Rheumatology

It is a systemic disease characterized by symmetric joint inflammation (arthritis), and autoantibody formation.

Characterized by asymmetric joint involvement, asymmetric joint space narrowing, joint hypertrophy, and new bone formation (osteophyte)

• Seronegative spondyloarthropathies (SNSA) are a group of arthritides characterized by axial skeleton involvement (back pain), various degrees of peripheral joint arthritis, inflammation, and subsequent ossification of ligaments and tendons (enthesitis)
• This include ankylosing spondylitis, reactive arthritis, enteropathic arthritis, and psoriatic arthritis

It is a disease/condition manifested as inappropriate scar tissue formation (fibrosis) throughout the entire body including the skin, arteries, kidneys, GI tract, lungs, and heart resulting ins significant organ dysfunction and the characteristic skin changes.

• Idiopathic Inflammatory Myopathies
• These are autoimmune disease of the muscle manifesting as proximal muscle weakness without distal muscle weakness, facial weakness, or significant pain.
• Diagnosse: muscle biopsy

• extremities (hands) and neck
• It does not affect T/L/S spine.

• Spondyloarthropathy
• OA
• Crystalline

• Spondyloarthropathy (psoriatic)
• Crystalline
• Septic arthritis
• Acute Rheum. fever
• Sarcoidosis
• RA
• SLE
• PSS

• Cell count and differential
• Crystals
• Culture and gram stain, fungal, AFB

normal

200-2,000

2,000 - 100,000 (> 50% PMN)

> 50,000 (>75% PMN)

• Asymmetric joint involvement
• Asymmetric joint space narrowing
• Joint hypertrophy
• New bone formation (osteophyte)

• Not ill-appearing
• bony joint enlargement
• Heberden and Bouchard nodes
• Joint tenderness with passive ROM
• +/- noninflammatory effusion

• Symmetric joint swelling
• Constitutional symptoms -- look ill
• Morning stiffness > 1 hour

• Ill-appearing
• Ulnar deviation
• Boutonniere and Swan-neck deformity
• Limited joint range of motion
• Joint swelling, redness, warmth, and pain
• Extraarticular manifestations
• Rheumatoid nodule, and involvement of every

• 9-11 hgb, or 27-30 Hct.
• Anything lower than the above is likely not caused only by ACD. Need to look for other causes.

• MCP
• PIP
• Wrists (carpal bones)
• C-spine
• MTP
• Knees
• Hips
• Ankles
• Toes

• Periarticular osteopenia
• Marginal erosions -- where synovium attaches to bone
• Target joints
• Soft tissue swelling

Head of the 5th metatarsal

• MCP
• Wrist
• Ankles

• DIP
• PIP
• CMC
• hips
• Knees
• Spine
• Feer
• Toes

Bony enlargement with new bone formation (osteophytes)

Bone loss; periarticular osteopenia, marginal erosions

• Suppress inflammation,
• minimize joint damage
• preserve joint function

• Analgesics
• DMARDs
• Disease Modifying AntiRheumatic Drugs and Immunosuppressants/Cytotoxics

• Methotrexate
• Gold
• Sulfasalazine
• Hydroxycholoroquine
• Minocycline
• Leflunomide (Arava)

• The DMARD of choice for most patients with rheumatoid arthritis.
• If at least partially effective, it should be continued as other agents are added.
• Therapy inhibits folic acid metabolism and may cause stomatitis, nausea, and diarrhea.
• Folic acid supplementation may reduce side effects
• Most common severe adverse effect of methotrexate is hepatotoxicity
• Bone marrow suppression rarely occurs but may develop in elderly patients treated with low doses of this agent.
• Contraindications: liver disease, abnormal findings on liver chemistry studies, and regular alcohol consumption.

• Measuring serum methotrexate levels is not helpful in monitoring therapeutic efficacy.
• Order monthly liver chemistry studies and a CBC until the dosage is stable and every 4 to 8 months thereafter.

• Liver biopsy
• Decrease dose or discontinue therapy if LFT persistently elevated

• Azathioprine
• Mycophenylate mofetil

TNF-a antagonists -- Etanecept, Infliximab, Adalimumab

• infection. Screen for TB.
• drug-induced lupus?
• ms-like syndrome?

• (anti-CD20 mAb)
• B-cell antagonist for RA

• It is a DMARD used in the treatment of RA.
• As effective as methotrexate without the lung toxicity
• Can be used concomitantly with methotrexate.
• Very teratogenic
• Women who plan to become pregnant must discontinue this therapy and undergo a course of cholestyramine elimination therapy.
• Women should attempt pregnancy only when serum leflunomide levels are less than 0.02 mg/L on two occasions at least 14 days apart.
• Aminotransferase levels should be measured monthly to monitor for hepatotoxicity. If levels are persistently elevated or if the drug is not tolerated, the dosage of leflunomide should be decreased.

14 days

Rifampin increases level

Most common side effect is diarrhea and hair loss

• Similar to methotrexate but without the lung toxicity
• Avoid in ETOH, Hepatitis B and C due to risk of hepatotoxicity
• Bone marrow suppression
• Avoid in renal insufficiency/failure

Cholestyramine 8 g tid X 11 days

This drug is very tetratogenic and patient is not allowed to become pregnant while on this medication. However, if pregnancy occur there is another reason to eliminate this drug from the body, this is the best way to do it.

• SOAP BRAIN MD
• Serositis
• Oral ulcers
• Arthritis
• Photosensitive rash
• Blood dyscrasias
• Renal disorder
• ANA
• Immunologic disorder
• Neurologic disorder
• Malar rash
• Discoid rash

Patients must have 4 of 11 criteria observed by MD.

• Pleuritis
• pericarditis
• Peritonitis

Nonerrosive arthritis involving >2 peripheral joints (clinically indistinguishable from RA)

These are painless oral or nasopharyngeal ulcerations

Skin rash from UV irradiation in sunny days and also on cloudy days.

clouds don't filter out UV irradiation

• Coombs + Hemolytic anemia with reticulocytosis or
• Leukopenia <4,000 WBC on > 2 occasions or
• Thrombocytopenia <100,000

• Persistent proteinuria > 0.5 grams/day or
• Cellular casts or
• > 10 RBC/HPF but urine must be sterile

Culture it.

