101. Gout Flare

/GoutFlare · monoarthritis · polyarticular · difficult-to-control · monosodium urate crystals · treat the flare first (don't start/stop urate-lowering mid-flare), exclude septic joint · Super Compact

Sx: acute, exquisitely painful, red, swollen, warm joint over hours — classically first MTP (podagra), also midfoot/ankle/knee; can be polyarticular (esp longstanding/tophaceous/elderly on diuretics); low-grade fever + leukocytosis possible (mimics infection); tophi in chronic disease · (the one thing you must not miss is septic arthritis — a hot joint with fever is a septic joint until an aspirate proves otherwise, and gout and infection can coexist, so when in doubt, tap it)

Neg: denies missed septic arthritis (fever + hot joint → aspirate before assuming gout; crystals don't exclude infection) · denies starting OR stopping urate-lowering therapy mid-flare (destabilizes — continue it if already on it, don't start it acutely) · denies missed precipitant (diuretic, dehydration, alcohol, surgery, acute illness, purine load) · denies NSAID use in CKD/heart failure/GI bleed · denies missed CPPD (pseudogout — different crystal)

SHx: prior gout flares + frequency, urate-lowering therapy + adherence, tophi, CKD/cardiovascular/metabolic syndrome, diuretic use (thiazide/loop), alcohol, diet (purine-rich, fructose), recent surgery/illness/dehydration, transplant/cyclosporine, prior allopurinol reaction

Etiology: monosodium urate crystal deposition from chronic hyperuricemia → acute inflammatory response (NLRP3 inflammasome → IL-1β); flares precipitated by rapid urate shifts (starting/stopping urate-lowering, diuretics, dehydration, alcohol, purine load, surgery, acute illness, trauma); risk from underexcretion (CKD, diuretics) or overproduction

RF: hyperuricemia · male/postmenopausal · CKD · diuretics · alcohol · obesity/metabolic syndrome · purine-rich diet · diuretics/cyclosporine · prior flares/tophi

Data: arthrocentesis with synovial fluid analysis is definitive: NEGATIVELY birefringent needle-shaped monosodium urate crystals (and cell count + Gram stain + culture to EXCLUDE infection) · serum uric acid (may be normal/low during a flare — don't exclude gout on it), CBC, CRP/ESR (inflammation), renal function (drug choice); imaging (US double-contour sign, dual-energy CT) if diagnosis unclear; assess for septic arthritis if any doubt

DDx: gout · septic arthritis (must exclude — can coexist) · CPPD/pseudogout (positively birefringent rhomboid crystals) · reactive arthritis · cellulitis · trauma/hemarthrosis · psoriatic/other inflammatory arthritis · osteoarthritis flare

Home Meds: CONTINUE urate-lowering therapy if already on it (do NOT stop during a flare); review diuretics (consider alternatives); reconcile; renally dose flare medications; do NOT start allopurinol/febuxostat during an acute flare (start after resolution, with flare prophylaxis)

Plan

CONSULT: Rheumatology (difficult-to-control, polyarticular, diagnostic uncertainty, urate-lowering initiation/refractory) · Orthopedics (if septic joint suspected — aspiration/washout) · Nephrology (CKD limiting drug options)

– FIRST exclude septic arthritis if fever/systemic signs/diagnostic doubt: arthrocentesis with cell count + Gram stain + culture before assuming gout (see the septic-vs-inflammatory arthritis approach); crystals do not rule out infection
– TREAT THE ACUTE FLARE — choose ONE first-line agent based on comorbidities (start early; the sooner, the better):
  • NSAID (if no CKD/CHF/GI bleed/anticoagulation): naproxen 500 mg PO BID OR indomethacin 50 mg PO TID until resolution, then taper
  • Colchicine (if early, <36 h from onset; avoid in severe CKD/drug interactions): 1.2 mg PO once then 0.6 mg 1 h later, then 0.6 mg daily–BID (low-dose — AGREE trial; renally adjust)
  • Glucocorticoid (preferred in CKD/CHF/contraindications to NSAID-colchicine): prednisone 30–40 mg PO daily then taper over ~7–10 days, OR intra-articular triamcinolone for a single accessible joint (after infection excluded)
  • IL-1 inhibitor (anakinra) for refractory/multiple contraindications per rheumatology
– POLYARTICULAR or severe: systemic glucocorticoid (or combination therapy) per rheumatology
– CONTINUE existing urate-lowering therapy through the flare; do NOT start it acutely (start ~2 weeks after resolution with concurrent flare prophylaxis — low-dose colchicine or NSAID for 3–6 months to prevent mobilization flares)
– ADDRESS PRECIPITANTS: hydration, review/replace diuretics, alcohol/diet counseling, treat acute illness
– DIFFICULT-TO-CONTROL/TOPHACEOUS (outpatient transition): urate-lowering to target serum urate <6 mg/dL (<5 if tophi) — allopurinol (titrate, screen HLA-B*5801 in high-risk ethnicities for SJS/TEN), febuxostat, or uricosurics; pegloticase for refractory tophaceous
– The two rules that govern an inpatient gout flare are about what NOT to do. First, don't anchor on gout when there's a fever and a hot joint — tap it, because a septic joint destroys cartilage in days and the urate crystals you find don't exclude a coexisting infection. Second, don't touch the urate-lowering therapy as a knee-jerk: if the patient is already on allopurinol, keep it going through the flare, because stopping it causes a urate shift that prolongs the attack; and never start allopurinol in the middle of a flare, because the same shift will make it worse — wait a couple of weeks and cover with prophylaxis. Otherwise the flare treatment is simply picking one anti-inflammatory that fits the patient's comorbidities: NSAIDs for the otherwise healthy, colchicine if you catch it early, and steroids for the CKD or heart failure patient where NSAIDs are dangerous.
– PT/OT: joint rest acutely, then mobilization; assistive devices if functional impairment
– Trend: joint pain/swelling/range of motion, CRP/ESR, renal function (drug dosing), response to therapy, serum urate (for outpatient urate-lowering target)
– Escalation triggers: septic arthritis confirmed/suspected → urgent orthopedics + drainage + antibiotics (see septic-arthritis approach); refractory flare despite first-line → combination/IL-1 inhibitor + rheumatology; flare with severe systemic illness → reassess for infection/alternative dx; allopurinol hypersensitivity (rash/DRESS) → stop + urgent evaluation
– Discharge checklist: flare controlled + infection excluded + precipitants addressed; flare regimen with taper; continue or PLAN urate-lowering initiation (after flare resolves, with prophylaxis) to target urate <6; diuretic/diet/alcohol counseling; rheumatology + PCP follow-up; HLA-B*5801 screening plan if allopurinol; return precautions (recurrent flare, fever + hot joint — possible infection, medication side effects, rash)

101. Gout Flare

/GoutFlare · complete reference · monoarticular + polyarticular + difficult-to-control · exclude septic joint, treat the flare by comorbidity, don't start/stop urate-lowering mid-flare · Full Card

Symptoms / Associated Sx

• An acute, exquisitely painful, red, swollen, warm joint developing over hours — classically the first MTP (podagra), also the midfoot, ankle, or knee

• Can be polyarticular (especially in longstanding, tophaceous, or elderly disease, or with diuretics); a low-grade fever and leukocytosis are possible (mimicking infection); tophi in chronic disease

• The one thing you must not miss is septic arthritis — a hot joint with fever is a septic joint until an aspirate proves otherwise, and gout and infection can coexist, so when in doubt, tap it

Neg

• Pt denies a missed septic arthritis (fever with a hot joint → aspirate before assuming gout; crystals don't exclude infection)

• Pt denies starting or stopping urate-lowering therapy mid-flare (destabilizes it — continue it if already on it, don't start it acutely) and a missed precipitant (diuretic, dehydration, alcohol, surgery, acute illness, purine load)

• Pt denies NSAID use in CKD, heart failure, or GI bleeding and a missed CPPD (pseudogout — a different crystal)

Social History (SHx)

• Prior gout flares and their frequency, urate-lowering therapy and adherence, and tophi

• CKD, cardiovascular disease, or metabolic syndrome, diuretic use (thiazide, loop), alcohol, and diet (purine-rich, fructose)

• Recent surgery, illness, or dehydration, transplant or cyclosporine, and a prior allopurinol reaction

Main Etiology

• Monosodium urate crystal deposition from chronic hyperuricemia triggers an acute inflammatory response (the NLRP3 inflammasome → IL-1β)

• Flares are precipitated by rapid urate shifts (starting or stopping urate-lowering therapy, diuretics, dehydration, alcohol, a purine load, surgery, acute illness, trauma)

• Risk arises from underexcretion (CKD, diuretics) or overproduction

RF

• Modifiable: diuretics, alcohol, obesity or metabolic syndrome, and a purine-rich diet

• Non-modifiable: hyperuricemia, male or postmenopausal status, CKD, cyclosporine, and prior flares or tophi

Data

• Arthrocentesis with synovial fluid analysis is definitive: negatively birefringent needle-shaped monosodium urate crystals (and a cell count, Gram stain, and culture to exclude infection)

• Serum uric acid (may be normal or low during a flare — don't exclude gout based on it), CBC, CRP/ESR (inflammation), and renal function (drug choice)

• Imaging (ultrasound double-contour sign, dual-energy CT) if the diagnosis is unclear; assess for septic arthritis if there is any doubt

DDx

Gout · septic arthritis (must exclude — can coexist) · CPPD or pseudogout (positively birefringent rhomboid crystals) · reactive arthritis · cellulitis · trauma or hemarthrosis · psoriatic or other inflammatory arthritis · an osteoarthritis flare

Home Meds

• Continue urate-lowering therapy if already on it (do not stop it during a flare)

• Review diuretics (consider alternatives); reconcile medications; renally dose flare medications

• Do not start allopurinol or febuxostat during an acute flare (start after resolution, with flare prophylaxis)

Plan

CONSULT: Rheumatology (difficult-to-control or polyarticular disease, diagnostic uncertainty, urate-lowering initiation, refractory disease) · Orthopedics (if a septic joint is suspected — aspiration or washout) · Nephrology (CKD limiting drug options)

• First exclude septic arthritis if there is fever, systemic signs, or diagnostic doubt: arthrocentesis with a cell count, Gram stain, and culture before assuming gout (see the septic-versus-inflammatory arthritis approach); crystals do not rule out infection.

• Treat the acute flare — choose one first-line agent based on comorbidities (start early; the sooner, the better):

• • NSAID (if no CKD, CHF, GI bleed, or anticoagulation): naproxen 500 mg PO BID or indomethacin 50 mg PO TID until resolution, then taper.

• • Colchicine (if early, under 36 hours from onset; avoid in severe CKD or with drug interactions): 1.2 mg PO once then 0.6 mg 1 hour later, then 0.6 mg daily to BID (low-dose — the AGREE trial; renally adjust).

• • Glucocorticoid (preferred in CKD, CHF, or contraindications to NSAIDs and colchicine): prednisone 30–40 mg PO daily then taper over ~7–10 days, or intra-articular triamcinolone for a single accessible joint (after infection is excluded).

• • IL-1 inhibitor (anakinra) for refractory disease or multiple contraindications, per rheumatology.

• Polyarticular or severe disease: a systemic glucocorticoid (or combination therapy) per rheumatology.

• Continue existing urate-lowering therapy through the flare; do not start it acutely (start ~2 weeks after resolution with concurrent flare prophylaxis — low-dose colchicine or an NSAID for 3–6 months to prevent mobilization flares).

• Address precipitants: hydration, review and replace diuretics, alcohol and diet counseling, and treat acute illness.

• Difficult-to-control or tophaceous disease (outpatient transition): urate-lowering to a target serum urate below 6 mg/dL (below 5 if there are tophi) — allopurinol (titrate, screen HLA-B*5801 in high-risk ethnicities for SJS/TEN), febuxostat, or uricosurics; pegloticase for refractory tophaceous disease.

• PT/OT: joint rest acutely, then mobilization; assistive devices if there is functional impairment.

• Trend: joint pain, swelling, and range of motion, CRP/ESR, renal function (drug dosing), the response to therapy, and serum urate (for the outpatient urate-lowering target).

• Escalation triggers: septic arthritis confirmed or suspected → urgent orthopedics, drainage, and antibiotics (see the septic-arthritis approach); a refractory flare despite first-line therapy → combination or IL-1 inhibitor therapy with rheumatology; a flare with severe systemic illness → reassess for infection or an alternative diagnosis; allopurinol hypersensitivity (rash, DRESS) → stop and urgent evaluation.

• Discharge checklist: the flare controlled, infection excluded, and precipitants addressed; a flare regimen with a taper; continue or plan urate-lowering initiation (after the flare resolves, with prophylaxis) to a target urate below 6; diuretic, diet, and alcohol counseling; rheumatology and PCP follow-up; an HLA-B*5801 screening plan if allopurinol; return precautions for a recurrent flare, fever with a hot joint (possible infection), medication side effects, or rash.

Red Flags

• Fever with a hot joint → septic arthritis until an aspirate proves otherwise; crystals don't exclude coexisting infection.

• Starting allopurinol during an acute flare → a urate shift that worsens and prolongs it.

• Stopping established urate-lowering therapy during a flare → destabilizes it; continue it through.

• NSAIDs or colchicine in significant CKD → toxicity; use glucocorticoids instead.

• Rash or DRESS on allopurinol → hypersensitivity (SJS/TEN risk); stop immediately.

