    RA ·    gout/pseudogout ·    SLE ·    Scleroderma ·    dermatomyositis ·    polymyositis ·    viral arthritis ·    TM ·    ankylosing spondylitis ·    seronegative spondyloarthropathies ·    psoriatic arthritis ·    rheumatic fever ·    Behcet’s syndrome	·    bacterial ·    tuberculosis

 

·        The synovial fluid leukocyte count seen with a septic joint, crystal-induced arthritis, or other noninfectious inflammatory causes overlap considerably. The higher the WBC count (>50,000) and the greater the proportion of neutrophils (>90%), the higher the likelihood of septic arthritis.

·        Lower cell counts may be observed among immunocompromised patients and in infections due to mycobacteria, some Neisseria, and some gram positive organisms.

·        Noninflammatory fluids generally have < 3000 WBC/mm³ with fewer than 75% neutrophils.

 

 

CRYSTAL-RELATED JOINT DISEASE – GOUT

 

1.      Epidemiology:

·        Gender:  men > women.  Urate levels rise in women after menopause with parallel increase in affected.  Hyperuricemia = serum uric acid concentration > 7-8 mg/dl in males; > 6-7 mg/dl in females.

·        Age: peak age in fifth decade.

·        Risk factors: trauma, surgery, starvation, alcohol ingestion, dietary overindulgence, and drugs (NSAIDS, thiazide diuretics).

·        Family history: 20% report a family history.

 

2.      Pathogenesis:

·        Solubility: limit of solubility of uric acid in plasma about 6.7 mg/dl at 37°C.

·        Over-producers (10%): defined as > 800 mg uric acid/day on normal diet. 

-        Primary: purine pathway (idiopathic, HGPRT deficiency, increased PRPP synthetase activity).

-        Secondary: increased cell turnover (hematologic malignancies, psoriasis, Paget’s disease, chemotherapy), increased purine intake (EtOH), accelerated ATP degradation (ETOH, muscle over-exertion).

·        Under-excretors (90%):

-        Primary:  idiopathic.

-        Secondary:  renal insufficiency, inhibition of tubular urate secretion (ketoacidosis and lactic acidosis), enhanced tubular reabsorption (diuretics, and dehydration), drugs (cyclosporine, pyrazinamide, ethambutol, low dose ASA), lead, EtOH.

·        Uric acid levels: only 10-25% hyperuricemic patients will develop gout. At least 10% of patients have a normal uric acid at the time of the attack. Duration and magnitude of hyperuricemia directly correlates with likelihood of gouty arthritis and age of onset.

 

3.      Clinical Presentation:

·        Acute intermittent gout: rapid onset of warmth, swelling, erythema, and exquisite pain in affected joint.  90% of initial attacks are monoarticular (typically lower extremity) but then can progress to polyarticular.  Systemic symptoms of fever and malaise (not uncommon).  Most untreated patients with gout will experience a second attack within 2 years.

·        Chronic tophaceous gout: usually after 10 years of acute intermittent gout.  Persistent discomfort and swelling with intermittent flares.  Higher level of polyarticular involvement. 

 

4.      Diagnosis:

·        Uric acid level: Often not helpful. At least 10% of patients have a normal uric acid at the time of the attack.

·        Synovial fluid findings: only need a very small amount to make the diagnosis. Monosodium urate crystals are needle-shaped and negative birefringence (crystals parallel to the line of slow vibration of the red compensator are yellow and at right angles to it are blue).

·        Cell count and culture: the presence of crystals does not exclude a concomitant septic arthritis!  WBC usually 5,000-80,000 with neutrophil predominance.

 

5.      Treatment:

·        Acute therapy:

-        NSAIDs (such as indomethacin 25-50 mg PO TID) are rapidly effective.  Start with maximal dose of your preferred NSAID. 