> 1:80

• Anti-ds DNA antibody or anti-SM antibody or antiphospholipid antibody (2 positive tests performed with at least a 12 week interval based on either:
• 1. abnormal serum AgG or AgM anticardiolipin ab or
• 2. lupus anticoagulant or
• 3. false positvie RPR or VDRL for > 6 months and confirmed by T. palladium immobilization or fluorescent treponemal antibody (FTA) absorption test.

• Seizures
• Psychosis

• Neither antibodies are not sensitive but are very specific (but not specific enough to be pathognomonic)
• Anti-DS DNA ab indicates patients ar increased risk for significant SLE renal disease and may parallel lupus activity in individual patients.

antiphospholipid ab = anticardiolipin ab = anti-beta-2 glycoprotein ab

• Antibodies to phospholipid bind to and activate platelets resultin in aggregation and thrombosis
• Antiphospholipid antibodies are procoagulants despite the misnomer of also causing the "lupus anticoagulant" (falsely prolonged PTT)
• Can occur as a primary or as part of SLE

• Arterial thrombosis
• Venous thrombosis
• Libman-Sachs Endocarditis
• Livedo reticualris
• Recurrent fetal loss
• Thrombocytopenia

• May be ANA (-) but with positive Anti-Ro and Anti-La (sjogren markers)
• Rash is serpeginous, with inflammatory border, but usually less severe disease.

• NSAID
• Corticosteroids
• Immunosuppressive

• NSAIDs
• Hydroxychloroquine
• DMARDs
• Corticosteroids
• Immunosuppressive drugs

• Topical steroids
• Systemic steroids
• Hydroxychloroquine
• Methotrexate
• Immunosuppressive drugs

1⁰ Sjogren's -- dry mucous membranes [(ocular, oral, vaginal (keratoconjunctivitis sicca)] 2⁰ to exocrine gland inflammation and dysfunction.

2⁰ Sjogren's -- is sicca in the presence of another autoimmune rheumatologic disease

• Incidence - 3.9/100.000 in Olmstead County, MN
• 50% are 1⁰ and 50% are 2⁰.
• 90% of the patients are women
• Age at onset - most common in middle age

• Decreased circulating T cells
• Increased circulating B cells
• Infiltration and destruction of glands by CD4+ T cells

• 75% patients have anti-SSA (anti-Ro) ab
• 40% patients have anti-SSB (anti-La) ab
• 66% have ANA
• 66% have RF

a test to objectively measure tear production

Xeroses (dry mucus membranes)

• Musculoskeletal -- arthralgias, myalgias
• Cutaneous -- dry skin, hyperglobulinemic purport, vasculitis
• Pulmonary -- Xerotrachea, pulmonary infiltrate
• GI -- Esophageal dysmotility, pancreatitis, hepatitis
• Renal -- RTA, intersticial nephritis
• Neuro -- Peripheral neuropathy, CN neuropathy (especially the 5th), CNS
• Hematologic -- leukopenia, anemia, lymphoma

1⁰ Sjogren's syndrome has between a 6x and 40X increased risk of developing non-Hodgkin's lymphoma (typically a B-cell lymphoma or MALToma).

• Heralded by the development of:
• - a monoclonal protein
• - new-onset leukopenia
• - new-onset anemia
• - loss of previously present autoantibodies (ANA, Ro, La, RF)

• Moisture replacement
• Secretory stimulants (secretagogues) stimulate muscarinic receptors in salivary glands and other organs, leading to enhanced secretion.
• Pilocarpine
• Cevimeline

Prednisone/immunosuppression do not improve mucus membrane gland secretion

• asthma
• narrow-angle glaucoma
• acute iritis
• severe CV disease
• biliary disease
• nephrolithiasis
• diarrhea
• ulcer disease

it doesn't work

• Necrotizing angiitis affecting small/medium-sized vessels characterized by granuloma and/or aneurysms at vessel bifurcations.
• Most common age 40-60 years
• Male:Female = 2:1
• 25% are caused by/related to Hep B virus antigenemia (Hep B sAg+)

• Onset is abrupt or gradual with constitutional symptoms
• GI tract: mesenteric vasculitis - any GI symptoms
• Cardiac: coronary arteritis resulting in (50%) MI, CHF, Tachycardia
• Skin: Vasculitic/vasculopathic rash: (50%) ischemic ulcers, livedo reticularis, palpable purpura
• PNS: multiple mononeuropathies (UE=LE), mononeuritis multiplex

• Caused by vasculitis of the vasa vasorum which supplies blood to the peripheral nerves.
• There is diffuse, scattered, individual motor and nerve involvement. Initially asymmetric but later will coalesce to look symmetric.

• GU: necrotizing glomerulonephropathy (50%) manifested as proteinuria, hematuria/RBC casts, new-onset HTN.
• Testicular pain/tender -- can diagnose PAN through blind biopsy of testicles.
• Arthralgias/myalgias (30%)

Lungs

biopsy of any involved tissue or angiogram

• steroids and cyclophosphamide (if the're not viremic and part of the 75% who don't have Hep B) or
• steroids and antiviral agents (if they have Hep B)

5-year survival when treated = 60%

• Eosinophilic vasculitis
• Multiorgan disease involving small/medium sized vessels in patients with allergies an/or asthma
• Most common in middle age
• Male > Female

• allergic rhinitis/sinusitis
• chest discomfort
• SOB
• asthma

• eosinophilia > 10% WBC
• inflammatory

• CXR shows transient patchy or nodular infiltrates
• --"I keep getting pneumonia", or "I have a pneumonia that moves around."
• Sinus X-ray shows opacification

Steroids

obtain biopsy of any involved tissue

• Two kinds
• Takayasu's arteritis (pulseless disease) and Temporal arteritis (cranial arteritis) are chronic vasculitis of aorta and large branches
• Histologically identical granulomatous inflammatory diseases (with multinucleate giant cells) of large/muscular arteries.