Senior IM Resident Pearls

• A hot joint with fever gets tapped. A septic joint destroys cartilage in days, and the urate crystals you find don't exclude a coexisting infection.

• Don't stop established urate-lowering therapy in a flare. Stopping it shifts urate and prolongs the attack — keep it going.

• Don't start allopurinol mid-flare. The same urate shift worsens it; wait ~2 weeks and cover with prophylaxis.

• Pick the anti-inflammatory by comorbidity. NSAIDs for the healthy, colchicine if caught early, steroids for CKD or heart failure.

• A normal uric acid doesn't exclude gout. Serum urate often drops during an acute flare — the crystal analysis is what makes the diagnosis.

• Cover the start of urate-lowering with prophylaxis. Mobilization flares are common in the first months; low-dose colchicine or an NSAID prevents them.

• Common mistake: calling a hot, swollen joint "just gout" without aspirating in a patient with fever — the missed septic arthritis is the costly error.

Rheumatology — Acute Joint

102. Septic vs Inflammatory Arthritis

/SepticVsInflammatoryArthritis · the acute swollen joint · ASPIRATE first — synovial fluid decides · treat septic as an emergency, don't let crystals fool you · Super Compact

Approach — the acute hot joint is "septic until the tap says otherwise." A single acutely swollen, painful, warm joint forces one question: is this infection (a joint-destroying emergency) or inflammation (crystal/autoimmune)? The answer comes from arthrocentesis, not from gestalt — and treatment for presumed septic arthritis starts before cultures return.

Sx: acute monoarthritis — pain, swelling, warmth, erythema, restricted motion; septic clues: fever, systemic illness, risk factors (prosthetic joint, recent procedure, bacteremia, IV drug use, immunosuppression, skin breach); inflammatory clues: prior similar episodes, known crystal/autoimmune disease, polyarticular pattern — but none reliably excludes infection · (the single most important reflex is to aspirate the joint before committing to a diagnosis — and crystals in the fluid do NOT rule out a concurrent septic joint, so a high cell count or positive Gram stain still means infection even if urate crystals are present)

Neg: denies treating a hot joint as crystal/inflammatory without aspirating (missed septic arthritis destroys the joint in days) · denies excluding infection just because crystals were seen (they can coexist) · denies delaying drainage/antibiotics in a septic joint · denies missing prosthetic joint infection (distinct workup/management) · denies missing gonococcal/disseminated GC in a young sexually active patient · denies missing endocarditis as a source

SHx: prior joint disease (gout/CPPD/RA), prosthetic joints, recent joint procedure/injection, IV drug use, immunosuppression, diabetes, skin/soft-tissue infection, bacteremia source, sexual history (gonococcal), tick exposure (Lyme), recent infection

Etiology: septic — hematogenous or direct bacterial seeding (S. aureus most common; gonococcal in young sexually active; gram-negatives; prosthetic-joint organisms) · inflammatory — crystal (gout/CPPD), autoimmune (RA, psoriatic, reactive, SLE), or other; reactive/post-infectious · the danger is that septic + crystal arthritis can occur together

RF (for septic): prosthetic joint · recent procedure/injection · bacteremia/endocarditis · IV drug use · immunosuppression/diabetes · pre-existing joint damage (RA) · skin breach

Data: ARTHROCENTESIS is the key test — synovial fluid cell count + differential, Gram stain, culture, crystal analysis · WBC interpretation: >50,000 (esp >100,000) with neutrophil predominance → septic likely; lower counts inflammatory — but overlap exists and a positive Gram stain/culture confirms infection regardless of crystals · blood cultures, CBC, CRP/ESR, lactate if septic; imaging (X-ray baseline, MRI/US for effusion/osteomyelitis); gonococcal NAAT/cultures if suspected

DDx: septic (bacterial) arthritis · gonococcal arthritis · prosthetic joint infection · gout · CPPD/pseudogout · reactive arthritis · RA/psoriatic/other inflammatory · Lyme arthritis · hemarthrosis · osteoarthritis flare · adjacent osteomyelitis/cellulitis

Plan

CONSULT: Orthopedic surgery (URGENT — joint drainage/washout for septic arthritis) · Infectious Disease (antibiotic selection/duration, prosthetic joint, gonococcal) · Rheumatology (inflammatory/crystal, diagnostic uncertainty) · ICU if septic/unstable

– STEP 1 — ARTHROCENTESIS before antibiotics (if feasible without delaying treatment in sepsis): send cell count + differential, Gram stain, culture, crystal analysis; obtain blood cultures; this single test drives the entire decision
– STEP 2 — IF SEPTIC ARTHRITIS suspected/confirmed (high cell count, positive Gram stain, or strong clinical suspicion) — treat as an emergency:
  • URGENT joint drainage (arthroscopic/surgical washout or serial aspiration per orthopedics — source control is essential)
  • Empiric IV antibiotics after cultures: vancomycin (MRSA coverage) PLUS a gram-negative agent (e.g. ceftriaxone, or cefepime if Pseudomonas risk); tailor to Gram stain/culture; gonococcal → ceftriaxone; prosthetic joint → ID + surgery (distinct pathway, often staged)
  • Duration typically ~2–4 weeks (longer for prosthetic/complicated) per ID, with IV-to-oral step-down
– STEP 3 — IF INFLAMMATORY (crystals present, low/moderate cell count, negative Gram stain, infection excluded): treat the specific cause — gout/CPPD → NSAID, colchicine, or glucocorticoid (see the crystal arthropathy approach); RA/other → flare management (see the relevant approach); reassess if not improving
– WHEN UNCERTAIN: treat empirically for septic arthritis until cultures + clinical course exclude it — the cost of a missed septic joint (rapid cartilage destruction, sepsis) far exceeds brief empiric antibiotics
– The acute hot joint is one of the cleaner "do this first" situations in medicine: aspirate it, because the synovial fluid — the cell count, the Gram stain, the crystals — answers the only question that matters, whether this is an infection that will eat the joint in days or an inflammatory process you can treat at leisure. The trap is letting crystals reassure you: finding urate or CPPD crystals does NOT exclude a septic joint, because the two coexist, so a genuinely high cell count or a positive Gram stain still means infection even with crystals floating in the fluid. When the picture is ambiguous, you commit to treating the septic joint — urgent drainage plus empiric vancomycin and gram-negative coverage — and let the cultures talk you out of it, because the downside of treating gout as infection for two days is trivial next to the downside of treating a septic joint as gout. And don't forget the special cases: the prosthetic joint and the young patient with disseminated gonococcal disease each run a different track.
– PT/OT: early mobilization after source control (septic); functional recovery; joint protection
– Trend: synovial fluid results, joint exam (pain/swelling/ROM), CRP/ESR, blood cultures/clearance, response to drainage + antibiotics (septic) or anti-inflammatory (inflammatory), systemic signs
– Escalation triggers: septic arthritis → emergent orthopedic drainage + IV antibiotics ± ICU; sepsis/septic shock → sepsis pathway + ICU; prosthetic joint infection → ID + orthopedics (staged); failure to improve on inflammatory treatment → re-aspirate/re-evaluate for missed infection; gonococcal disseminated → ID + ceftriaxone
– Discharge checklist: diagnosis established (septic vs inflammatory) + appropriate treatment underway; if septic: antibiotic regimen + duration (ID-directed) + IV-to-oral plan + source control done; if inflammatory: cause-specific therapy + follow-up; orthopedics/ID/rheumatology follow-up as relevant; return precautions (worsening joint, fever, spreading infection, inability to bear weight, systemic symptoms)

102. Septic vs Inflammatory Arthritis

/SepticVsInflammatoryArthritis · complete reference · arthrocentesis decides, treat the septic joint as an emergency, crystals don't exclude infection · Full Card

Approach — The Acute Hot Joint Is "Septic Until the Tap Says Otherwise"

• A single acutely swollen, painful, warm joint forces one question: is this infection (a joint-destroying emergency) or inflammation (crystal or autoimmune)? The answer comes from arthrocentesis, not from gestalt — and treatment for presumed septic arthritis starts before cultures return.

• Septic clues: fever, systemic illness, and risk factors (prosthetic joint, recent procedure, bacteremia, IV drug use, immunosuppression, skin breach).

• Inflammatory clues: prior similar episodes, known crystal or autoimmune disease, and a polyarticular pattern — but none reliably excludes infection.

• The single most important reflex is to aspirate the joint before committing to a diagnosis — and crystals in the fluid do not rule out a concurrent septic joint, so a high cell count or positive Gram stain still means infection even if urate crystals are present.

Symptoms / Associated Sx

• Acute monoarthritis — pain, swelling, warmth, erythema, and restricted motion.

• Fever and systemic illness raise concern for infection; prior similar episodes or known crystal or autoimmune disease suggest inflammation — but the overlap is real.

Neg

• Pt denies treating a hot joint as crystal or inflammatory without aspirating (a missed septic arthritis destroys the joint in days) and excluding infection just because crystals were seen (they can coexist).

• Pt denies delaying drainage or antibiotics in a septic joint and missing a prosthetic joint infection (a distinct workup and management).

• Pt denies missing gonococcal or disseminated gonococcal disease in a young sexually active patient and missing endocarditis as a source.

Social History (SHx)

• Prior joint disease (gout, CPPD, RA), prosthetic joints, and a recent joint procedure or injection.

• IV drug use, immunosuppression, diabetes, and a skin or soft-tissue infection or bacteremia source.

• Sexual history (gonococcal), tick exposure (Lyme), and recent infection.

Main Etiology

• Septic — hematogenous or direct bacterial seeding (S. aureus most common; gonococcal in young sexually active patients; gram-negatives; prosthetic-joint organisms).

• Inflammatory — crystal (gout, CPPD), autoimmune (RA, psoriatic, reactive, SLE), or other; reactive or post-infectious.

• The danger is that septic and crystal arthritis can occur together.

RF (for septic)

• Modifiable: a recent procedure or injection, IV drug use, and a skin breach.

• Non-modifiable: a prosthetic joint, bacteremia or endocarditis, immunosuppression or diabetes, and pre-existing joint damage (RA).

Data

• Arthrocentesis is the key test — synovial fluid cell count and differential, Gram stain, culture, and crystal analysis

• WBC interpretation: above 50,000 (especially above 100,000) with a neutrophil predominance → septic likely; lower counts inflammatory — but overlap exists, and a positive Gram stain or culture confirms infection regardless of crystals

• Blood cultures, CBC, CRP/ESR, and lactate if septic; imaging (X-ray baseline, MRI or ultrasound for effusion or osteomyelitis); gonococcal NAAT and cultures if suspected.

DDx

Septic (bacterial) arthritis · gonococcal arthritis · prosthetic joint infection · gout · CPPD or pseudogout · reactive arthritis · RA, psoriatic, or other inflammatory arthritis · Lyme arthritis · hemarthrosis · an osteoarthritis flare · adjacent osteomyelitis or cellulitis

Home Meds

• Hold immunosuppression if septic arthritis is confirmed (coordinate with the prescriber); reconcile.

• Renally dose antibiotics (ID-directed); continue or adjust chronic rheumatologic therapy per the diagnosis.

• Resume appropriate therapy once infection is treated or excluded.

Plan

CONSULT: Orthopedic surgery (urgent — joint drainage or washout for septic arthritis) · Infectious Disease (antibiotic selection and duration, prosthetic joint, gonococcal disease) · Rheumatology (inflammatory or crystal disease, diagnostic uncertainty) · ICU if septic or unstable

• Step 1 — arthrocentesis before antibiotics (if feasible without delaying treatment in sepsis): send a cell count and differential, Gram stain, culture, and crystal analysis; obtain blood cultures; this single test drives the entire decision.

• Step 2 — if septic arthritis is suspected or confirmed (a high cell count, a positive Gram stain, or strong clinical suspicion) — treat as an emergency:

• • Urgent joint drainage (arthroscopic or surgical washout or serial aspiration per orthopedics — source control is essential).

• • Empiric IV antibiotics after cultures: vancomycin (MRSA coverage) plus a gram-negative agent (e.g. ceftriaxone, or cefepime if there is Pseudomonas risk); tailor to the Gram stain and culture; gonococcal → ceftriaxone; a prosthetic joint → ID and surgery (a distinct pathway, often staged).

• • Duration typically ~2–4 weeks (longer for prosthetic or complicated disease) per ID, with IV-to-oral step-down.

• Step 3 — if inflammatory (crystals present, a low or moderate cell count, a negative Gram stain, infection excluded): treat the specific cause — gout or CPPD → an NSAID, colchicine, or a glucocorticoid (see the crystal arthropathy approach); RA or other → flare management (see the relevant approach); reassess if not improving.

• When uncertain: treat empirically for septic arthritis until cultures and the clinical course exclude it — the cost of a missed septic joint (rapid cartilage destruction, sepsis) far exceeds brief empiric antibiotics.

• PT/OT: early mobilization after source control (septic disease); functional recovery; joint protection.

• Trend: synovial fluid results, the joint exam (pain, swelling, range of motion), CRP/ESR, blood cultures and clearance, the response to drainage and antibiotics (septic) or anti-inflammatory therapy (inflammatory), and systemic signs.

• Escalation triggers: septic arthritis → emergent orthopedic drainage and IV antibiotics with possible ICU; sepsis or septic shock → the sepsis pathway and ICU; prosthetic joint infection → ID and orthopedics (staged); failure to improve on inflammatory treatment → re-aspirate and re-evaluate for a missed infection; disseminated gonococcal disease → ID and ceftriaxone.