-        Colchicine:  Relief of pain < 48 hours.  Inhibits polymerization of microtubules, thus disrupting chemotaxis and phagocytosis.  Administer as 0.5-0.6 mg tabs hourly until pain improved, GI toxicity, or maximum dose of 6.0 mg reached.  Never use IV colchicine.  IV colchicine use is often associated with serious toxicity (renal failure, granulocytopenia, cardiopulmonary failure, death).   

-        Steroids: intra-articular injections or oral steroids can be used in patients with severe attacks or who have renal insufficiency and cannot tolerate NSAIDs. 

·        Prophylactic therapy:

-        Lifestyle modification: change diet, increase hydration, eliminate EtOH, and change inciting medications.

-        Risk factor modification: As gout is often associated with hypertension, obesity, hyperlipidemia, and ethanol abuse, one goal should be to prevent and/or treat these conditions.

-        Allopurinol: use in over-producers, tophus formation, and nephrolithiasis. 300 mg PO QD; adjust for renal insufficiency, age.  Worsens gout if started during acute attack.

-        Probenecid: use in under-excretors with normal GFR, and no history of nephrolithiasis. 500 mg PO BID then titrated up to target urate concentration (4-5mg/dl).  Inhibits excretion of multiple drugs (penicillin, indomethacin, dapsone, etc.).

-        NSAIDs (indomethacin, ibuprofen or naprosyn) can be used to prevent flares during initiation of hypouricemic therapy. Treatment can be discontinued after normal urate levels have been obtained, generally in 6-12 weeks.

-        Colchicine (0.5 mg PO BID):  Use only in combination with anti-hyperuricemic agents as drug may mask development of tophi.

 

Agudelo CA, Wise CM. Gout: diagnosis, pathogenesis, and clinical manifestations. Curr Opin Rheumatol 2001; 13:234-9.

 

CRYSTAL-RELATED JOINT DISEASE – PSEUDOGOUT

 

1.      Also known as calcium pyrophosphate dihydrate (CPPD) deposition disease.

 

2.      Epidemiology:

• Up to 4% adult population.
• Increased prevalence with age.

 

3.      Pathogenesis: possibly related to elevated synovial fluid PPi concentration contributed by articular chondrocytes.  Not determined by systemic concentrations of minerals, but likely local factors. 

• Idiopathic
• Hereditary: usually autosomal dominant inheritance.
• Metabolic: definitely associated with hemochromatosis, hyperparathyroidism, hypophosphatemia, and hypomagnesemia.  Probable association with hypothyroidism.  Possible association with gout.

 

4.      Clinical Presentation:

• May be asymptomatic.
• Pseudogout: 25% patients with CPPD present with gout-like symptoms.  Inflammation in one or more joints lasting for several days to 2 weeks.  One half involve the knees.
• Pseudo-rheumatoid: 5% of CPPD patients present with multiple joint involvement with symmetric distribution.  May also have morning stiffness, synovial thickening, and flexion contractures.  10% may have low RF titers, though radiographically more typical of osteoarthritis.
• Pseudo-osteoarthritis (progressive degeneration): 50% with progressive degeneration of various joints.  Knees most commonly affected followed by wrists.  Symmetric involvement is the rule, thought degeneration may occur at different rates.  Flexion contractures common. 
• Pseudo-neuropathic joint disease:  Acute neck pain from odontoid process calcification.  Ligamentum flavum involvement and chondroid metaplastic growth may encroach upon spinal cord.

 

5.      Diagnosis:

• Synovial fluid analysis reveals positively birefringent CPPD crystals by polarized light microscopy. They are rhomboid shaped and more difficult to detect because they are weakly birefringent. As opposed to monosodium urate crystals, CPPD crystals are blue when parallel to the line of slow vibration of the red compensator ((+) birefringence).
• Radiographic: Typically punctate or linear densities in articular hyaline or fibrocartilaginous tissues.
• Chondrocalcinosis is characteristic but not specific for CPPD

 

6.      Treatment:

• Patients with CPPD should undergo the following screening tests: calcium, phosphorous, magnesium, alkaline phosphatase, ferritin, iron, TIBC, TSH, and uric acid.
• Treatment of pseudogout involves treatment of any underlying metabolic disease, joint aspiration, NSAIDs, local or systemic corticosteroids.