• Asymmetric BP - with differential > 10 mmHg
• Angina
• Aortic insufficiency 2⁰ to aortic root dilatation
• Bruits
• CNS ischemic symptoms
• New onset HTN 2⁰ renal artery stenosis

• headache
• dizziness
• amaurosis fugax
• diplopia

Angiogram or MRA

> 90% 5-year survival with treatment

• Steroids
• Angioplasty (if not inflamed)
• Bypass surgery

• > 50 years old (mean age = 70 years old)
• Female:male = 2:1
• Uncommon in black population (this is questionable)
• North >> South
• 50% of patients have polymyalgia rheumatica

• Headache
• Scalp tenderness +/- skin necrosis
• Enlarged fibrotic tender temporal artery
• Jaw/tongue claudication
• Visual symptoms / loss / diplopia
• Sore throat / cough
• Aortic arch syndrome with asymmetric BP/bruits
• Peripheral neuropathy

Get a PPD or evaluate for TB. May have to put patient on INH if PPD+ to avoid TB reactivation during treatment.

• Necrotizing granulamatous vasculitis involving small arteries/arterioles/venules with classic triad of:
• 1. Upper respiratory airway involvement (sinus)
• 2. Lower respiratory airway involvement (pulmonary)
• 3. Focal segmental glomerulonephritis (renal)

• Upper Respiratory airway (Sinus)
• Lower airway (Pulmonary)
• Focal segmental glomerulonephritis (Renal)

Wegener's, especially when accompanied by respiratory and renal symptoms.

• Wegener's or Churg Strauss (vasculitis)
• Relapsing polychondritis
• Sarcoidosis
• Congenital Syphillis
• Trauma
• Drug abuse

Middle-aged pt with weight less, fever, fatigue, multiple organ involvement (PNS, GU, Skin, GI), inflammatory labs, and HBsAg+

Middle-aged pt with allergies/asthma, sinus sxs, eosinophilia > 10% WBC, and systemic illness.

Young Asian woman with symmetric pulses, new HTN, bruits, vascular insufficiency symptoms

> 50 years old with weight loss, fever, fatigue, jaw claudication, vision change/loss, HA, asymmetric pulses, inflammatory labs with high ESR and PMR.

Young / middle-aged pt with pulmonary sxs, sinus sx, abnormal ua, inflammatory labs, and systemic illness.

• FUO
• Unexplained multisystem disease
• Unexplained renal abnormality (especially with a nephritic ua)
• Unexplained cardiac / GI / CNS ischemia
• Mononeuritis multiplex
• Suspicious rash ( any type of rash)

Short acting NSAIDs

• Acute or chronic renal failure
• Volume depletion
• Altered renal tubular handling of uric acid due to drugs, volume status, or endogenous metabolic products:
• a. Diurertic therapy
• b. low-dose salicylate therapy
• c. lactic acidosis
• d. ketoacidosis
• e. ethanole

Use colchicine or NSAIDs. These prevent flares associated with changes in uric acid. We treat for one month prior to initiating hypouricemic therapy and always begin urate-lowering drugs while on anti-inflammatory medication

• Patients who are undersecretors of uric acid and who do not have renal insufficiency, history of kidney stones, or tophi.
• Their use requires patients to drink > 1 gallon water/day.

allopurinol

• Pseudo-osteoarthritis -- 50%
• Pseudo-gout -- 25%
• Lanthanic (asymptomatic) --20%
• Pseudo-rheumatoid arthritis -- 5%
• Pseudo-neutropic joints -- rare

Associated with aging

the knee

• Chondrocalcinosis in 75%
• Calcification of cartilage
• Often associated with OA

• Arthrocentesis alone may be adequate
• Intraarticular corticosteroids
• NSAIDs
• Colchicine may be effective

Maintenance therapy with NSAID and / or colchicine

• Hypothyroidism
• Hyperparathyroid disease
• Hemochromatosis

Remember, CPPD is a disease of the old. A young person presenting with CPPD need to have other causes looked at.

• Also known as basic calcium phosphate crystal (BCP) crystal
• Associated with aging and:
• 1. An acute synovitis
• 2. Destructive arthropathy (Milwaukee Shoulder -- hemorrhagic shoulder effusion in elderly women)
• 3. Calcific tendinitis/bursitis
• 4. Tumoral calcinosis/heterotrophic calcification

• by electron microscopy or alizarin red stainining.
• Not seen on polarizing scope

• Hyperparathyroidism
• Milk alkali syndrome
• Renal failure/long term dialysis
• Scleroderma

Same as gout and pseudogout.

• Seronegative (absence of RF or other specific antibodies)
• A group of arthritides characterized by axial skeleton involvement (back pain), various degrees of peripheral joint arthritis, and inflammation and subsequent ossification of ligaments and tendons (enthesitis)
• They are associated with a variety of mucocutaneous and ocular inflammatory disorders.

• Onset in young adults
• Familial
• Inflammatory arthritis of spine or large (hips) and peripheral joints
• Peripheral arthritis, often asymmetric with "sausage" digits (dactylitis)
• Mucocutanious manifestations
• Uveitis
• Enthesopathy (enthesitis)
• HLA-B27 is associated with spinal and eye disease.

• Painless ulcers
• Circinate balanitis
• Keratoderma blennorrhagica
• Psoriasis

• Aortic insufficiency
• Conduction defects

Apical fibrosis

Axial with symmetric SI joint changes with minimal peripheral joint arthritis

• Spine fracture dislocation
• Cauda equina syndrome

Acute anterior uveitis in 25% of patients

• Cardiac
• Aortic insufficiency
• Conduction defects

• Lung
• Apical fibrosis

• GI
• IBS

• Musculoskeletal
• Axial with symmetric SI joint changes with minimal peripheral joint arthritis

• Neurological
• Spine fracture dislocation
• Cauda equina syndrome

• Ophthalmologic
• Acute anterior uveitis in 25% of patients

• Arthritis (asymmetric, oligarthritis
• Conjuntivitis
• Urethritis (may be sterile)

• Campylobacter
• Shigella
• Salmonella
• Yersinia
• Chlamydia

• Circinate balanitis
• Conjunctivitis
• Keratoderma blennorrhagica
• Painless oral ulcers

It is a painless lesion of the penis.