• Discharge checklist: the diagnosis established (septic versus inflammatory) with appropriate treatment underway; if septic: an antibiotic regimen and duration (ID-directed) with an IV-to-oral plan and source control done; if inflammatory: cause-specific therapy and follow-up; orthopedics, ID, and rheumatology follow-up as relevant; return precautions for a worsening joint, fever, spreading infection, inability to bear weight, or systemic symptoms.

Red Flags

• A hot joint treated as crystal or inflammatory without aspirating → a missed septic arthritis destroys the joint within days.

• Crystals seen, so infection "excluded" → they coexist; a high cell count or positive Gram stain still means infection.

• A synovial WBC above 50,000 with neutrophil predominance → presume septic and treat as an emergency.

• A prosthetic joint with an acute effusion → prosthetic joint infection; a distinct, often staged pathway.

• Migratory polyarthralgia, tenosynovitis, and pustular rash in a young patient → disseminated gonococcal infection.

Senior IM Resident Pearls

• Aspirate first. The synovial fluid answers the only question that matters — infection that eats the joint, or inflammation you can treat at leisure.

• Crystals don't exclude infection. The two coexist; a high cell count or positive Gram stain means a septic joint even with crystals present.

• When uncertain, treat the septic joint. Let cultures talk you out of it — two days of antibiotics for gout is trivial next to a missed septic joint.

• Source control is essential. Antibiotics alone don't cure a septic joint; it needs drainage or washout.

• The prosthetic joint runs its own track. Acute effusion in a replaced joint means prosthetic joint infection — ID and orthopedics, often staged.

• Think gonococcal in the young. Migratory arthralgia, tenosynovitis, and a pustular rash point to disseminated gonococcal disease.

• Common mistake: stopping the workup at "crystals seen" in a febrile patient — the cell count and Gram stain still have to exclude a coexisting infection.

Rheumatology — Inflammatory Arthritis

103. Rheumatoid Arthritis (RA) Flare

/RAFlare · polyarthritis · functional decline · medication-related issues · symmetric small-joint synovitis · bridge with steroids, optimize DMARDs/biologics, screen infection before escalating immunosuppression · Super Compact

Sx: increased symmetric polyarthritis — pain, swelling, prolonged morning stiffness (>1 h), warmth in small joints (MCPs, PIPs, wrists, MTPs); functional decline (grip, ambulation, ADLs); may have low-grade fever, fatigue; possible extra-articular activity (nodules, serositis, scleritis, ILD) · (before you escalate immunosuppression for a "flare," make sure it isn't an infection — a septic joint or systemic infection in an immunosuppressed RA patient can masquerade as a flare, and giving more immunosuppression would be exactly wrong)

Neg: denies infection masquerading as flare (septic joint, systemic infection — screen before escalating immunosuppression) · denies missed septic arthritis in a single disproportionately inflamed joint (aspirate) · denies medication nonadherence/lapse as the trigger · denies missed extra-articular/serious complication (ILD, vasculitis, cervical spine instability) · denies steroid-only management without DMARD optimization

SHx: RA duration + severity + erosions, current DMARDs/biologics + adherence, prior flares + triggers, recent infection/illness, steroid history, functional baseline, smoking, vaccination status, prior TB screening (for biologics)

Etiology: autoimmune synovial inflammation (pannus) driven by cytokines (TNF, IL-6) and autoantibodies (RF, anti-CCP); flares triggered by medication lapse/tapering, infection, stress, surgery, or inadequate disease control; functional decline from active synovitis ± joint damage

RF: established RA · medication nonadherence/taper · infection · recent surgery/stress · undertreated disease · smoking · seropositivity (RF/anti-CCP)

Data: CRP/ESR (activity), CBC, RF/anti-CCP (if not known), renal/hepatic function · joint exam + count; aspirate any disproportionately inflamed single joint to exclude septic arthritis; infection workup if febrile (cultures, CXR); imaging if erosive/complication suspected; TB/hepatitis screening before starting/escalating biologics; assess cervical spine (atlantoaxial instability) if intubation/surgery planned

DDx: RA flare · septic arthritis (superimposed) · crystal arthritis (coexisting gout/CPPD) · viral polyarthritis · other inflammatory arthritis (psoriatic, SLE) · medication-related (loss of efficacy) · osteoarthritis · paraneoplastic

Home Meds: continue methotrexate/DMARDs unless infection or contraindication; HOLD biologics/immunosuppressants if active infection suspected; reconcile; folic acid with methotrexate; screen TB/hepatitis before biologic initiation; consider stress-dose steroids if on chronic glucocorticoids and acutely ill

Plan

CONSULT: Rheumatology (flare management, DMARD/biologic optimization, diagnostic uncertainty) · Orthopedics (if septic joint suspected) · Infectious Disease (infection vs flare, biologic-related infection) · PT/OT (functional decline)

– FIRST screen for infection (the critical fork): if febrile or a single disproportionately inflamed joint → cultures + arthrocentesis to exclude septic arthritis before escalating immunosuppression (see the septic-vs-inflammatory arthritis approach)
– TREAT THE FLARE (once infection excluded/addressed):
  • Glucocorticoid bridge: prednisone (e.g. ~10–20 mg PO daily, flare-severity dependent) with a taper, OR intra-articular glucocorticoid for limited joints, OR a short methylprednisolone course for severe flares — per rheumatology
  • NSAID for symptom control if no contraindication (CKD/GI/CV)
  • Optimize/resume DMARD therapy: continue methotrexate (with folic acid) or other conventional DMARD; escalate/adjust biologic or targeted-synthetic DMARD (TNF inhibitor, IL-6 inhibitor, JAK inhibitor, etc.) per rheumatology — address the loss of disease control, not just the symptoms
– ADDRESS THE TRIGGER: restart lapsed medications, treat infection, manage perioperative state
– EVALUATE EXTRA-ARTICULAR/SERIOUS FEATURES: ILD, vasculitis, scleritis, cervical spine instability (esp before any airway management/surgery)
– The reflex when an RA patient flares is to give more immunosuppression, and the single most important discipline is to pause and make sure you're not feeding an infection. An immunosuppressed RA patient with a fever and swollen joints could be flaring — or could have a septic joint or a systemic infection that looks identical, and steroids or a biologic would be precisely the wrong move. So screen for infection first, aspirate any joint that's inflamed out of proportion to the rest, and only then treat the flare. The flare treatment itself is a two-part idea: a glucocorticoid bridge to calm the acute synovitis quickly, and — just as important — fixing the underlying loss of disease control by optimizing the DMARD or biologic, because steroids alone treat today's symptoms while the disease keeps damaging joints. And never forget the cervical spine: longstanding RA can cause atlantoaxial instability, which matters enormously the moment someone reaches for an airway.
– PT/OT: important — functional assessment, joint protection, assistive devices, hand therapy, mobility
– Trend: joint counts/pain/stiffness, CRP/ESR, functional status, infection markers, response to bridge + DMARD optimization, medication tolerability (LFTs, CBC)
– Escalation triggers: septic arthritis/systemic infection → hold immunosuppression + treat infection (orthopedics/ID); severe extra-articular disease (vasculitis, ILD flare) → urgent rheumatology ± ICU; cervical myelopathy/instability → urgent imaging + neurosurgery/spine; refractory flare → rheumatology escalation
– Discharge checklist: flare controlled + infection excluded/treated; steroid bridge with taper plan; DMARD/biologic regimen optimized + adherence addressed; folic acid with methotrexate; TB/hepatitis screening if new biologic; rheumatology follow-up (early); PT/OT arranged; vaccination plan; return precautions (fever, worsening/new single hot joint, functional decline, medication side effects, neuro symptoms — cervical spine)

103. Rheumatoid Arthritis (RA) Flare

/RAFlare · complete reference · symmetric polyarthritis + functional decline · screen infection before escalating immunosuppression, bridge with steroids, optimize the DMARD · Full Card

Symptoms / Associated Sx

• Increased symmetric polyarthritis — pain, swelling, prolonged morning stiffness (over 1 hour), and warmth in the small joints (MCPs, PIPs, wrists, MTPs)

• Functional decline (grip, ambulation, ADLs); a possible low-grade fever and fatigue; possible extra-articular activity (nodules, serositis, scleritis, ILD)

• Before escalating immunosuppression for a "flare," make sure it isn't an infection — a septic joint or systemic infection in an immunosuppressed RA patient can masquerade as a flare, and giving more immunosuppression would be exactly wrong

Neg

• Pt denies an infection masquerading as a flare (septic joint, systemic infection — screen before escalating immunosuppression) and a missed septic arthritis in a single disproportionately inflamed joint (aspirate).

• Pt denies medication nonadherence or a lapse as the trigger and a missed extra-articular or serious complication (ILD, vasculitis, cervical spine instability).

• Pt denies steroid-only management without DMARD optimization.

Social History (SHx)

• RA duration, severity, and erosions, and current DMARDs or biologics with adherence.

• Prior flares and triggers, recent infection or illness, and steroid history.

• Functional baseline, smoking, vaccination status, and prior TB screening (for biologics).

Main Etiology

• Autoimmune synovial inflammation (pannus) driven by cytokines (TNF, IL-6) and autoantibodies (rheumatoid factor, anti-CCP)

• Flares are triggered by a medication lapse or taper, infection, stress, surgery, or inadequate disease control

• Functional decline arises from active synovitis with or without joint damage

RF

• Modifiable: medication nonadherence or taper, infection, recent surgery or stress, undertreated disease, and smoking.

• Non-modifiable: established RA and seropositivity (rheumatoid factor, anti-CCP).

Data

• CRP/ESR (activity), CBC, rheumatoid factor and anti-CCP (if not known), and renal and hepatic function

• A joint exam and count; aspirate any disproportionately inflamed single joint to exclude septic arthritis; an infection workup if febrile (cultures, CXR)

• Imaging if erosive disease or a complication is suspected; TB and hepatitis screening before starting or escalating biologics; assess the cervical spine (atlantoaxial instability) if intubation or surgery is planned.

DDx

RA flare · septic arthritis (superimposed) · crystal arthritis (coexisting gout or CPPD) · viral polyarthritis · other inflammatory arthritis (psoriatic, SLE) · medication-related loss of efficacy · osteoarthritis · paraneoplastic arthritis

Home Meds

• Continue methotrexate and DMARDs unless there is infection or a contraindication; folic acid with methotrexate.

• Hold biologics and immunosuppressants if active infection is suspected; screen TB and hepatitis before biologic initiation.

• Consider stress-dose steroids if on chronic glucocorticoids and acutely ill; reconcile.

Plan

CONSULT: Rheumatology (flare management, DMARD/biologic optimization, diagnostic uncertainty) · Orthopedics (if a septic joint is suspected) · Infectious Disease (infection versus flare, biologic-related infection) · PT/OT (functional decline)

• First screen for infection (the critical fork): if febrile or with a single disproportionately inflamed joint → cultures and arthrocentesis to exclude septic arthritis before escalating immunosuppression (see the septic-versus-inflammatory arthritis approach).

• Treat the flare (once infection is excluded or addressed):

• • Glucocorticoid bridge: prednisone (e.g. ~10–20 mg PO daily, flare-severity dependent) with a taper, or an intra-articular glucocorticoid for limited joints, or a short methylprednisolone course for severe flares — per rheumatology.

• • NSAID for symptom control if there is no contraindication (CKD, GI, cardiovascular).

• • Optimize or resume DMARD therapy: continue methotrexate (with folic acid) or another conventional DMARD; escalate or adjust a biologic or targeted-synthetic DMARD (TNF inhibitor, IL-6 inhibitor, JAK inhibitor) per rheumatology — address the loss of disease control, not just the symptoms.

• Address the trigger: restart lapsed medications, treat infection, and manage the perioperative state.

• Evaluate extra-articular and serious features: ILD, vasculitis, scleritis, and cervical spine instability (especially before any airway management or surgery).

• PT/OT: important — functional assessment, joint protection, assistive devices, hand therapy, and mobility.

• Trend: joint counts, pain, and stiffness, CRP/ESR, functional status, infection markers, the response to the bridge and DMARD optimization, and medication tolerability (LFTs, CBC).

• Escalation triggers: septic arthritis or systemic infection → hold immunosuppression and treat the infection (orthopedics, ID); severe extra-articular disease (vasculitis, an ILD flare) → urgent rheumatology with possible ICU; cervical myelopathy or instability → urgent imaging and neurosurgery or spine; a refractory flare → rheumatology escalation.

• Discharge checklist: the flare controlled and infection excluded or treated; a steroid bridge with a taper plan; an optimized DMARD/biologic regimen with adherence addressed; folic acid with methotrexate; TB and hepatitis screening if a new biologic; early rheumatology follow-up; PT/OT arranged; a vaccination plan; return precautions for fever, a worsening or new single hot joint, functional decline, medication side effects, or neuro symptoms (cervical spine).

Red Flags

• Fever with swollen joints in an immunosuppressed RA patient → screen for infection before adding immunosuppression.

• A single joint inflamed out of proportion → aspirate to exclude a superimposed septic arthritis.

• Neck pain with neuro symptoms in longstanding RA → atlantoaxial instability; image before any airway manipulation.

• New dyspnea or cough → an RA-associated ILD flare; don't attribute it to the joints alone.

• Steroid-only management → treats symptoms while the disease keeps damaging joints; optimize the DMARD.