 

 

JOINT INJECTION WITH STEROIDS   

 

1.      Indications: usually palliative, local, and temporary.  Expected improvement in 1-7 days with effect lasting from weeks up to 12 months or more.

• Rheumatoid arthritis: not primary therapy but may be used as adjunct to systemic therapy.
• Spondyloarthropathies such as ankylosing spondylitis, Reiter’s, psoriatic arthritis
• Crystal-induced arthritis: especially useful when NSAIDs are contraindicated.
• Osteoarthritis: especially in the setting of large effusions.

 

2.      Contraindications:

• Infection in or near joint.
• Concurrent bacteremia.
• Existing severe joint destruction or unstable.
• Failure of prior intra-articular steroids, or multiple recent injections.

 

3.      Adverse effects:

• Iatrogenic infection (rare).
• Steroid arthropathy/progressive joint deterioration.
• Tendon rupture/soft tissue atrophy/nerve damage if joint is missed.
• Systemic absorption.

 

4.      Dose: there are multiple preparations.  Prolonged effect with hexacetonide (Aristospan®). No consensus on dose.  In general the larger the dose, the more aggressive the joint protection should be and less frequent injections.

 

Size of joint	Example	Amount of Aristospan® or equivalent steroid dose.
Large	Knee, ankle, shoulder	20-60 mg
Medium	Elbow, wrist	10-30 mg
Small	MCP, IP, MTP	< 5-15 mg

 

 

ARA CRITERIA FOR DIAGNOSIS OF SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

 

4 or more manifestations present serially or simultaneously.  Remember that these are simply “criteria”.  Always use your clinical judgement in evaluating a patient for potential lupus.

 

Criterion	Definition
1.      Malar rash	Fixed malar erythema, flat or raised, tending to spare the nasolabial folds
2.      Discoid rash	Erythematous raised patches with adherent keratotic scaling and follicular plugging
3.      Photosensitivity	Skin rash as a result of unusual reaction to sun-light
4.      Oral ulcers	Oral or nasopharyngeal ulceration, usually painless
5.      Arthritis	Non-erosive arthritis involving > peripheral joints — tenderness, swelling, or effusion
6.      Serositis	Pleuritis-convincing history of pleuritic chest pain or rub or evidence of pleural effusion OR Pericarditis-documented by ECG, rub, or evidence of pericardial effusion
7.      Renal disorder	Persistent proteinuria > 0.5 g/day or > 3+ if quantification not performed OR Cellular casts-may be red cell, hemoglobin, granular, tubular, or mixed
8.      Neurologic disorder	Seizures OR psychosis in the absence of offending drugs or known metabolic derangements (uremia, ketoacidosis, or electrolyte imbalance)
9.      Hematologic disorder	Hemolytic anemia-with reticulocytosis OR Leukopenia: < 4,000 total > 2  times OR Lymphopenia: <1500 > 2  times OR Thrombocytopenia: <100,000 in absence of offending drugs
10.   Immunologic disorders	Positive antiphospholipid antibody OR Anti-DNA OR Anti-SM OR false positive serologic test for syphilis
11.   Antinuclear antibody	Positive ANA, at any point in time, and in the absence of known drugs to be associated with  “drug-induced lupus” syndrome

 

Ruiz-Irastorza G, Khamashta MA, Castellino G, et al. Systemic lupus erythematosus. Lancet 2001; 357:1027-32.