• Skin lesions on the hands and soles, and may spread to the scalp and trunk. It is indistinguishable from pustular psoriasis
• Usually a feature in Reactive arthritis also known as Reiter Syndrome

• Sacroiliitis
• Spinal fusion
• Bamboo spine
• Enthesitis

• Sacroiliitis
• Axial arthritis
• Rarely peripheral

• follows infection
• triad in classic form
• mucocutaneous lesions

• Continued emphasis on postural training (sleep without a pillow)
• Similar to other non-crystalline inflammatory arthropathies
• -- NSAIDs, sulfasalazine, methotrexate, leflunomide, TNF-inhibitors

• Limited scleroderma (formerly known as CREST)
• Diffuse scleroderma

• vinyl chloride
• bleomycin
• tainted rapeseed (canola) oil
• L-tryptophan
• Eosinophilic fasciitis

• Rare: 19-75 / 100,000 population
• Peak occurrence: 35-65 years old
• Females > males
• Choctaw Indians 469/100.000

• Inappropriate fibrosis of tissues and blood vessels
• Smooth muscle cells proliferate within the intima of small vessels (small arteries, arterioles, and capillaries), narrowing the lumen causing tissue ischemia

• Caused by vasospasm
• Tricolor change - white to blue to red
• Digiral pitting scars and loss of digital pads
• Gangrene and autoamputation
• Occurs in 90% of patients with scleroderma

• GI bleeding from telangiectasias
• malabsorbption
• 2nd most common organ system involved

• Scleroderma affects pts with diffuse PSS
• Scleroderma Renal Crisis only occurs in diffuse disease and appears to be related to steroid use.
• Characterized by:
• 1. Accelerated HTN
• 2. Active urine sediment (nephritic)
• 3. Microangiopathic hemolysis
• 4. Rapidly progressive renal failure

• Primarily in diffuse PSS
• Pericarditis and effusion in 40% of patients
• Band necrosis -- fibrosis of conducting pathways causing palpitations and dysrhtymias.

• 95% of patients with PSS have an ANA
• Ant-Scl -70 (anti-topoisomerase 1) is assoc. with diffuse PSS
• Anti-centromere ab is associated with limited PSS.
• Anti-Scl-70 is associated with a worse prognosis.

• Diffuse PSS has a 40-60% 10-year survival
• Limited PSS has a >70% 10-year survival (if no pulm HTN)
• Cardiopulmonary disease is the leading cause of death

• Diffuse skin involvement
• Late age at onset
• African-Americans or native Americans
• Presence of tendon friction rubs
• A diffusing capacity <40% of predicted value
• The presence of a large pericardial effusion
• Renal failure or proteinuria or hematuria
• Anemia
• Elevated ESR
• Abnormal ECG

Glomerulonephritis, more severe sle

Glomerulonephritis, CNS disease

Raynaud phenomenon, myositis, MCTD

SCLE, Sjogren syndrome, neonatal lupus

SCLE, Sjogren syndrome, neonatal lupus

*not as sensitive as anti-Ro

Arterial and venous thrombosis, recurrent fetal loss, thrombocytopenia

• Psychosis, depression
• 15% sensitivity

• Presenti in > 95% of patients with drug-induced lupus
• 70% sensitivity

• Presence of oral ulcerations that recur at least three times in 1 year and at least two of the following manifestations:
• 1. recurrent genital ulcerations
• 2. inflammatory eye disease
• 3. cutaneous lesions
• 4. positive results on a pathergy test (characterized by a papule developing 48 hours after insertion of a 20-gauge needle intradermally)

Calcium pyrophosphate dihydrate deposition disease.

Characteristic features include large, minimally inflammatory effusions that usually develop in the shoulder or knee, destruction of associated tendon structures, and chronic pain. Calcium apatite crystals may only appear as amorphous nonbirefringent crystalline clumps on synovial fluid analysis and therefore are not identified on routine examination.

Pseudogout manifests as acute or subacute attacks of warmth and swelling in one to two joints that resemble acute gouty arthropathy. Pseudogout is associated with inflammatory synovial fluid and the presence of CPPD crystals that are weakly positively birefringent and rhomboid in shape seen on polarized light microscopy.

• Pain caused by spinal stenosis is relieved by hunching over (back flexin such as climbing stairs) or pushing a cart.
• Pain caused by a protruding disc is relieved by back extension (such as descending stairs) and worsened by back flexion (such as ascending stairs).

Bursitis is worse with active movement. When subacromial, middle arc of abduction is painful

• Supraspinatus tendon impingement is worse with:
• Passive, full flexion
• Passive, internal rotation
• Active external rotation of the shoulder against resistance.

• 1. T > -1
• 2. T = -1 to - 2.5
• 3. T < - 2.5
• 4. Osteoporosis + fractures

BMD (bone mineral density), not Dexa scores

• Migratory arthritis or tenosynovitis that settles in either a single joint or multiple joints.
• In women, it tends to occur at menstruation or post menstruation
• Joint fluid cultures are positive < 25%. Therefore, usually diagnosed on vaginal, throat, or anal culture.
• Most common cause of monoarticular arthritis in sexually active adults < 35 years old.

IV ceftriaxone

• Seen in patients with DM and ETOH abuse
• Fibrous thickening of flexor tendons of the fingers that cause palmar pain and limited extension of fingers.

Pain from the groin to the buttock. Lateral hip pain is usually caused by bursitis

Still's disease

burning paresthesias between the 3rd and 4th toes.

no. If they have it, you have to investigate.

• Clinical Criteria
• 1. Vascular thromboses:One or more episodes of a vascular thrombotic event.
• 2. Pregnancy morbidity: One or more unexplained deaths of a morphologically normal fetus beyond the 10th week of gestation.
• One or more premature births of a morphologically normal neonate before the 34th week of gestation because of eclampsia or severe preeclampsia or recognized features of placental insufficiency.
• Three or more unexplained consecutive spontaneous abortions before the 10th week of gestation.

• Laboratory Criteria
• 1. Presence of lupus anticoagulant on two or more occasions at least 12 weeks apart.
• 2. Anticardiolipin antibody of IgG and or IgM isotype in medium or high titer on two or more occasions at least 12 weeks apart.
• 3. Presence of anti-β2-glycoprotein 1 antibody of IgG and or IgM isotype present on two or more occasions at least 12 weeks apart.