Senior IM Resident Pearls

• Pause before adding immunosuppression. A flare and an infection look identical in an immunosuppressed RA patient — screen first.

• Aspirate the out-of-proportion joint. A superimposed septic arthritis hides among the flaring joints.

• The flare is two problems. A glucocorticoid bridge calms the synovitis; optimizing the DMARD fixes the loss of disease control.

• Steroids alone aren't enough. They treat today's symptoms while the disease keeps eroding joints — address the underlying control.

• Remember the cervical spine. Longstanding RA causes atlantoaxial instability that matters the moment someone reaches for an airway.

• Screen before biologics. TB and hepatitis reactivation are real risks — screen before starting or escalating.

• Common mistake: reflexively bumping the steroids for a "flare" in a febrile patient without aspirating the worst joint or screening for infection.

Rheumatology — Inflammatory

104. Polymyalgia Rheumatica (PMR)

/PMR · shoulder + hip girdle pain and morning stiffness · elevated ESR/CRP in an older adult · dramatic response to low-dose steroids · always screen for GCA overlap · Super Compact

Sx: bilateral shoulder and/or hip girdle pain + prolonged morning stiffness (>45 min) in an adult ≥50, often abrupt; difficulty rising from a chair, raising arms, dressing; constitutional symptoms (fatigue, low-grade fever, weight loss); NO true muscle weakness (pain limits, strength preserved) · (every PMR patient must be screened for giant cell arteritis, because the two overlap and missing GCA risks permanent blindness — ask specifically about headache, scalp tenderness, jaw claudication, and visual symptoms at every visit)

Neg: denies GCA features missed (headache, jaw claudication, visual symptoms, scalp tenderness — would change management dramatically) · denies true weakness (suggests inflammatory myopathy — check CK) · denies RA (small-joint synovitis, RF/anti-CCP) · denies missed malignancy/infection mimicking · denies starting high-dose steroids (PMR responds to LOW dose — a high-dose requirement suggests GCA or another diagnosis)

SHx: age ≥50 (rare younger), symptom onset/duration, GCA symptom screen, functional impact, prior steroid use, comorbidities affecting steroids (diabetes, osteoporosis, glaucoma), polymyalgia vs myopathy history

Etiology: inflammatory condition of unknown cause affecting periarticular structures (bursae, tendons) of the shoulder and hip girdles; shares pathophysiology and frequently overlaps with giant cell arteritis (large-vessel vasculitis); strongly age-associated

RF: age ≥50 · female · northern European ancestry · association with GCA

Data: elevated ESR and/or CRP (hallmark — usually markedly elevated), CBC (anemia of inflammation), NORMAL creatine kinase (CK) — distinguishes from myopathy, RF/anti-CCP (exclude RA), TSH; screen for GCA clinically (and temporal artery biopsy/imaging if GCA features present); consider imaging (US/MRI — bursitis) if diagnosis unclear; rule out infection/malignancy if atypical

DDx: PMR · giant cell arteritis (overlap) · RA (elderly-onset) · inflammatory myopathy (elevated CK, true weakness) · hypothyroidism · fibromyalgia · osteoarthritis · malignancy/paraneoplastic · infection · statin myopathy

Home Meds: reconcile; review statins (myalgia mimic); plan steroid-sparing bone/GI/glucose protection (calcium/vitamin D, bisphosphonate per risk, PPI if indicated, glucose monitoring); avoid starting steroids before excluding GCA features that would require higher dosing

Plan

CONSULT: Rheumatology (diagnosis confirmation, steroid taper, atypical/refractory, GCA concern) · Ophthalmology (urgent if any visual symptoms — GCA) · PT (functional)

– SCREEN FOR GCA FIRST (the critical step): ask about headache, jaw claudication, visual symptoms, scalp tenderness; if GCA features present → treat as GCA with HIGH-dose steroids urgently (see the giant cell arteritis approach), do not treat as isolated PMR
– TREAT PMR (no GCA features): low-dose glucocorticoid — prednisone 15–20 mg PO daily; expect a dramatic response within days (a hallmark — lack of rapid response should prompt reconsideration of the diagnosis)
– TAPER slowly over months once symptoms and inflammatory markers normalize (guided by clinical response + ESR/CRP); typical course 1–2+ years; relapses common with rapid taper
– STEROID-SPARING / complication prevention: calcium + vitamin D, bone protection (bisphosphonate per fracture risk — steroid-induced osteoporosis), glucose monitoring, GI protection if indicated; methotrexate as a steroid-sparing agent for relapsing/steroid-dependent disease per rheumatology
– REASSESS the diagnosis if: poor steroid response, high-dose requirement, true weakness/elevated CK, atypical features (→ consider myopathy, RA, malignancy, infection)
– PMR is one of the most satisfying diagnoses to treat — an older patient who can barely lift their arms or rise from a chair, with a sky-high ESR and a normal CK, who feels transformed within forty-eight hours of a modest dose of prednisone. That dramatic, low-dose response is both the treatment and a diagnostic test: if 15–20 mg doesn't produce a near-miraculous improvement in a few days, the diagnosis is probably wrong. But the reason PMR earns real vigilance is its shadow, giant cell arteritis — the two are the same disease spectrum, and a meaningful fraction of PMR patients have or develop GCA, which can blind them permanently and which needs high-dose steroids, not low. So you screen for GCA at every encounter, asking specifically about headache, jaw claudication, scalp tenderness, and any visual symptom, and the moment those appear you stop thinking "PMR" and treat for GCA. The other discipline is mundane but matters: these patients are on steroids for a year or more, so protect their bones, their glucose, and their stomach from the start.
– PT/OT: gentle mobility, function as pain improves; fall prevention
– Trend: symptom response (rapid is expected), ESR/CRP normalization, taper tolerance/relapse, steroid complications (glucose, BP, bone, mood), emergence of GCA features
– Escalation triggers: any visual symptom or GCA feature → urgent high-dose steroids + ophthalmology (see GCA approach); poor steroid response → reconsider diagnosis (myopathy, malignancy); relapsing/steroid-dependent → methotrexate + rheumatology; steroid complications → manage/adjust
– Discharge checklist: diagnosis confirmed + GCA excluded; prednisone 15–20 mg with a slow taper plan; bone/glucose/GI protection started; rheumatology follow-up; explicit patient education on GCA warning symptoms (headache, jaw claudication, visual changes) → seek care urgently; return precautions (visual symptoms, severe headache, poor response, steroid side effects)

104. Polymyalgia Rheumatica (PMR)

/PMR · complete reference · girdle pain + stiffness + high ESR/CRP in the older adult · dramatic low-dose steroid response, always screen for GCA · Full Card

Symptoms / Associated Sx

• Bilateral shoulder and/or hip girdle pain with prolonged morning stiffness (over 45 minutes) in an adult 50 or older, often abrupt in onset

• Difficulty rising from a chair, raising the arms, and dressing; constitutional symptoms (fatigue, low-grade fever, weight loss); no true muscle weakness (pain limits movement, but strength is preserved)

• Every PMR patient must be screened for giant cell arteritis, because the two overlap and missing GCA risks permanent blindness — ask specifically about headache, scalp tenderness, jaw claudication, and visual symptoms at every visit

Neg

• Pt denies missed GCA features (headache, jaw claudication, visual symptoms, scalp tenderness — which would change management dramatically) and true weakness (which suggests an inflammatory myopathy — check CK).

• Pt denies RA (small-joint synovitis, rheumatoid factor and anti-CCP) and a missed malignancy or infection mimicking it.

• Pt denies starting high-dose steroids (PMR responds to low dose — a high-dose requirement suggests GCA or another diagnosis).

Social History (SHx)

• Age 50 or older (rare younger), symptom onset and duration, and a GCA symptom screen.

• Functional impact and prior steroid use.

• Comorbidities affecting steroid use (diabetes, osteoporosis, glaucoma) and a polymyalgia-versus-myopathy history.

Main Etiology

• An inflammatory condition of unknown cause affecting the periarticular structures (bursae, tendons) of the shoulder and hip girdles

• It shares pathophysiology and frequently overlaps with giant cell arteritis (a large-vessel vasculitis)

• It is strongly age-associated

RF

• Non-modifiable: age 50 or older, female sex, northern European ancestry, and an association with GCA.

Data

• An elevated ESR and/or CRP (the hallmark — usually markedly elevated), CBC (anemia of inflammation)

• A normal creatine kinase (CK) — which distinguishes it from a myopathy, rheumatoid factor and anti-CCP (to exclude RA), and TSH

• Screen for GCA clinically (and a temporal artery biopsy or imaging if GCA features are present); consider imaging (ultrasound or MRI — bursitis) if the diagnosis is unclear; rule out infection or malignancy if atypical.

DDx

PMR · giant cell arteritis (overlap) · elderly-onset RA · inflammatory myopathy (elevated CK, true weakness) · hypothyroidism · fibromyalgia · osteoarthritis · malignancy or paraneoplastic syndrome · infection · statin myopathy

Home Meds

• Reconcile medications; review statins (a myalgia mimic).

• Plan steroid-sparing bone, GI, and glucose protection (calcium and vitamin D, a bisphosphonate per risk, a PPI if indicated, glucose monitoring).

• Avoid starting steroids before excluding GCA features that would require higher dosing.

Plan

CONSULT: Rheumatology (diagnosis confirmation, steroid taper, atypical or refractory disease, GCA concern) · Ophthalmology (urgent if any visual symptoms — GCA) · PT (functional impairment)

• Screen for GCA first (the critical step): ask about headache, jaw claudication, visual symptoms, and scalp tenderness; if GCA features are present → treat as GCA with high-dose steroids urgently (see the giant cell arteritis approach), do not treat as isolated PMR.

• Treat PMR (no GCA features): a low-dose glucocorticoid — prednisone 15–20 mg PO daily; expect a dramatic response within days (a hallmark — a lack of rapid response should prompt reconsideration of the diagnosis).

• Taper slowly over months once symptoms and inflammatory markers normalize (guided by the clinical response and ESR/CRP); the typical course is 1–2 or more years; relapses are common with a rapid taper.

• Steroid-sparing and complication prevention: calcium and vitamin D, bone protection (a bisphosphonate per fracture risk — steroid-induced osteoporosis), glucose monitoring, and GI protection if indicated; methotrexate as a steroid-sparing agent for relapsing or steroid-dependent disease per rheumatology.

• Reassess the diagnosis if: there is a poor steroid response, a high-dose requirement, true weakness or an elevated CK, or atypical features (→ consider myopathy, RA, malignancy, infection).

• PT/OT: gentle mobility, function as pain improves, and fall prevention.

• Trend: the symptom response (rapid is expected), ESR/CRP normalization, taper tolerance and relapse, steroid complications (glucose, BP, bone, mood), and the emergence of GCA features.

• Escalation triggers: any visual symptom or GCA feature → urgent high-dose steroids and ophthalmology (see the GCA approach); a poor steroid response → reconsider the diagnosis (myopathy, malignancy); relapsing or steroid-dependent disease → methotrexate and rheumatology; steroid complications → manage and adjust.

• Discharge checklist: the diagnosis confirmed and GCA excluded; prednisone 15–20 mg with a slow taper plan; bone, glucose, and GI protection started; rheumatology follow-up; explicit patient education on GCA warning symptoms (headache, jaw claudication, visual changes) → seek care urgently; return precautions for visual symptoms, severe headache, a poor response, or steroid side effects.

Red Flags

• Headache, jaw claudication, scalp tenderness, or any visual symptom → giant cell arteritis; treat with high-dose steroids urgently, not low-dose.

• A poor or absent response to 15–20 mg prednisone → the diagnosis is probably wrong; reconsider.

• True muscle weakness with an elevated CK → an inflammatory myopathy, not PMR.

• A high-dose steroid requirement → suggests GCA or an alternative diagnosis.

• Atypical features (young age, focal findings, weight loss) → exclude malignancy and infection.

Senior IM Resident Pearls

• The low-dose response is diagnostic. A near-miraculous improvement within days on 15–20 mg prednisone supports PMR; its absence argues against it.

• GCA is PMR's dangerous shadow. The two are one spectrum — screen for headache, jaw claudication, scalp tenderness, and visual symptoms every time.

• The moment GCA features appear, change gears. Stop thinking low-dose PMR and treat for GCA with high-dose steroids to save vision.

• A normal CK separates PMR from myopathy. Pain limits movement in PMR, but true weakness with a high CK is a different disease.

• Protect against steroids from day one. These patients are on prednisone for a year or more — bones, glucose, and stomach.

• Taper slowly. Relapses are common with rapid tapers; follow symptoms and inflammatory markers down.

• Common mistake: treating PMR and forgetting to educate the patient about the GCA symptoms that should send them in immediately — the blindness is preventable.