 

 

DRUGS ASSOCIATED WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

 

1.      Definite association:

·        Chlorpromazine

·        Hydralazine

·        Isoniazid

·        Methyldopa

·        Procainamide

·        Quinidine

 

2.      Possible association:

·        Beta-blockers

·        Captropril         

·        Carbamazepine 

·        Cimetidine        

·        Ethosuximide    

·        Levodopa         

·        Lithium            

·        Methimazole

·        Nitrofurantoin

·        Penicillamine

·        Phenytoin

·        Propothiouracil

·        Sulfasalazine

·        Sulfonamide

 

 

FACTORS THAT INFLUENCE ERYTHROCYTE SEDIMENTATION RATE (ESR)

 

Increase	Decrease
Anemia Hypercholesterolemia Female Sex Pregnancy High room temperature Inflammatory disease Chronic renal failure Obesity Heparin Tissue Damage (MI) Hypergammaglobulinemia Monoclonal gammopathy	Sickle cell disease Anisocytosis Spherocytosis Acanthocytosis Microcytosis Polycythemia Bile salts Clotting of blood samples > 2 hour delay in running test Low room temperature Hypofibrinogenemia Congestive heart failure Cachexia Cryoglobulinemia

 

Sox HC Jr, Liang MH.  The erythrocyte sedimentation rate. Guidelines for rational use.  Ann Intern Med. 1986 Apr;104(4):515-23.

AUTOANTIBODIES IN RHEUMATIC DISEASE

 

Frequency of specific antibodies in various rheumatic diseases (%)

 

Antibody	RA	SLE	Sjogren’s Syndrome	Systemic Sclerosis-Diffuse	CREST Syndrome	Polymyositis/ Dermatomyositis	Wegener’s
ANA	30-60	95-100	95	80-95	80-95	80-95	0-15
Anti-ds DNA	0-5	60	0	0	0	0	0
RF	72-85	20	75	25-33	25-33	33	50
Anti-Sm	0	10-25	0	0	0	0	0
Anti SS-A (anti-ro)	0-5	15-20	65-70	0	0	0	0
Anti SS-B (anti-la)	0-2	5-20	60-70	0	0	0	0
Anti-Scl 70	0	0	0	1	50	0	0
Anti-centromere	0	0	0	1	80-95	0	0
Anti-Jo-1	0	0	0	0	0	20-30	0
ANCA	0	0-1	0	0	0	0	93-96

 

·        ANCA directed against protease 3 strongly suggests a diagnosis of Wegener’s, while ANCA directed against myeloperoxidase favors a diagnosis of microscopic polyarteritis.

 

 

CLASSIFICATION OF VASCULITIDIES

 

Most patients with vasculitis present initially as diagnostic dilemmas, often with non-specific systemic symptoms, single or multi-organ dysfunction. The diseases are classified by vessel size—however there is overlap, as many involve several vessel sizes.

 

Organ system	Large Vessel	Medium Vessel	Small Vessel
	·        Takayasu’s arteritis ·        Giant cell arteritis ·        Kawasaki’s disease (Mucocutaneous syndrome)	·        Polyarteritis nodosa ·        Kawasaki disease ·        Isolated CNS vasculitis ·        Thromboangiitis obliterans	·        Churg Strauss (anti-MPO) ·        Wegener’s granulomatosis (anti-PR-3) ·        Microscopic polyangiitis (anti-MPO) ·        Henoch-Schonlein purpura ·        Essential cryoglobulinemia ·        Hypersensitivity ·        Behcet’s ·        Goodpastures
·        Skin	·        Ischemia	·        SQ nodules ·        Ulcers ·        Livedo	·        Palpable purpura ·        Small infarcts ·        urticaria
·        Renal	·        High BP ·        Renal insufficiency ·        Infarction	·        High BP ·        Renal insufficiency ·        (glomerulonephritis)	·        Glomerulonephritis ·        (renal insufficiency) ·        (high BP)
·        Neuro	·        Focal CNS ·        TIA./CVA ·        polyneuropathy	·        Focal CNS ·        Diffuse CNS ·        TIA/CVA ·        Mononeuritis multiplex ·        polyneuropathy	·        Diffuse CNS ·        Meningeal ·        Polyneuropathy
·        Heart	·        Infarction	·        CHF ·        Infarction	·        Pericarditis
·        GI	·        Pain (angina) ·        N/V ·        GI bleed ·        Perforation ·        Infarction	·        Pain ·        N/V ·        GI bleed ·        Perforation ·        Hepatitis	·        Pain ·        N/V ·        GI bleed ·        Hepatitis
·        Joint	·        Arthralgia/itis	·        Arthralgia/itis	·        Arthralgia/it is
·        Eye	·        Retinal vasculitis	·        Retinal vasculitis
·        Muscle	·        Myalgia	·        Myalgia ·        Weakness	·        Claudication ·        Myalgia