The diagnosis requires at least one clinical and one laboratory criterion.

Cyclophosphamide is not indicated for the treatment of active rheumatoid arthritis except in patients with rheumatoid vasculitis in whom major organ function is compromised.

A variant of sarcoidosis characterized by acute monoarticular arthritis typically involving the ankles, erythema nodosum, and hilar lymphadenopathy that usually has a good prognosis.

• Morning stiffness lasting longer than 1 hour
• Fatigue
• Anorexia
• Weight loss
• Loss of function
• Tenderness and swelling of numerous joints
• Elevated acute phase reactant levels
• Progressive joint damage visible on radiography

It typically manifests as subacute migratory polyarthralgia and arthritis; tenosynovitis, and pustular, vesicopustular, or papular lesions

Monthly leuprolide acetate injections administered 2 weeks before administration of each cyclophosphamide dose will induce a temporary menopause and have been shown to protect the ovaries from the effects of cyclophosphamide. This treatment will maintain fertility and provide contraception, although use of a nonhormonal form of contraception, such as a barrier method or placement of an intrauterine device, is recommended to further ensure that pregnancy does not occur. Leuprolide acetate therapy can be discontinued once remission of this patient’s renal disease has been achieved and she is switched from cyclophosphamide to mycophenolate mofetil (generally after 3 to 6 months).

• Hydroxychloroquine is usually effective in managing mild manifestations of SLE, including cutaneous and joint involvement. Also is an extremely effective disease-modifying agent in SLE and helps to prevent disease flares.
• Rarely, hydroxychloroquine causes an irreversible retinopathy, and regular ophthalmologic screening is indicated in patients using this agent.

The tumor necrosis factor α inhibitor etanercept may worsen disease activity in patients with SLE and is generally not used in this patient population.

• reducible joint deformities that mimic those in patients with rheumatoid arthritis but are not erosive
• usually seen in SLE and may be associated with low titers of rheumatoid factor and tendon laxity.

• A systemic disorder characterized by inflammation of cartilage with involvement of the ears, nose, larynx, trachea, and joints.
• can occur in conjunction with other autoimmune diseases such as vasculitis, rheumatoid arthritis, and systemic lupus erythematosus.
• may be associated with myelodysplastic syndromes.
• some patients have a rapidly fatal course characterized by airway inflammation and respiratory failure.

• Auricular inflammation is present in 85% of affected patients and consists of redness, swelling, and tenderness of the auricle
• hearing loss
• inflammation of the tracheal cartilage may result in upper-airway obstruction with stridor; bronchial chondritis, which can rapidly progress to airway collapse and respiratory failure, also may occur.
• valvulitis with aortic and/or mitral valve insufficiency
• aneurysm formation, particularly of the ascending aorta.
• inflammatory eye disease, including episcleritis, scleritis, or uveitis.

• Associated with inflammation of the auricular, nasal, and/or laryngeal cartilage, and the diagnosis is established by inflammation in two of these areas.
• If only one area is involved, two of the following features must be present: ocular inflammation, audiovestibular manifestations, and/or inflammatory arthritis, which need not occur simultaneously

A macrocytic anemia is suggestive of a myelodysplastic syndrome.

• High-dose corticosteroids
• Management of inflammatory airway disease may include methotrexate, azathioprine, or cyclosporine (this is second line).
• Tracheostomy

• Therapy with an ACE-I is indicated for scleroderma renal crisos in pregnant patients despite being associated with an increased risk to the fetus.
• Captopril must be used in this patient to preserve renal function, control blood pressure, and reduce mortality despite being associated with an increased risk to the fetus.

• Pregabalin
• Duloxetine

• Still's disease is an inflammatory disease characterized by polyarthritis and fever that spikes once or twice daily.
• The major criteria are fever that spikes once or twice daily, polyarthritis, and leukocytosis.
• Patients with AOSD also may have normocytic, normochromic anemia; elevated inflammatory markers; a markedly elevated serum ferritin level that may exceed 2500 ng/mL (2500 mg/L); and an absence of antinuclear antibodies or rheumatoid factor.

• Relapsing polychondritis is associated with inflammation of cartilaginous areas, including the trachea, airways, ears, and joints.
• May manifest as polyarthritis; cough; fever; nasal congestion and rhinorrhea; and, in rare cases, pericarditis.
• Relapsing polychondritis is unlikely in the absence of auricular inflammation or inflammatory eye disease.

• Methotrexate
• Despite an absence of evidence obtained from clinical trials, methotrexate has dominated therapy in patients with psoriatic arthritis for many years and is effective in those who have low risk for bone marrow or liver toxicity. In patients with psoriatic arthritis, methotrexate helps to control cutaneous and musculoskeletal manifestations; long-term therapy with this agent also is well tolerated.

• Best used in RA
• hydroxychloroquine has been associated with severe flares of psoriasis and should be avoided in patients with this condition.

• tapering of corticosteroids in patients with psoriatic arthritis may be associated with dramatic flares in skin disease; these agents therefore should be used with caution in this population group.
• NSAIDs such as ibuprofen may help to alleviate this patient’s pain and swelling involving the joints but are believed to similarly exacerbate psoriasis
• neither prednisone nor ibuprofen would slow the progression of this patient’s articular damage.

this agent is less effective than methotrexate for both skin and joint disease associated with psoriatic arthritis.

• It is characterized by the presence of inflammatory arthritis that manifests within 2 months of an episode of bacterial gastroenteritis or nongonococcal urethritis or cervicitis in a genetically predisposed patient
• Historically, what is now called reactive arthritis was previously called Reiter syndrome, which referred to the co-incidence of arthritis, conjunctivitis, and urethritis (or cervicitis).
• Only one third of affected patients have all three symptoms.
• usually has an asymmetric oligoarticular pattern and involves the lower extremities.
• may be associated with enthesitis, which commonly manifests as Achilles tendinitis (as seen in this patient), plantar fasciitis, and spondylitis.

Avoid live attenuated vaccines including those for varicella, herpes zoster virus, mumps, measles, and rubella

• It is well tolerated and has a good safety profile and significant disease-modifying properties.
• This is effective for skin and joint manifestations and helps to prevent disease flares.
• Hydroxychloroquine should be continued indefinitely to prevent disease reactivation, even if the disease has been quiescent for many years.