Rheumatology — Vasculitis EMERGENCY

105. Giant Cell Arteritis (GCA)

/GCA · headache · jaw claudication · vision symptoms · scalp tenderness · a MEDICAL EMERGENCY — start high-dose steroids IMMEDIATELY to prevent blindness, do NOT wait for biopsy · Super Compact

Sx: adult ≥50 with new headache (often temporal), jaw claudication (highly specific), scalp tenderness, visual symptoms (amaurosis fugax, diplopia, vision loss), constitutional symptoms (fever, weight loss, fatigue); PMR overlap (girdle pain/stiffness); tender/thickened/pulseless temporal artery · (this is an ophthalmologic emergency — irreversible blindness can occur suddenly from anterior ischemic optic neuropathy, and the single decision that saves vision is to start high-dose steroids the moment GCA is suspected, BEFORE the temporal artery biopsy, because the biopsy stays positive for days after steroids begin)

Neg: denies delaying steroids for biopsy (start immediately — vision loss is irreversible; biopsy remains positive for ~1–2 weeks on steroids) · denies missed visual symptoms / impending vision loss (requires IV pulse steroids) · denies missed jaw claudication (specific) · denies missed large-vessel involvement (aortitis/aneurysm, limb claudication) · denies missing PMR overlap · denies stopping steroids prematurely (relapse)

SHx: age ≥50, headache/visual/jaw symptom timeline, PMR history, prior GCA, vision baseline, comorbidities affecting steroids, cardiovascular disease (large-vessel risk)

Etiology: granulomatous large- and medium-vessel vasculitis affecting the aorta and its branches, especially the extracranial branches of the carotid (temporal, ophthalmic arteries); inflammation → luminal narrowing → ischemia (optic nerve → blindness, jaw muscles → claudication); strongly age-associated, overlaps with PMR

RF: age ≥50 (peak 70s) · female · northern European ancestry · PMR · >50 the dominant risk

Data: markedly elevated ESR and/or CRP (hallmark — but normal markers don't fully exclude), CBC (anemia, thrombocytosis); temporal artery biopsy is the diagnostic gold standard (but DO NOT delay steroids for it — biopsy remains positive days after starting); temporal/axillary artery ultrasound (halo sign) and large-vessel imaging (CTA/MRA/PET for aortitis) increasingly used; ophthalmology evaluation if visual symptoms

DDx: GCA · other causes of headache (tension, migraine, secondary) · non-arteritic anterior ischemic optic neuropathy · other vasculitis · PMR (overlap) · infection · malignancy · TMJ disorder (jaw pain mimic)

Home Meds: start high-dose glucocorticoid IMMEDIATELY; add low-dose aspirin (may reduce ischemic events) unless contraindicated; bone/GI/glucose protection (calcium/vitamin D, bisphosphonate, PPI if indicated, glucose monitoring) given prolonged high-dose steroids; reconcile

Plan

CONSULT: Rheumatology (URGENT — diagnosis, steroid/tocilizumab management, taper) · Ophthalmology (EMERGENT if any visual symptoms) · Surgery/Pathology (temporal artery biopsy) · Vascular (large-vessel involvement)

– START STEROIDS IMMEDIATELY — the moment GCA is suspected, do NOT wait for biopsy or imaging:
  • NO visual symptoms: prednisone 40–60 mg PO daily (high-dose)
  • VISUAL symptoms / vision loss / impending blindness: IV methylprednisolone 500–1000 mg daily for 3 days, then high-dose oral prednisone — to prevent fellow-eye involvement and salvage vision
– ARRANGE temporal artery biopsy (gold standard) promptly — but it does NOT delay treatment (remains positive for ~1–2 weeks on steroids); consider temporal/axillary ultrasound (halo sign) and large-vessel imaging (aortitis)
– ADD low-dose aspirin 81 mg daily (reduces ischemic complications) unless contraindicated
– TOCILIZUMAB (IL-6 inhibitor) as a steroid-sparing agent (GiACTA trial — improves sustained remission and reduces cumulative steroid exposure) per rheumatology, especially for relapsing/steroid-dependent disease or to limit steroid toxicity
– STEROID COMPLICATION PREVENTION: calcium + vitamin D, bisphosphonate (steroid osteoporosis), glucose monitoring, GI protection, BP; very slow taper over many months–1+ year guided by symptoms + ESR/CRP; monitor for relapse
– MONITOR for large-vessel complications: aortic aneurysm/dissection surveillance, limb claudication
– Giant cell arteritis is the rheumatologic emergency where hesitation costs eyesight. An older patient with a new headache, jaw claudication, and a high ESR who mentions even a flicker of visual change is at risk of sudden, permanent, irreversible blindness from optic nerve ischemia — and the fellow eye can follow within days. The single decision that defines good care is to start high-dose steroids the instant you suspect GCA, before the temporal artery biopsy, because the biopsy stays positive for one to two weeks after steroids begin, so you lose nothing diagnostically by treating first and you may save the patient's vision. If there are visual symptoms or vision loss, you escalate to IV pulse methylprednisolone, not oral. The biopsy and the ultrasound confirm the diagnosis on their own schedule; tocilizumab has earned a role as a steroid-sparing agent to limit the brutal toll of a year or more of high-dose steroids. And because that toll is real, you protect the bones, glucose, and stomach from day one and add aspirin to reduce ischemic events.
– PT/OT: as needed; fall prevention on steroids
– Trend: visual status (urgent), headache/jaw symptoms, ESR/CRP, steroid response + complications (glucose, BP, bone, mood), biopsy/imaging results, relapse on taper, large-vessel surveillance
– Escalation triggers: any visual symptom/vision loss → IV pulse methylprednisolone + EMERGENT ophthalmology; suspected aortic dissection/aneurysm → urgent imaging + vascular/surgery; relapse on taper → increase steroids + tocilizumab + rheumatology; steroid complications → manage
– Discharge checklist: diagnosis pursued (biopsy/imaging) + treatment started without delay; high-dose prednisone with a long slow taper plan; aspirin; bone/glucose/GI protection; tocilizumab plan if indicated; rheumatology (urgent) + ophthalmology follow-up; aortic surveillance plan; patient educated that any visual change = emergency; return precautions (visual symptoms, severe headache, jaw/tongue claudication, limb symptoms, steroid side effects)

105. Giant Cell Arteritis (GCA)

/GCA · complete reference · headache + jaw claudication + visual symptoms in the older adult · start high-dose steroids immediately (IV pulse if visual), biopsy does not delay treatment · Full Card

Symptoms / Associated Sx

• An adult 50 or older with a new headache (often temporal), jaw claudication (highly specific), scalp tenderness, visual symptoms (amaurosis fugax, diplopia, vision loss), and constitutional symptoms (fever, weight loss, fatigue)

• PMR overlap (girdle pain and stiffness); a tender, thickened, or pulseless temporal artery

• This is an ophthalmologic emergency — irreversible blindness can occur suddenly from anterior ischemic optic neuropathy, and the single decision that saves vision is to start high-dose steroids the moment GCA is suspected, before the temporal artery biopsy, because the biopsy stays positive for days after steroids begin

Neg

• Pt denies delaying steroids for the biopsy (start immediately — vision loss is irreversible; the biopsy remains positive for ~1–2 weeks on steroids) and missed visual symptoms or impending vision loss (which require IV pulse steroids).

• Pt denies missed jaw claudication (specific) and missed large-vessel involvement (aortitis or aneurysm, limb claudication).

• Pt denies missing a PMR overlap and stopping steroids prematurely (relapse).

Social History (SHx)

• Age 50 or older, and the headache, visual, and jaw symptom timeline.

• PMR history, prior GCA, and the vision baseline.

• Comorbidities affecting steroid use and cardiovascular disease (large-vessel risk).

Main Etiology

• A granulomatous large- and medium-vessel vasculitis affecting the aorta and its branches, especially the extracranial branches of the carotid (the temporal and ophthalmic arteries)

• Inflammation causes luminal narrowing and ischemia (the optic nerve → blindness, the jaw muscles → claudication)

• It is strongly age-associated and overlaps with PMR

RF

• Non-modifiable: age 50 or older (peak in the 70s), female sex, northern European ancestry, and PMR; age over 50 is the dominant risk.

Data

• A markedly elevated ESR and/or CRP (the hallmark — but normal markers don't fully exclude it), CBC (anemia, thrombocytosis)

• A temporal artery biopsy is the diagnostic gold standard (but do not delay steroids for it — the biopsy remains positive days after starting); temporal and axillary artery ultrasound (the halo sign) and large-vessel imaging (CTA, MRA, or PET for aortitis) are increasingly used

• An ophthalmology evaluation if there are visual symptoms.

DDx

GCA · other causes of headache (tension, migraine, secondary) · non-arteritic anterior ischemic optic neuropathy · other vasculitis · PMR (overlap) · infection · malignancy · TMJ disorder (a jaw pain mimic)

Home Meds

• Start a high-dose glucocorticoid immediately.

• Add low-dose aspirin (may reduce ischemic events) unless contraindicated.

• Begin bone, GI, and glucose protection (calcium and vitamin D, a bisphosphonate, a PPI if indicated, glucose monitoring) given the prolonged high-dose steroids; reconcile.

Plan

CONSULT: Rheumatology (urgent — diagnosis, steroid and tocilizumab management, taper) · Ophthalmology (emergent if any visual symptoms) · Surgery/Pathology (temporal artery biopsy) · Vascular (large-vessel involvement)

• Start steroids immediately — the moment GCA is suspected, do not wait for the biopsy or imaging:

• • No visual symptoms: prednisone 40–60 mg PO daily (high-dose).

• • Visual symptoms, vision loss, or impending blindness: IV methylprednisolone 500–1000 mg daily for 3 days, then high-dose oral prednisone — to prevent fellow-eye involvement and salvage vision.

• Arrange a temporal artery biopsy (gold standard) promptly — but it does not delay treatment (it remains positive for ~1–2 weeks on steroids); consider temporal and axillary ultrasound (the halo sign) and large-vessel imaging (aortitis).

• Add low-dose aspirin 81 mg daily (reduces ischemic complications) unless contraindicated.

• Tocilizumab (an IL-6 inhibitor) as a steroid-sparing agent (the GiACTA trial — improving sustained remission and reducing cumulative steroid exposure) per rheumatology, especially for relapsing or steroid-dependent disease or to limit steroid toxicity.

• Steroid complication prevention: calcium and vitamin D, a bisphosphonate (steroid osteoporosis), glucose monitoring, GI protection, and BP control; a very slow taper over many months to over a year guided by symptoms and ESR/CRP; monitor for relapse.

• Monitor for large-vessel complications: aortic aneurysm or dissection surveillance, and limb claudication.

• PT/OT: as needed; fall prevention on steroids.

• Trend: visual status (urgent), headache and jaw symptoms, ESR/CRP, the steroid response and complications (glucose, BP, bone, mood), biopsy and imaging results, relapse on taper, and large-vessel surveillance.

• Escalation triggers: any visual symptom or vision loss → IV pulse methylprednisolone and emergent ophthalmology; suspected aortic dissection or aneurysm → urgent imaging and vascular or surgery; relapse on taper → increase steroids, tocilizumab, and rheumatology; steroid complications → manage.

• Discharge checklist: the diagnosis pursued (biopsy, imaging) with treatment started without delay; high-dose prednisone with a long slow taper plan; aspirin; bone, glucose, and GI protection; a tocilizumab plan if indicated; urgent rheumatology and ophthalmology follow-up; an aortic surveillance plan; the patient educated that any visual change is an emergency; return precautions for visual symptoms, severe headache, jaw or tongue claudication, limb symptoms, or steroid side effects.

Red Flags

• Any visual symptom or vision loss → impending irreversible blindness; IV pulse methylprednisolone and emergent ophthalmology.

• Delaying steroids for the biopsy → vision can be lost in the interim; treat first, biopsy stays positive for 1–2 weeks.

• Jaw claudication → highly specific for GCA; treat as the emergency it signals.

• New limb claudication or asymmetric pulses → large-vessel involvement; image the aorta.

• Relapse during the taper → increase steroids and consider tocilizumab; don't taper on a fixed schedule alone.

Senior IM Resident Pearls

• Treat first, biopsy later. Start high-dose steroids the instant you suspect GCA — the biopsy stays positive for 1–2 weeks, so you lose nothing by treating.

• Visual symptoms mean IV pulse. Vision loss or amaurosis escalates from oral prednisone to IV methylprednisolone to save the eye and protect its fellow.

• Jaw claudication is the specific clue. Few things cause it — its presence should move GCA to the top.

• Normal inflammatory markers don't fully exclude it. Most have a high ESR/CRP, but clinical suspicion still drives treatment.

• Tocilizumab spares steroids. GiACTA showed better sustained remission and less cumulative steroid — valuable given the year-plus course.

• Watch the aorta. GCA is a large-vessel vasculitis — aneurysm and dissection are late complications worth surveilling.

• Common mistake: sending the patient for a biopsy before starting steroids — the delay is exactly when the vision is lost, and it gains nothing.