 

 

VASCULITIS TIPS

 

1.      When to think of vasculitis:

·        Multi-organ disease.

• Systemic illness without clear cause.
• Unusual ischemic events:

-        Multiple sites.

-        Unusual sites.

• Associated glomerulonephritis, proteinuria, and/or renal insufficiency.
• Skin lesions: palpable purpura, skin nodules, skin ulcerations, livedo reticularis, gangrene.
• Sudden neurologic events: headache, encephalomyelitis, retinitis, seizures, ischemic syndromes, mononeuritis multiplex.

 

2.      Mimics of vasculitis:

·        Endocarditis

• Atheroemboli
• Coagulopathies
• Drug toxicities

 

Jennette JC, Falk RJ. Small-vessel vasculitis. N Engl J Med 1997; 337:1512-23.

 

 

RHEUMATOID ARTHRITIS

 

4 or more criterion needed to make diagnosis; must have #1-4 for > 6 weeks

 

Criterion	Definition
1.      Morning Stiffness	In/around joints, lasting > 1 hour before maximal improvement
2.      Arthritis of 3 or > joint areas	> 3 areas simultaneously have had soft tissue swelling or fluid; the 14 possible areas are R/L PIP, MCP, wrist, elbow, knee, ankle, and MTP joints
3.      Arthritis of the hand joints	> 1 area swollen in the wrist, MCP, or PIP joint
4.      Symmetrical arthritis	Bilateral PIP, MCP, MTP without absolute symmetry acceptable
5.      Rheumatoid nodules	Subcutaneous nodules over bony prominences, extensor surfaces, or in juxta-articular regions
6.      Serum rheumatoid factor	By any method in which result has been positive < 5 % of normal control subjects
7.      Radiographic changes	PA hand/wrists x-ray with erosions or bony decalcification in or adjacent to involved joints

 

Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet 2001; 358:903-11.

 

 

GIANT CELL (TEMPORAL) ARTERITIS

 

1.      Epidemiology: incidence is 150-250 per million in those > 50 years old. 

·        Age: mean age of onset is 69 years old with 90% of cases occurring after 60 years. 

·        Gender: 80% female; Ethnicity: Northern European.

 

2.      Pathogenesis: a chronic vasculitis involving large vessels with an elastic lamina.  Inflammation leads to vessel stenosis, occlusion, and ultimately necrosis. 

 

3.      Clinical presentation: a common cause of fever of unknown origin in the hospitalized patient.  The diagnosis should be considered in a patient > 50 with headache, abrupt loss of vision, symptoms of PMR, unexplained fever/anemia, high ESR.

·        Onset of symptoms tends to be gradual, but may be abrupt

·        Clinical features: jaw claudication (found in 34% patients) has the highest positive likelihood ratio (+LR) of 4.2.  Diplopia next most predictive feature with +LR of 3.4.  Fever, weight loss, fatigue; head pain (>2/3 patients; does not have to be temporal in location in ½ cases); visual loss (15-29% patients; impaired vision is an early manifestation, may become irreversible, will involve both eyes if untreated); 50% of patients also have polymyalgia rheumatica (aching/stiffness in shoulder/hip girdles/neck/torso and ESR> 40).  

·        Exam: tender/thickened cranial arteries with visible swelling/erythema, and may be pulseless; fundoscopic exam may show swollen pale disc and/or blurred margins.