• NSAIDs can be used to relieve pain in patients with SLE who have arthralgia or serositis.
• Selective cyclooxygenase-2 inhibitors may increase the risk for thrombosis and therefore should be used with caution in patients with SLE who have antiphospholipid antibodies.

• Corticosteroids are the primary treatment for acute SLE. Low-dose systemic corticosteroids are beneficial in patients with mild cutaneous disease and joint involvement
• moderate-dose corticosteroids may be warranted in patients with more aggressive skin disease, serositis, or mild hematologic abnormalities other than leukopenia
• high-dose corticosteroids are indicated in patients with nephritis, cerebritis, vasculitis, and life-threatening hematologic abnormalities
• High-dose or intralesional corticosteroids may be indicated to treat discoid lupus until hydroxychloroquine therapy becomes effective.

• Cyclophosphamide, mycophenolate mofetil, and azathioprine have a steroid-sparing effect and have been shown to improve outcomes in patients with severe SLE, particularly those with renal involvement.
• In patients with lupus nephritis, combination therapy with monthly intravenous cyclophosphamide and high-dose corticosteroids is superior to corticosteroids alone
• Cyclophosphamide is associated with serious toxicity; therefore, after remission of renal disease has been achieved and maintained for 3 to 6 months, switching from cyclophosphamide to mycophenolate mofetil or azathioprine should be considered. Mycophenolate mofetil is as effective as cyclophosphamide in inducing remission of lupus nephritis.

Corticosteroids, hydroxychloroquine, and azathioprine should be continued if the patient's disease are controlled by these.

Cyclophosphamide, mycophenolate mofetil, methotrexate, warfarin, angiotensin-converting enzyme inhibitors, and bisphosphonates should not be used during pregnancy.

• Neonatal lupus affects 1% to 2% of children of mothers with anti-Ro/SSA or anti-La/SSB antibodies, independent of whether these women have SLE or Sjögren syndrome.
• Pregnant patients who have anti-Ro/SSA or anti-La/SSB antibodies should undergo regular fetal echocardiography starting at 16 weeks of gestation.

within 3 months of diagnosis

sulfasalazine or hydroxychloroquine

Hydroxychloroquine therapy alone has not been shown to retard radiographic progression of rheumatoid arthritis and therefore should be used only in patients whose disease has remained nonerosive for several years.

• Methotrexate is contraindicated in a patient with abnormal liver chemistry study results or underlying liver disease, or in those who regularly consume alcoholic beverages.
• Leflunomide is similarly associated with hepatotoxicity and should be avoided in patients who consume significant amounts of alcohol

• Use of methotrexate or leflunomide may benefit patients with early mild to moderate rheumatoid arthritis but is imperative in patients with rapid disease progression or functional limitations
• In the absence of contraindications, methotrexate with or without the addition of another DMARD should be instituted immediately in patients with erosive disease documented at disease onset.
• The methotrexate dosage should be rapidly escalated as tolerated.
• patients using methotrexate take folic acid, 1 mg/d.

• combination therapy generally is more effective than monotherapy and may include use of two or three DMARDs.
• Combination therapy with hydroxychloroquine, sulfasalazine, and methotrexate has been shown to be more effective than monotherapy with methotrexate or sulfasalazine plus hydroxychloroquine.

• biologic therapy should be initiated
• The initial biologic therapy should be a TNF-α inhibitor.
• This agent generally should be added to the baseline methotrexate therapy

• Screening for tuberculosis
• patients who test positive for latent tuberculosis should be treated with isoniazid before beginning biologic therapy.
• periodic purified protein derivative skin testing for tuberculosis is now recommended during treatment with a TNF-α inhibitor.
• Pneumococcal vaccination is indicated before initiation of therapy

No. It does not enhance their efficacy but poses a risk for toxicity

methotrexate, leflunomide, or a biologic agent

• low-dose prednisone, which generally is believed to be safe in pregnancy.
• Hydroxychloroquine and sulfasalazine also can be used during pregnancy

• RA and SLE
• Has a slow onset of action and may require 3 to 6 months of therapy to gain full efficacy.
• Contraindicated in patients with renal or hepatic insufficiency.
• Macular toxicity is a severe side effect but is unlikely at a dosage of 6.5 mg/kg/d or less and rarely occurs before completion of 5 years of treatment.
• Referral to an ophthalmologist for a baseline examination and routine monitoring every 6 to 12 months is indicated in patients using hydroxychloroquine.

• monitor for neutropenia and elevated aminotransferase levels every 1 to 3 months
• contraindicated in patients with sulfa allergy or glucose-6-phosphate dehydrogenase deficiency but is considered safe during pregnancy (category B agent in pregnancy)

• --Approved for the treatment of RA but is more commonly used as a corticosteroid-sparing agent in patients with SLE and systemic vasculitis.
• --Need periodic CBC and LFTs
• Patients with a genetic deficiency of thiopurine methyltransferase (TPMT), the primary enzyme responsible for metabolizing azathioprine, are highly susceptible to serious azathioprine toxicity, such as pancytopenia. Therefore, although this condition is rare, genotype testing for TPMT may be warranted before initiating azathioprine therapy

• Primarily used to treat lupus nephritis and systemic vasculitis and is an effective initial therapy for Wegener granulomatosis.
• Daily oral dose more potent but assoc with hemorrhagic cystitis, cytopenias, bladder cancer, and leukemia
• Monthly intravenous administration usually prevents toxicity and has become the gold standard for the treatment of lupus nephritis.
• Frequent CBC and UA, prompt evaluation of gross hematuria.

TNF-α inhibitor agents such as etanercept are indicated as first-line therapy for ankylosing spondylitis

muddy brown casts or tubular epithelial cell casts

• Nearly one third of patients with an inflammatory myopathy have the antisynthetase syndrome.
• This condition can have an acute or subacute onset and is characterized by fever; fatigue; Raynaud phenomenon; synovitis; interstitial lung disease; and scaly, rough, dry, darkened, cracked horizontal lines that develop on the palmar and lateral aspects of the fingers that are known as “mechanic’s hands.”
• Patients with antisynthetase syndrome have antisynthetase antibodies that are specific for an inflammatory myopathy. The most common antisynthetase antibody is the anti–Jo-1 antibody.