Rheumatology — Autoimmune

106. Systemic Lupus Erythematosus (SLE) Flare

/SLEFlare · arthritis · serositis · cytopenias · lupus nephritis · check complement + dsDNA + organ involvement, treat by severity/organ, screen infection · Super Compact

Sx: multi-system flare — arthritis (symmetric, non-erosive), mucocutaneous (malar/discoid rash, oral ulcers, photosensitivity, alopecia), serositis (pleuritis, pericarditis), cytopenias (anemia, leukopenia, thrombocytopenia), renal (lupus nephritis — proteinuria, active sediment), neuropsychiatric, constitutional (fever, fatigue); severity ranges from mild (skin/joints) to organ-threatening · (the central inpatient question in a febrile lupus patient is flare versus infection — they look alike, and immunosuppressed lupus patients get serious infections, so you must work both up in parallel rather than reflexively escalating immunosuppression)

Neg: denies infection mistaken for flare (immunosuppressed — fever could be sepsis; work up both) · denies missed major-organ involvement (nephritis, CNS, severe cytopenias, cardiopulmonary — changes management) · denies missed lupus nephritis (check urine/protein) · denies missed antiphospholipid syndrome/thrombosis · denies stopping hydroxychloroquine (protective — should continue) · denies missed TTP/MAHA (overlap)

SHx: SLE duration + organ involvement history, current immunosuppression + adherence, prior flares + severity, antiphospholipid status, renal history, infection/vaccination history, pregnancy, medication triggers, sun exposure

Etiology: autoimmune multi-system disease with immune-complex deposition + autoantibodies (ANA, anti-dsDNA, anti-Smith) → inflammation across organs; flares triggered by infection, UV exposure, medication nonadherence (esp stopping hydroxychloroquine), pregnancy, stress; complement consumption marks activity

RF: female (reproductive age) · African/Hispanic/Asian ancestry · established SLE · medication nonadherence · UV exposure · infection

Data: complement (C3/C4 — LOW with activity), anti-dsDNA (rising titer tracks activity), CBC (cytopenias), CRP/ESR (ESR up; CRP often near-normal in flare — high CRP suggests infection), renal: urinalysis with microscopy (active sediment, casts), urine protein/creatinine ratio, creatinine; antiphospholipid antibodies; infection workup (cultures, imaging) — parallel to flare workup; organ-specific testing (echo, imaging, LP if neuropsychiatric); peripheral smear (exclude TTP/MAHA)

DDx: SLE flare · infection (mimics flare) · drug-induced lupus · lupus nephritis (organ-specific) · antiphospholipid syndrome/thrombosis · TTP/MAHA (overlap) · other connective tissue disease · medication toxicity

Home Meds: CONTINUE hydroxychloroquine (protective, reduces flares — do not stop); continue/adjust immunosuppression per severity; HOLD/adjust immunosuppression if serious infection; reconcile; stress-dose steroids if chronically on steroids + acutely ill; review lupus-triggering drugs

Plan

CONSULT: Rheumatology (flare severity assessment, immunosuppression) · Nephrology (lupus nephritis — see the lupus nephritis approach) · Infectious Disease (infection vs flare) · relevant organ specialists (cardiology, neurology, hematology) · ICU if organ/life-threatening

– FIRST work up infection in parallel (the key fork): cultures + imaging if febrile; do not reflexively escalate immunosuppression until infection is reasonably excluded or treated (high CRP, focal signs favor infection)
– ASSESS SEVERITY + ORGAN INVOLVEMENT (drives therapy): check complement, dsDNA, CBC, renal (urinalysis/protein), and organ-specific evaluation
– TREAT BY SEVERITY/ORGAN:
  • Mild (skin/joints/serositis): continue hydroxychloroquine; NSAIDs; low-dose prednisone (e.g. ≤20 mg) short course; topical therapy for skin
  • Moderate: moderate-dose glucocorticoids + steroid-sparing immunosuppressant (e.g. methotrexate, azathioprine) per rheumatology
  • Severe / major-organ (nephritis, CNS, severe cytopenias, cardiopulmonary): high-dose glucocorticoids (± IV methylprednisolone pulse) + potent immunosuppression — mycophenolate mofetil or cyclophosphamide per rheumatology; lupus nephritis → see the dedicated lupus nephritis approach (biopsy-driven induction)
– ALWAYS continue hydroxychloroquine (reduces flares, improves outcomes) unless a specific contraindication
– ADDRESS TRIGGERS: treat infection, restart lapsed meds, sun protection
– SCREEN for antiphospholipid syndrome/thrombosis and TTP/MAHA (smear) if features present
– A lupus flare in the hospital is dominated by one fork in the road: is this the disease or an infection? They present almost identically — fever, malaise, cytopenias — and the patient is immunosuppressed, so a serious infection is both more likely and more dangerous, which means you work both up at once rather than reflexively reaching for more steroids. A couple of cheap clues help: in a true flare the complement falls and the anti-dsDNA rises while the CRP often stays surprisingly low, whereas a high CRP and focal findings point toward infection. Once you've sorted that, the treatment is entirely driven by severity and which organ is involved — mild skin-and-joint disease gets hydroxychloroquine and a little prednisone, while major-organ disease like lupus nephritis or CNS involvement gets high-dose steroids plus mycophenolate or cyclophosphamide. The one drug you almost never stop is hydroxychloroquine: it reduces flares and improves survival, and stopping it is itself a common flare trigger.
– PT/OT: per functional impact
– Trend: complement (rising = improving), dsDNA, CBC, renal (protein/sediment/creatinine), organ-specific markers, infection workup, response to therapy, steroid complications
– Escalation triggers: major-organ/life-threatening flare (nephritis, CNS, severe cytopenias, cardiopulmonary) → high-dose steroids + potent immunosuppression + relevant specialist ± ICU; serious infection → hold immunosuppression + treat; TTP/MAHA → plasma exchange + hematology; antiphospholipid thrombosis → anticoagulation
– Discharge checklist: flare controlled + infection excluded/treated + organ involvement characterized; hydroxychloroquine continued; immunosuppression regimen per severity with taper; bone/GI/glucose protection if steroids; rheumatology (+ nephrology if renal) follow-up; sun protection + adherence counseling; vaccination plan; return precautions (fever, worsening organ symptoms, new neuro/renal/cardiopulmonary signs, medication effects)

106. Systemic Lupus Erythematosus (SLE) Flare

/SLEFlare · complete reference · multi-system flare · work up infection in parallel, assess organ involvement, treat by severity, never stop hydroxychloroquine · Full Card

Symptoms / Associated Sx

• A multi-system flare — arthritis (symmetric, non-erosive), mucocutaneous disease (malar or discoid rash, oral ulcers, photosensitivity, alopecia), serositis (pleuritis, pericarditis), cytopenias (anemia, leukopenia, thrombocytopenia), renal disease (lupus nephritis — proteinuria, active sediment), neuropsychiatric disease, and constitutional symptoms (fever, fatigue)

• Severity ranges from mild (skin and joints) to organ-threatening

• The central inpatient question in a febrile lupus patient is flare versus infection — they look alike, and immunosuppressed lupus patients get serious infections, so you must work both up in parallel rather than reflexively escalating immunosuppression

Neg

• Pt denies an infection mistaken for a flare (immunosuppressed — fever could be sepsis; work up both) and missed major-organ involvement (nephritis, CNS, severe cytopenias, cardiopulmonary disease — which changes management).

• Pt denies missed lupus nephritis (check the urine and protein) and missed antiphospholipid syndrome or thrombosis.

• Pt denies stopping hydroxychloroquine (protective — should continue) and missed TTP or MAHA (overlap).

Social History (SHx)

• SLE duration and organ involvement history, and current immunosuppression with adherence.

• Prior flares and severity, antiphospholipid status, and renal history.

• Infection and vaccination history, pregnancy, medication triggers, and sun exposure.

Main Etiology

• An autoimmune multi-system disease with immune-complex deposition and autoantibodies (ANA, anti-dsDNA, anti-Smith) causing inflammation across organs

• Flares are triggered by infection, UV exposure, medication nonadherence (especially stopping hydroxychloroquine), pregnancy, and stress

• Complement consumption marks activity

RF

• Modifiable: medication nonadherence, UV exposure, and infection.

• Non-modifiable: female sex (reproductive age), African, Hispanic, or Asian ancestry, and established SLE.

Data

• Complement (C3/C4 — low with activity), anti-dsDNA (a rising titer tracks activity), and CBC (cytopenias)

• CRP/ESR (the ESR rises; the CRP is often near-normal in a flare — a high CRP suggests infection)

• Renal: urinalysis with microscopy (active sediment, casts), a urine protein-to-creatinine ratio, and creatinine

• Antiphospholipid antibodies; an infection workup (cultures, imaging) in parallel to the flare workup; organ-specific testing (echo, imaging, LP if neuropsychiatric); a peripheral smear (to exclude TTP/MAHA).

DDx

SLE flare · infection (mimics a flare) · drug-induced lupus · lupus nephritis (organ-specific) · antiphospholipid syndrome or thrombosis · TTP or MAHA (overlap) · other connective tissue disease · medication toxicity

Home Meds

• Continue hydroxychloroquine (protective, reduces flares — do not stop).

• Continue or adjust immunosuppression per severity; hold or adjust it if there is a serious infection.

• Consider stress-dose steroids if chronically on steroids and acutely ill; review lupus-triggering drugs; reconcile.

Plan

CONSULT: Rheumatology (flare severity assessment, immunosuppression) · Nephrology (lupus nephritis — see the lupus nephritis approach) · Infectious Disease (infection versus flare) · relevant organ specialists (cardiology, neurology, hematology) · ICU if organ- or life-threatening

• First work up infection in parallel (the key fork): cultures and imaging if febrile; do not reflexively escalate immunosuppression until infection is reasonably excluded or treated (a high CRP and focal signs favor infection).

• Assess severity and organ involvement (drives therapy): check complement, dsDNA, CBC, renal status (urinalysis, protein), and organ-specific evaluation.

• Treat by severity and organ:

• • Mild (skin, joints, serositis): continue hydroxychloroquine; NSAIDs; a short course of low-dose prednisone (e.g. ≤20 mg); topical therapy for skin.

• • Moderate: moderate-dose glucocorticoids with a steroid-sparing immunosuppressant (e.g. methotrexate, azathioprine) per rheumatology.

• • Severe or major-organ (nephritis, CNS, severe cytopenias, cardiopulmonary): high-dose glucocorticoids (with possible IV methylprednisolone pulse) and potent immunosuppression — mycophenolate mofetil or cyclophosphamide per rheumatology; lupus nephritis → see the dedicated lupus nephritis approach (biopsy-driven induction).

• Always continue hydroxychloroquine (reduces flares, improves outcomes) unless there is a specific contraindication.

• Address triggers: treat infection, restart lapsed medications, and ensure sun protection.

• Screen for antiphospholipid syndrome or thrombosis and TTP/MAHA (smear) if features are present.

• PT/OT: per functional impact.

• Trend: complement (rising = improving), dsDNA, CBC, renal status (protein, sediment, creatinine), organ-specific markers, the infection workup, the response to therapy, and steroid complications.

• Escalation triggers: a major-organ or life-threatening flare (nephritis, CNS, severe cytopenias, cardiopulmonary disease) → high-dose steroids, potent immunosuppression, the relevant specialist, and possible ICU; a serious infection → hold immunosuppression and treat; TTP/MAHA → plasma exchange and hematology; antiphospholipid thrombosis → anticoagulation.

• Discharge checklist: the flare controlled, infection excluded or treated, and organ involvement characterized; hydroxychloroquine continued; an immunosuppression regimen per severity with a taper; bone, GI, and glucose protection if steroids; rheumatology (and nephrology if renal) follow-up; sun protection and adherence counseling; a vaccination plan; return precautions for fever, worsening organ symptoms, new neuro, renal, or cardiopulmonary signs, or medication effects.

Red Flags

• Fever in an immunosuppressed lupus patient → could be sepsis, not a flare; work up infection in parallel.

• A high CRP (versus the usually-modest CRP of a flare) → favors infection over disease activity.

• Active urine sediment with proteinuria → lupus nephritis; pursue the renal pathway (often biopsy).

• Schistocytes with thrombocytopenia → TTP/MAHA overlap; an emergency needing plasma exchange.

• Stopping hydroxychloroquine → itself a flare trigger and a loss of survival benefit; continue it.

Senior IM Resident Pearls

• Flare or infection is the fork. They look identical, the patient is immunosuppressed, so work both up at once rather than escalating immunosuppression on reflex.

• Complement and dsDNA track activity. In a true flare complement falls and dsDNA rises — while the CRP often stays surprisingly low.

• A high CRP points away from a flare. Lupus activity tends to spare the CRP, so a high one nudges you toward infection.

• Treatment follows the organ. Skin and joints get hydroxychloroquine and a little prednisone; nephritis and CNS disease get high-dose steroids plus mycophenolate or cyclophosphamide.

• Almost never stop hydroxychloroquine. It reduces flares and improves survival, and stopping it is a common trigger.

• Always check the kidneys. Lupus nephritis can be silent — a urinalysis and protein quantification belong in every flare workup.

• Common mistake: escalating immunosuppression for a presumed flare in a febrile patient before excluding the infection that the immunosuppression would worsen.

Rheumatology — Vasculitis

107. Vasculitis Workup

/VasculitisWorkup · ANCA-associated vasculitis (GPA, MPA, EGPA) + small-vessel disease · differentiate by vessel size + ANCA + organ pattern, then induce remission · treat pulmonary-renal disease as urgent · Super Compact

Approach — DIFFERENTIATE by vessel size + ANCA pattern + organ involvement. Vasculitis is inflammation of vessel walls causing ischemia; the workup classifies by vessel size (large/medium/small) and, for the small-vessel ANCA-associated group, by the ANCA pattern (c-ANCA/PR3 vs p-ANCA/MPO) and the organ footprint. The job is to recognize it, classify it, and induce remission before irreversible organ damage — especially in pulmonary-renal disease.