 

4.      Diagnosis:

 

ACR Classification Criteria for a Diagnosis of GCA (3/5 criteria must be met)

1.      Age > 50 at disease onset 2.      Localized headache of new onset 3.      Tenderness or decreased pulse of temporal artery 4.      Erythrocyte sedimentation rate of > 50 mm/hour 5.      Biopsy which includes an artery and reveals a necrotizing arteritis with predominance of mononuclear cells or a granulomatous process with multinucleated giant cells

 

·        The above criteria are 94% sensitive and 91% specific.

·        If an elevated ESR is excluded but scalp tenderness and jaw/tongue claudication are added, sensitivity increased to 95% and specificity remains at 91%.

·        Labs: ESR often > 100 but can be < 40 if mild or prior steroids; normocytic anemia, normal WBC, reactive thrombocytosis; microscopic hematuria (1/3 of patients); increased AST and alkaline phosphatase (25-35% of patients)

·        Biopsy: temporal artery biopsy should be performed in all suspected cases; ideally, biopsy is performed prior to treatment to maximize an accurate diagnosis but do not delay treatment if diagnosis is strongly suspected (steroids generally do not affect biopsy results for 48 hours).

 

5.      Treatment:  prednisone 0.7-1.0 mg/kg/day.  One month after clinical and laboratory parameters return to normal, begin to taper steroids.  Lack of response to steroids should prompt reconsideration of diagnosis. Long-term complications include late development of thoracic aortic aneurysms, renal artery stenosis, or other large vessel stenoses.

 

Salvarani C, Cantini F, Boiardi L, Hunder GG. Polymyalgia rheumatica and giant-cell arteritis. N Engl J Med 2002; 347:261-71.

Smetana GW, Shmerling RH. Does this patient have temporal arteritis? Jama 2002; 287:92-101.

 

DERMATOMYOSITIS AND POLYMYOSITIS

 

1.      Epidemiology:

• The association between malignancy and myositis:

-        The frequency of malignancy in these patients is 15-25%, with a 3x greater risk for DM. However, the increased risk of malignancy is seen only in childhood DM and in adults over 50 years of age.

-        The types of malignancy parallel the distribution in the general population.

-        Malignancy can be diagnosed before, at the time of, or after the diagnosis of myositis, with a peak incidence in 2 years before and after the development of myositis.

-        Age appropriate evaluation for malignancy should be conducted, with continued surveillance for 2-3 years following the diagnosis of myositis.

 

2.      Clincial Presentation:

·        Symmetric proximal muscle weakness (the most common presenting sign). Note: It is important to distinguish true muscle weakness from functional motor impairment not due to loss of muscle power. True muscle weakness is associated with inability to perform tasks—climbing stairs/combing hair. Muscle bulk is usually preserved in myopathies and muscle tenderness is not present—with some exceptions.

·        At least seven characteristic skin manifestations of dermatomyositis distinguish it from polymyosisits.  These skin findings include:

-        Heliotrope rash (red/violaceous eruption of upper eyelids).

-        Gottron’s papules (nonscaling, violaceous red eruption over extensor surfaces of  MCP, PIP, DIP).

 

3.      Diagnosis:

·        History and clinical presentation.

·        Laboratory Features:  Elevated plasma muscle enzymes: CK, LDH, AST, ALT.

·        The most prevalent myositis-specific antibody is the anti-histidyl-t-RNA synthetase (anti-Jo-1 antibody). Found in roughly 20% of cases.

·        Myopathic changes on EMG.

·        Biopsy: The definitive test, though the negative predictive value only 85%.

·        Differential diagnosis: other conditions causing muscle weakness ± elevated muscle enzymes must be distinguished from DM/PM. These include motor neuron disease (ALS), myasthenia gravis, muscular dystrophies, inherited/metabolic/drug-induced/endocrine, and infectious and other inflammatory myopathies.

 

4.      Treatment: corticosteroids ± azathioprine/methotrexate.