In patient's with mysositis undergoing long-term corticosteroid therapy, the addition of methotrexate helps to control muscle disease and allow further tapering of the corticosteroid dosage over time.

• Patients who require continuous oxygen therapy owing to chronic
• respiratory or cardiovascular disorders may not tolerate commercial air
• travel and should be assessed for the need for possible additional
• in-flight supplemental oxygen.
• In-flight PO2 can be predicted using published algorithms or determined by performing a hypoxia inhalation test.
• The hypoxia inhalation test involves placing the patient in either a hypobaric chamber or having the patient breath a 15% oxygen mixture at sea level for at least 15 minutes with continuous pulse oximetry and electrocardiographic monitoring.

• a specific disorder that combines clinical findings of systemic lupus erythematosus, systemic sclerosis, and polymyositis and is characterized by high titers of anti-ribonucleoprotein antibodies.
• It is characterized by Raynaud phenomenon, arthralgia, and myositis accopmanied by high titers of anti-Rnp antibodies

• Antimitochondrial antibodies are present in approximately 95% of patients with primary biliary cirrhosis.
• Elevated alkaline phosphatase levels are typical of this condition, which also usually is associated with fatigue, pruritus, and hepatosplenomegaly

• The classic triad for acute anterior uveitis is pain, sensitivity to light, and blurred vision; headache, tenderness, and
• tearing may also occur

Standard practice is to discontinue tumor necrosis factor α inhibitors in patients who develop cancers, including melanomas.

• The presence of fatigue and iron deficiency anemia in a patient with systemic sclerosis should raise suspicion for gastric antral vascular ectasia.
• also known as watermelon stomach
• Patients with systemic sclerosis may develop cutaneous telangiectasias as well as mucosal telangiectasias that involve the upper and lower gastrointestinal tract; the development of telangiectasias in the stomach is known as GAVE and is associated with chronic blood loss. Most cases of GAVE are idiopathic and occur in elderly women, but this condition may occur secondary to systemic sclerosis or cirrhosis.

1. Dermatomyositis and polymyositis

2. Inclusion body myositis

Patients with Churg-Strauss syndrome who have cardiac, gastrointestinal, renal, or central nervous system involvement should be treated with cyclophosphamide in addition to high-dose corticosteroids.

• 1. Tumor necrosis factor α inhibitors such as etanecept are indicated as first-line therapy for ankylosing spondylitis and usually are associated with a degree of symptomatic relief and improvement in inflammatory changes visible on MRI.
• 2. Many of the agents used in rheumatoid arthritis, including methotrexate, sulfasalazine, and low-dose prednisone, are beneficial in the treatment of peripheral inflammatory arthritis associated with ankylosing spondylitis. However, these agents do not significantly affect spinal involvement in the spondyloarthropathies.

• Patients with an inflammatory myopathy and features of systemic sclerosis, systemic lupus erythematosus, and rheumatoid arthritis accompanied by high titers of antiribonucleoprotein antibodies often have mixed connective tissue disease.
• characterized by features of systemic sclerosis, myositis, rheumatoid arthritis, and systemic lupus erythematosus and is by definition associated with high titers of antiribonucleoprotein antibodies. The condition has a 9:1 female predominance.
• diagnosis generally requires high titers of antiribonucleoprotein antibodies accompanied by three of the following features: Raynaud phenomenon, synovitis, swollen hands, and myositis.

• Nearly one third of patients with an inflammatory myopathy have the antisynthetase syndrome. This condition can have an acute or subacute onset and is characterized by fever; fatigue; Raynaud phenomenon; synovitis; interstitial lung disease; and scaly, rough, dry, darkened, cracked horizontal lines that develop on the palmar and lateral aspects of the fingers that are known as “mechanic’s hands.”Patients with antisynthetase syndrome have antisynthetase antibodies that are specific for an inflammatory myopathy. The most common antisynthetase antibody is the anti–Jo-1 antibody.
• The greatest concern in patients with this syndrome is the risk for developing interstitial lung disease.

• Age at disease onset ≤40 years
• Claudication of the extremities
• Decreased pulsation of one or both brachial arteries
• Difference of at least 10 mm Hg in systolic blood pressure between the arms
• Bruit over one or both subclavian arteries or the abdominal aorta
• Arteriographic studies showing narrowing or occlusion of the entire aorta, its primary branches, or large arteries in the proximal upper or lower extremities that is not related to arteriosclerosis, fibromuscular dysplasia, or other causesa

A diagnosis of Takayasu arteritis is established in patients who meet three or more of these criteria.

Takayasu arteritis has an initial inflammatory phase followed by a pulseless phase. The initial phase is characterized by fever, arthralgia, myalgia, malaise, and weight loss that can last weeks to months. ESR and C-reactive protein are elevated. The pulseless phase is characterized by symptoms of vascular insufficiency, such as arm or leg claudication, or hypertension that is usually caused by renal artery stenosis. Many patients with Takayasu arteritis do not seek medical attention until they enter this disease phase.

High-dose corticosteroid therapy is indicated in the inflammatory phase. Elevated inflammatory markers, constitutional symptoms, or evidence of progressive arterial narrowing indicate the need for treatment. Uncontrolled trials suggest that methotrexate and tumor necrosis factor α inhibitors are effective steroid-sparing agents. In addition, cyclophosphamide is used in patients with severe refractory Takayasu arteritis.After the inflammatory phase of Takayasu arteritis has been controlled, affected patients may still have symptoms of vascular insufficiency due to fixed arterial narrowing. Aspirin may be used in this setting, but some patients require vascular intervention with revascularization. The outcome of coronary artery bypass graft surgery, angioplasty, and stenting is not optimal in these patients, and revascularization is not indicated until inflammation has been controlled.

• a necrotizing vasculitis of the medium-sized arteries.
• Polyarteritis nodosa has a peak age of onset between 40 and 60 years. Approximately 50% of cases of polyarteritis nodosa are associated with hepatitis B virus infection, usually of recent acquisition. The disorders also occur, but less frequently, in patients with hepatitis C virus infection.