Sx: constitutional (fever, weight loss, fatigue) + organ-specific — GPA (sinusitis, nasal crusting/saddle nose, hemoptysis/pulmonary nodules, glomerulonephritis) · MPA (rapidly progressive glomerulonephritis, pulmonary hemorrhage, neuropathy) · EGPA (asthma, eosinophilia, neuropathy, sinusitis) · small-vessel skin (palpable purpura), mononeuritis multiplex, pulmonary-renal syndrome · (the combination that demands urgency is pulmonary-renal — hemoptysis or hypoxia with a rising creatinine and active urine sediment is alveolar hemorrhage plus rapidly progressive glomerulonephritis, an organ-and-life-threatening emergency that needs immediate immunosuppression and sometimes plasma exchange)

Neg: denies missed pulmonary-renal syndrome / RPGN (alveolar hemorrhage + rapidly rising creatinine — emergency) · denies missed infection/malignancy mimicking vasculitis (exclude before immunosuppressing) · denies missing mononeuritis multiplex (specific) · denies delayed biopsy/treatment in organ-threatening disease · denies missing drug-induced/cocaine-levamisole vasculitis · denies missing the EGPA asthma/eosinophilia pattern

SHx: symptom timeline + organ pattern, ENT/sinus disease, asthma/allergy (EGPA), prior vasculitis, infections (hepatitis — cryoglobulinemic), drug/cocaine use, smoking, renal history

Etiology: immune-mediated vessel-wall inflammation; ANCA-associated (GPA, MPA, EGPA) small-vessel vasculitis with pauci-immune injury; classified by vessel size (large — GCA/Takayasu; medium — PAN; small — ANCA-associated, immune-complex/cryoglobulinemic, IgA); organ damage from ischemia/necrosis

RF: varies by type · ANCA-associated (older adults) · infections (hepatitis → cryoglobulinemic) · drugs (hydralazine, cocaine-levamisole, PTU) · genetic

Data: ANCA testing (c-ANCA/anti-PR3 → GPA; p-ANCA/anti-MPO → MPA, EGPA), urinalysis with microscopy (active sediment/casts → glomerulonephritis), creatinine, CBC (eosinophilia → EGPA), CRP/ESR · chest imaging (nodules, hemorrhage, infiltrates), CT sinuses; complement, cryoglobulins, hepatitis serologies (immune-complex types); TISSUE BIOPSY (kidney, skin, lung, nerve) confirms + classifies; exclude infection/malignancy/endocarditis (mimics)

DDx: GPA · MPA · EGPA · other small-vessel (IgA, cryoglobulinemic) · medium-vessel (PAN) · large-vessel (GCA, Takayasu) · infection/endocarditis (mimic) · malignancy · drug-induced vasculitis · antiphospholipid/thrombotic mimics

Home Meds: reconcile; review vasculitis-inducing drugs (hydralazine, PTU, cocaine); plan immunosuppression + infection prophylaxis (PJP prophylaxis with high-dose steroids/cyclophosphamide/rituximab); bone/GI/glucose protection for steroids

Plan

CONSULT: Rheumatology (diagnosis, classification, induction therapy) · Nephrology (glomerulonephritis/RPGN — urgent if rising creatinine) · Pulmonology (alveolar hemorrhage) · relevant biopsy service (renal/ENT/derm) · ICU if pulmonary-renal/organ-threatening

– RECOGNIZE + STRATIFY URGENCY FIRST: pulmonary-renal syndrome (alveolar hemorrhage + RPGN), rapidly rising creatinine, or organ-threatening disease → EMERGENCY, treat immediately; otherwise complete classification then treat
– EXCLUDE MIMICS: infection (including endocarditis), malignancy — before/alongside committing to immunosuppression
– CLASSIFY: ANCA pattern + organ involvement + biopsy (kidney/skin/lung/nerve) to confirm and subtype (GPA vs MPA vs EGPA vs other)
– INDUCTION (organ/life-threatening ANCA-associated vasculitis):
  • High-dose glucocorticoids (IV methylprednisolone pulse 500–1000 mg/day ×3 for severe, then high-dose oral prednisone)
  • PLUS rituximab OR cyclophosphamide (RAVE — rituximab non-inferior/preferred for relapsing or fertility concerns; RITUXVAS) per rheumatology
  • PLASMA EXCHANGE in select severe disease (severe alveolar hemorrhage, severe RPGN/dialysis-dependent, anti-GBM overlap) per nephrology/rheumatology
– NON-SEVERE disease: glucocorticoids + rituximab or methotrexate/mycophenolate per rheumatology
– EGPA: glucocorticoids ± immunosuppression; mepolizumab (IL-5 inhibitor) for eosinophilic disease per rheumatology
– PROPHYLAXIS: PJP prophylaxis, bone/GI/glucose protection, vaccination, infection monitoring during immunosuppression
– MAINTENANCE: rituximab or azathioprine after induction; long-term rheumatology follow-up; monitor relapse (ANCA, organ markers)
– A vasculitis workup is a classification exercise with an emergency hiding inside it. You sort by vessel size and, for the ANCA-associated small-vessel group, by the ANCA pattern and the organ footprint: c-ANCA against PR3 leans GPA with its sinus disease and saddle nose, p-ANCA against MPO leans MPA, and asthma with eosinophilia points to EGPA. But before you settle into careful subtyping, scan for the one combination that won't wait — pulmonary-renal syndrome, where alveolar hemorrhage and a rapidly climbing creatinine with an active urinary sediment mean the lungs and kidneys are being destroyed in real time. That picture earns immediate high-dose steroids plus rituximab or cyclophosphamide, and plasma exchange in the most severe cases. The other discipline is to exclude the mimics — infection, especially endocarditis, and malignancy — because vasculitis treatment is heavy immunosuppression, and giving it to someone with sepsis masquerading as vasculitis is a disaster. RAVE established rituximab as a mainstay; whatever the agent, remember PJP prophylaxis.
– PT/OT: per organ involvement/neuropathy/deconditioning
– Trend: renal function + urine sediment, oxygenation/hemoptysis (alveolar hemorrhage), ANCA titer, CRP/ESR, organ-specific markers, response to induction, infection during immunosuppression
– Escalation triggers: pulmonary-renal syndrome / alveolar hemorrhage / RPGN → ICU + urgent immunosuppression ± plasma exchange + nephrology/pulmonology; respiratory failure → ICU; rapidly rising creatinine → urgent nephrology/dialysis; serious infection on immunosuppression → treat + adjust
– Discharge checklist: diagnosis confirmed/classified + mimics excluded + induction underway; immunosuppression regimen (steroids + rituximab/cyclophosphamide) + maintenance plan; PJP + bone/GI/glucose prophylaxis; rheumatology + organ-specialist follow-up; relapse monitoring plan; return precautions (hemoptysis, dyspnea, decreased urine/edema, fever/infection, neuro symptoms)

107. Vasculitis Workup

/VasculitisWorkup · complete reference · classify by vessel size + ANCA + organ pattern, exclude mimics, treat pulmonary-renal disease as an emergency, induce remission · Full Card

Approach — Differentiate by Vessel Size, ANCA Pattern, and Organ Involvement

• Vasculitis is inflammation of vessel walls causing ischemia; the workup classifies by vessel size (large, medium, small) and, for the small-vessel ANCA-associated group, by the ANCA pattern (c-ANCA/PR3 versus p-ANCA/MPO) and the organ footprint. The job is to recognize it, classify it, and induce remission before irreversible organ damage — especially in pulmonary-renal disease.

• GPA: sinusitis, nasal crusting or saddle nose, hemoptysis or pulmonary nodules, and glomerulonephritis (c-ANCA/PR3).

• MPA: rapidly progressive glomerulonephritis, pulmonary hemorrhage, and neuropathy (p-ANCA/MPO).

• EGPA: asthma, eosinophilia, neuropathy, and sinusitis.

• The combination that demands urgency is pulmonary-renal — hemoptysis or hypoxia with a rising creatinine and active urine sediment is alveolar hemorrhage plus rapidly progressive glomerulonephritis, an organ-and-life-threatening emergency that needs immediate immunosuppression and sometimes plasma exchange.

Neg

• Pt denies a missed pulmonary-renal syndrome or RPGN (alveolar hemorrhage with a rapidly rising creatinine — an emergency) and a missed infection or malignancy mimicking vasculitis (exclude before immunosuppressing).

• Pt denies missing mononeuritis multiplex (specific) and a delayed biopsy or treatment in organ-threatening disease.

• Pt denies missing drug-induced or cocaine-levamisole vasculitis and missing the EGPA asthma and eosinophilia pattern.

Social History (SHx)

• The symptom timeline and organ pattern, ENT and sinus disease, and asthma or allergy (EGPA).

• Prior vasculitis and infections (hepatitis — cryoglobulinemic disease).

• Drug or cocaine use, smoking, and renal history.

Main Etiology

• Immune-mediated vessel-wall inflammation; the ANCA-associated group (GPA, MPA, EGPA) is a small-vessel vasculitis with pauci-immune injury

• Classified by vessel size (large — GCA, Takayasu; medium — PAN; small — ANCA-associated, immune-complex or cryoglobulinemic, IgA)

• Organ damage arises from ischemia and necrosis

RF

• Modifiable: infections (hepatitis → cryoglobulinemic disease) and drugs (hydralazine, cocaine-levamisole, PTU).

• Non-modifiable: ANCA-associated disease in older adults and genetic predisposition.

Data

• ANCA testing (c-ANCA/anti-PR3 → GPA; p-ANCA/anti-MPO → MPA, EGPA), urinalysis with microscopy (active sediment or casts → glomerulonephritis), creatinine, CBC (eosinophilia → EGPA), and CRP/ESR

• Chest imaging (nodules, hemorrhage, infiltrates) and a CT of the sinuses

• Complement, cryoglobulins, and hepatitis serologies (immune-complex types)

• A tissue biopsy (kidney, skin, lung, nerve) confirms and classifies; exclude infection, malignancy, and endocarditis (mimics).

DDx

GPA · MPA · EGPA · other small-vessel disease (IgA, cryoglobulinemic) · medium-vessel disease (PAN) · large-vessel disease (GCA, Takayasu) · infection or endocarditis (a mimic) · malignancy · drug-induced vasculitis · antiphospholipid or thrombotic mimics

Home Meds

• Reconcile medications; review vasculitis-inducing drugs (hydralazine, PTU, cocaine).

• Plan immunosuppression with infection prophylaxis (PJP prophylaxis with high-dose steroids, cyclophosphamide, or rituximab).

• Begin bone, GI, and glucose protection for steroids.

Plan

CONSULT: Rheumatology (diagnosis, classification, induction therapy) · Nephrology (glomerulonephritis or RPGN — urgent if a rising creatinine) · Pulmonology (alveolar hemorrhage) · the relevant biopsy service (renal, ENT, derm) · ICU if pulmonary-renal or organ-threatening disease

• Recognize and stratify urgency first: pulmonary-renal syndrome (alveolar hemorrhage with RPGN), a rapidly rising creatinine, or organ-threatening disease → an emergency, treat immediately; otherwise complete classification then treat.

• Exclude mimics: infection (including endocarditis) and malignancy — before or alongside committing to immunosuppression.

• Classify: the ANCA pattern, organ involvement, and a biopsy (kidney, skin, lung, nerve) to confirm and subtype (GPA versus MPA versus EGPA versus other).

• Induction (organ- or life-threatening ANCA-associated vasculitis):

• • High-dose glucocorticoids (IV methylprednisolone pulse 500–1000 mg/day for 3 days in severe disease, then high-dose oral prednisone).

• • Plus rituximab or cyclophosphamide (RAVE — rituximab non-inferior and preferred for relapsing disease or fertility concerns; RITUXVAS) per rheumatology.

• • Plasma exchange in select severe disease (severe alveolar hemorrhage, severe RPGN or dialysis-dependence, anti-GBM overlap) per nephrology and rheumatology.

• Non-severe disease: glucocorticoids with rituximab or methotrexate or mycophenolate per rheumatology.

• EGPA: glucocorticoids with possible immunosuppression; mepolizumab (an IL-5 inhibitor) for eosinophilic disease per rheumatology.

• Prophylaxis: PJP prophylaxis, bone, GI, and glucose protection, vaccination, and infection monitoring during immunosuppression.

• Maintenance: rituximab or azathioprine after induction; long-term rheumatology follow-up; monitor relapse (ANCA, organ markers).

• PT/OT: per organ involvement, neuropathy, or deconditioning.

• Trend: renal function and urine sediment, oxygenation and hemoptysis (alveolar hemorrhage), the ANCA titer, CRP/ESR, organ-specific markers, the response to induction, and infection during immunosuppression.

• Escalation triggers: pulmonary-renal syndrome, alveolar hemorrhage, or RPGN → ICU, urgent immunosuppression with possible plasma exchange, and nephrology and pulmonology; respiratory failure → ICU; a rapidly rising creatinine → urgent nephrology and dialysis; a serious infection on immunosuppression → treat and adjust.

• Discharge checklist: the diagnosis confirmed and classified, mimics excluded, and induction underway; an immunosuppression regimen (steroids with rituximab or cyclophosphamide) and a maintenance plan; PJP and bone, GI, and glucose prophylaxis; rheumatology and organ-specialist follow-up; a relapse monitoring plan; return precautions for hemoptysis, dyspnea, decreased urine or edema, fever or infection, or neuro symptoms.

Red Flags

• Hemoptysis or hypoxia with a rising creatinine and active sediment → pulmonary-renal syndrome; an emergency.

• A rapidly rising creatinine with an active urinary sediment → rapidly progressive glomerulonephritis; urgent immunosuppression.

• Fever and a vasculitic picture → exclude endocarditis and infection before immunosuppressing.

• Asthma, eosinophilia, and neuropathy → EGPA; consider an IL-5 inhibitor.

• Mononeuritis multiplex → a specific vasculitic finding; pursue the workup and biopsy.