• Patients with polyarteritis nodosa typically present with fever, abdominal pain, arthralgia, and weight loss that develop over days to months. Two thirds of these patients have mononeuritis multiplex, and one third have hypertension, testicular pain, and cutaneous involvement including nodules, ulcers, purpura, and livedo reticularis.
• The kidneys, peripheral nerves, and heart also are commonly affected. Aneurysm formation is common, especially in the mesenteric vessels. Ischemia, not glomerulonephritis, causes renal disease in patients with this condition.
• Patients with polyarteritis nodosa usually have anemia, leukocytosis, and an elevated ESR. ANCA assays are almost always negative, particularly in patients with concomitant hepatitis B virus infection. In patients with a compatible clinical presentation, biopsy is generally taken from the skin or a sural nerve. Radiographic imaging of the mesenteric or renal arteries can also be used to establish a definitive diagnosis of polyarteritis nodosa. Characteristic findings of this condition include aneurysms and stenoses of the medium-sized vessels.

• High-dose corticosteroid therapy
• Patients with a poor prognosis or with disease that is not controlled by corticosteroids should receive cyclophosphamide in addition to corticosteroid therapy.
• Short-term high-dose corticosteroid therapy accompanied by an antiviral agent such as lamivudine is indicated in patients with concomitant hepatitis B virus infection.

• Polymyalgia rheumatica
• GCA
• Takayasu arteritis

• characterized by aching in the shoulders, neck, and hip girdle region; fatigue; and malaise that develop over weeks to months. ESR and C-reactive protein levels are elevated.
• Affected patients respond rapidly and dramatically to low-dose prednisone (10 to 20 mg/d).

• Mycophenolate mofetil is as effective as and safer than cyclophosphamide in treating diffuse proliferative glomerulonephritis in patients with systemic lupus erythematosus.
• In women of childbearing age, mycophenolate's safety profile, including lack of effct on ovarian function, makes is use preferable to cyclophosphamide.
• Mycophenolate is a pregnancy safety-category D drug because of its association with first-trimester pregnancy loss and congenital malformations, and women of childbearing age should use effective contraception while taking this agent.

• Inflammatory extrarenal manifestations of SLE are best treated initially with corticosteroids.
• High-dose corticosteroids are indicated in patients with nephritis, cerebritis, vasculitis, and life-threatening hematologic abnormalities.
• Cyclophosphamide is primarily indicated for severe visceral SLE (especially diffuse proliferative glomerulonephritis), severe central nervous system manifestations, or vasculitis.

Therapy with methotrexate plus antitumor necrosis factor therapy or methotrexate plus abatacept results in better outcomes in patients with rheumatoid arthritis compared with methotrexate monotherapy.

Teriparatide (recombinant human parathyroid hormone [1-34]) is indicated in men or postmenopausal women with very low bone mineral density (T-score ≤−3.5), low bone mineral density (T-score ≤−2.5) and a fragility fracture, and patients with fractures who continue to lose bone mineral density while taking bisphosphonates. Patients who cannot tolerate or have contraindications to bisphosphonate therapy would also be candidates for teriparatide.

• Begin DMARD within 3 months of diagnosis
• Monotherapy with hydroxycholoquine or sulfasalazine or combination therapy with these agents is indicated to treat early, mild, and nonerosive disease
• Hydroxychloroquine therapy alone has not been shown to retard radiographic progression of rheumatoid arthritis and therefore should be used only in patients whose disease has remained nonerosive for several years.
• Use of methotrexate or leflunomide may benefit patients with early mild to moderate rheumatoid arthritis but is imperative in patients with rapid disease progression or functional limitations. In the absence of contraindications, methotrexate with or without the addition of another DMARD should be instituted immediately in patients with erosive disease documented at disease onset. The methotrexate dosage should be rapidly escalated as tolerated up to 20 to 25 mg weekly. Experts also recommend that patients using methotrexate take folic acid, 1 mg/d.

• When adequate disease control is not achieved with oral DMARDs, biologic
• therapy should be initiated. The initial biologic
• therapy should be a TNF-α inhibitor. This agent generally
• should be added to the baseline methotrexate therapy, because
• the rate of radiographic progression has been shown to
• decrease with combination therapy.

• Approximately 75% of women with rheumatoid arthritis who become pregnant
• experience a spontaneous remission of symptoms that
• usually begins in the second trimester of pregnancy. During
• pregnancy, most women with rheumatoid arthritis can therefore
• safely discontinue therapy for this condition. However,
• pregnant patients with persistent disease activity may require treatment
• with low-dose prednisone, which generally is believed to be
• safe in pregnancy. Hydroxychloroquine and sulfasalazine also can
• be used during pregnancy, if necessary.
• Reinstiture DMARD therapy immediately after delivery unless the woman is breast feeding.
• In women with highly aggressive disease, breast feeding should be discontinues so that DMARD therapy can be resumed.

• Combination DMARD therapy is more effective than single-agent therapy. Patients
• commonly undergo 3 to 6 months of methotrexate therapy; if the clinical
• response is inadequate, sulfasalazine and
• hydroxychloroquine, or a tumor necrosis factor α (TNF-α) cyclooxygenase
• inhibitor, can be added.
• Oral DMARDs typically take 3 months to produce a clinical response and up to 6 months for a full response. Biologic DMARDs require less time to demonstrate efficacy.

• Measuring serum methotrexate levels is not helpful in monitoring therapeutic efficacy. Patients using methotrexate should undergo monthly liver chemistry studies and a complete blood count until the dosage is stable and every 4 to 8 months thereafter.
• Liver biopsy is indicated in patients treated with methotrexate who have persistently elevated liver chemistry study results or decreased serum albumin levels.
• In patients with persistently elevated liver study results, the methotrexate dosage should be decreased or therapy discontinued.

• Patients treated with sulfasalazine should be monitored for neutropenia
• and elevated aminotransferase levels every 1 to 3
• months. Gastrointestinal intolerance due to nausea or
• abdominal pain may occur, but an enteric-coated preparation is
• available.

• Leflunomide
• Mycophenolate mofetil