Senior IM Resident Pearls

• Classify by vessel size, ANCA, and organ footprint. PR3/c-ANCA leans GPA, MPO/p-ANCA leans MPA, asthma with eosinophilia points to EGPA.

• Scan for pulmonary-renal first. Alveolar hemorrhage with a climbing creatinine destroys lungs and kidneys in real time — it won't wait for subtyping.

• Exclude the mimics. Endocarditis and malignancy can imitate vasculitis, and the treatment is heavy immunosuppression.

• RAVE put rituximab front and center. It's non-inferior to cyclophosphamide and preferred for relapsing disease or fertility concerns.

• Plasma exchange for the worst. Severe alveolar hemorrhage, severe RPGN, and anti-GBM overlap are where it earns its place.

• Don't forget PJP prophylaxis. High-dose steroids with cyclophosphamide or rituximab demand it.

• Common mistake: immunosuppressing a febrile "vasculitis" before excluding endocarditis — the mimic that punishes the missed diagnosis severely.

Rheumatology — Crystal Arthritis

108. Crystal Arthropathy Workup

/CrystalArthropathyWorkup · gout vs CPPD (pseudogout) · the crystal under polarized light decides · exclude septic joint, treat the flare, address CPPD secondary causes · Super Compact

Approach — DIFFERENTIATE the crystal: gout vs CPPD. Both cause acute inflammatory monoarthritis that's clinically indistinguishable at the bedside; synovial fluid under polarized light tells them apart — gout: negatively birefringent NEEDLE-shaped monosodium urate crystals; CPPD/pseudogout: positively birefringent RHOMBOID-shaped calcium pyrophosphate crystals. As always, the same aspiration must exclude infection.

Sx: acute, painful, red, swollen, warm joint(s); gout classically first MTP/foot/ankle/knee; CPPD/pseudogout classically knee/wrist (also shoulder), often in older adults; both can mimic septic arthritis (fever, high inflammatory markers); chronic forms (tophaceous gout, CPPD-associated OA) · (at the bedside gout and pseudogout look the same — the only reliable way to tell them apart, and to exclude the septic joint that mimics both, is to aspirate the joint and examine the fluid, so the polarized-light crystal analysis is the heart of this workup)

Neg: denies missed septic arthritis (the same aspirate must exclude infection — crystals don't rule it out) · denies assuming gout without confirming the crystal type (treatment overlaps but the diagnosis/secondary workup differs) · denies missing CPPD secondary causes (hyperparathyroidism, hemochromatosis, hypomagnesemia, hypophosphatasia) · denies starting/stopping urate-lowering mid-flare in gout · denies NSAID use in CKD/CHF

SHx: prior flares + pattern + joints, urate-lowering therapy (gout), age (CPPD older), metabolic/endocrine disease (CPPD secondary causes), CKD, diuretics, alcohol, family history, prior chondrocalcinosis on imaging

Etiology: gout — monosodium urate crystal deposition from hyperuricemia → NLRP3 inflammasome/IL-1β inflammation · CPPD — calcium pyrophosphate dihydrate crystal deposition in cartilage (chondrocalcinosis) → acute "pseudogout" flares; CPPD often idiopathic/age-related but can be secondary to metabolic disease

RF: gout — hyperuricemia, CKD, diuretics, alcohol, metabolic syndrome · CPPD — older age, osteoarthritis, hyperparathyroidism, hemochromatosis, hypomagnesemia, hypophosphatasia, prior joint trauma

Data: ARTHROCENTESIS with polarized-light crystal analysis is definitive: gout = negatively birefringent needles (yellow when parallel); CPPD = positively birefringent rhomboids (blue when parallel) — PLUS cell count + Gram stain + culture to exclude infection · serum urate (gout, may be normal in flare), imaging: chondrocalcinosis on X-ray (CPPD); if CPPD: screen secondary causes — calcium/PTH (hyperparathyroidism), iron studies/ferritin (hemochromatosis), magnesium, phosphate/alkaline phosphatase; CRP/ESR, renal function (drug choice)

DDx: gout · CPPD/pseudogout · septic arthritis (must exclude) · other inflammatory arthritis (RA, psoriatic, reactive) · osteoarthritis flare · hemarthrosis · cellulitis · basic calcium phosphate disease

Home Meds: gout: continue urate-lowering if already on it, don't start/stop mid-flare; review diuretics; CPPD: address secondary cause + replete magnesium if low; renally dose flare meds; reconcile

Plan

CONSULT: Rheumatology (diagnostic uncertainty, refractory, CPPD secondary workup, urate-lowering) · Orthopedics (if septic joint) · Endocrinology (hyperparathyroidism) if CPPD secondary cause identified

– STEP 1 — ARTHROCENTESIS: crystal analysis + cell count + Gram stain + culture; exclude septic arthritis first (see the septic-vs-inflammatory arthritis approach — crystals do not rule out infection)
– STEP 2 — IDENTIFY THE CRYSTAL: negatively birefringent needles → gout; positively birefringent rhomboids → CPPD
– TREAT THE ACUTE FLARE (similar for both — choose by comorbidity):
  • NSAID (naproxen 500 mg PO BID or indomethacin) if no CKD/CHF/GI contraindication
  • Colchicine (1.2 mg then 0.6 mg 1 h later, then 0.6 mg daily–BID; renally adjust) — effective in both gout and CPPD
  • Glucocorticoid (prednisone 30–40 mg taper, or intra-articular triamcinolone after infection excluded) — preferred in CKD/CHF
  • IL-1 inhibitor (anakinra) for refractory cases per rheumatology
– GOUT-SPECIFIC (longer-term): continue existing urate-lowering through the flare; do NOT start it acutely; after resolution start urate-lowering (allopurinol/febuxostat) to target urate <6 (<5 if tophi) with flare prophylaxis (see the gout approach)
– CPPD-SPECIFIC: screen + treat secondary causes — hyperparathyroidism (calcium/PTH), hemochromatosis (iron studies), hypomagnesemia (replete magnesium), hypophosphatasia; no urate-lowering equivalent — management is flare treatment + addressing secondary causes + recurrence prophylaxis (low-dose colchicine) if frequent
– Gout and pseudogout are the same story told by two different crystals, and the bedside cannot reliably tell them apart — both produce a hot, swollen, agonizing joint that can look exactly like infection. The whole workup therefore hinges on the aspiration and the polarized-light microscope: negatively birefringent needles are urate and mean gout; positively birefringent rhomboids are calcium pyrophosphate and mean CPPD; and the same fluid's cell count and Gram stain are what keep you from missing the septic joint that imitates both. The acute treatment is largely shared — NSAIDs, colchicine, or steroids chosen by the patient's comorbidities — but the diagnoses diverge afterward. Gout has a long-term urate-lowering pathway with its own rules about not starting or stopping therapy mid-flare. CPPD has no urate equivalent; instead, when you find it, you go looking for a secondary cause — hyperparathyroidism, hemochromatosis, low magnesium, hypophosphatasia — because treating those changes the disease, and a young patient with CPPD especially deserves that search.
– PT/OT: joint rest acutely then mobilization
– Trend: joint exam, crystal/culture results, CRP/ESR, renal function (dosing), response to therapy, urate (gout), secondary-cause labs (CPPD)
– Escalation triggers: septic arthritis confirmed/suspected → orthopedics + drainage + antibiotics; refractory flare → IL-1 inhibitor + rheumatology; CPPD secondary cause found → treat it (endocrinology for hyperparathyroidism); systemic illness → reconsider infection
– Discharge checklist: crystal identified + infection excluded + flare controlled; gout: urate-lowering plan to target <6 with prophylaxis; CPPD: secondary-cause workup + treat + recurrence prophylaxis if frequent; rheumatology follow-up; return precautions (recurrent flare, fever + hot joint, medication effects)

108. Crystal Arthropathy Workup

/CrystalArthropathyWorkup · complete reference · gout vs CPPD on polarized light, exclude the septic joint, treat the flare, hunt CPPD secondary causes · Full Card

Approach — Differentiate the Crystal: Gout vs CPPD

• Both cause an acute inflammatory monoarthritis that's clinically indistinguishable at the bedside; synovial fluid under polarized light tells them apart — gout: negatively birefringent needle-shaped monosodium urate crystals; CPPD or pseudogout: positively birefringent rhomboid-shaped calcium pyrophosphate crystals.

• Gout is classically the first MTP, foot, ankle, or knee; CPPD is classically the knee, wrist, or shoulder, often in older adults.

• Both can mimic septic arthritis (fever, high inflammatory markers), and there are chronic forms (tophaceous gout, CPPD-associated osteoarthritis).

• At the bedside gout and pseudogout look the same — the only reliable way to tell them apart, and to exclude the septic joint that mimics both, is to aspirate the joint and examine the fluid, so the polarized-light crystal analysis is the heart of this workup.

Neg

• Pt denies a missed septic arthritis (the same aspirate must exclude infection — crystals don't rule it out) and assuming gout without confirming the crystal type (the treatment overlaps but the diagnosis and secondary workup differ).

• Pt denies missing CPPD secondary causes (hyperparathyroidism, hemochromatosis, hypomagnesemia, hypophosphatasia) and starting or stopping urate-lowering therapy mid-flare in gout.

• Pt denies NSAID use in CKD or CHF.

Social History (SHx)

• Prior flares with their pattern and joints, and urate-lowering therapy (gout).

• Age (CPPD is older), metabolic or endocrine disease (CPPD secondary causes), CKD, diuretics, and alcohol.

• Family history and prior chondrocalcinosis on imaging.

Main Etiology

• Gout — monosodium urate crystal deposition from hyperuricemia triggering NLRP3 inflammasome and IL-1β inflammation.

• CPPD — calcium pyrophosphate dihydrate crystal deposition in cartilage (chondrocalcinosis) causing acute "pseudogout" flares.

• CPPD is often idiopathic or age-related but can be secondary to metabolic disease.

RF

• Gout: hyperuricemia, CKD, diuretics, alcohol, and metabolic syndrome.

• CPPD: older age, osteoarthritis, hyperparathyroidism, hemochromatosis, hypomagnesemia, hypophosphatasia, and prior joint trauma.

Data

• Arthrocentesis with polarized-light crystal analysis is definitive: gout = negatively birefringent needles (yellow when parallel to the axis); CPPD = positively birefringent rhomboids (blue when parallel) — plus a cell count, Gram stain, and culture to exclude infection

• Serum urate (gout, may be normal in a flare); imaging: chondrocalcinosis on X-ray (CPPD)

• If CPPD: screen secondary causes — calcium and PTH (hyperparathyroidism), iron studies and ferritin (hemochromatosis), magnesium, and phosphate and alkaline phosphatase (hypophosphatasia)

• CRP/ESR and renal function (drug choice).

DDx

Gout · CPPD or pseudogout · septic arthritis (must exclude) · other inflammatory arthritis (RA, psoriatic, reactive) · an osteoarthritis flare · hemarthrosis · cellulitis · basic calcium phosphate disease

Home Meds

• Gout: continue urate-lowering therapy if already on it, don't start or stop it mid-flare; review diuretics.

• CPPD: address the secondary cause and replete magnesium if low.

• Renally dose flare medications; reconcile.

Plan

CONSULT: Rheumatology (diagnostic uncertainty, refractory disease, CPPD secondary workup, urate-lowering) · Orthopedics (if a septic joint) · Endocrinology (hyperparathyroidism) if a CPPD secondary cause is identified

• Step 1 — arthrocentesis: crystal analysis, cell count, Gram stain, and culture; exclude septic arthritis first (see the septic-versus-inflammatory arthritis approach — crystals do not rule out infection).

• Step 2 — identify the crystal: negatively birefringent needles → gout; positively birefringent rhomboids → CPPD.

• Treat the acute flare (similar for both — choose by comorbidity):

• • NSAID (naproxen 500 mg PO BID or indomethacin) if there is no CKD, CHF, or GI contraindication.

• • Colchicine (1.2 mg then 0.6 mg 1 hour later, then 0.6 mg daily to BID; renally adjust) — effective in both gout and CPPD.

• • Glucocorticoid (prednisone 30–40 mg with a taper, or intra-articular triamcinolone after infection is excluded) — preferred in CKD or CHF.

• • IL-1 inhibitor (anakinra) for refractory cases per rheumatology.

• Gout-specific (longer-term): continue existing urate-lowering therapy through the flare; do not start it acutely; after resolution start urate-lowering (allopurinol, febuxostat) to a target urate below 6 (below 5 if tophi) with flare prophylaxis (see the gout approach).

• CPPD-specific: screen and treat secondary causes — hyperparathyroidism (calcium, PTH), hemochromatosis (iron studies), hypomagnesemia (replete magnesium), hypophosphatasia; there is no urate-lowering equivalent — management is flare treatment plus addressing secondary causes plus recurrence prophylaxis (low-dose colchicine) if frequent.

• PT/OT: joint rest acutely then mobilization.

• Trend: the joint exam, crystal and culture results, CRP/ESR, renal function (dosing), the response to therapy, urate (gout), and secondary-cause labs (CPPD).

• Escalation triggers: septic arthritis confirmed or suspected → orthopedics, drainage, and antibiotics; a refractory flare → IL-1 inhibitor and rheumatology; a CPPD secondary cause found → treat it (endocrinology for hyperparathyroidism); systemic illness → reconsider infection.

• Discharge checklist: the crystal identified, infection excluded, and the flare controlled; gout: a urate-lowering plan to a target below 6 with prophylaxis; CPPD: a secondary-cause workup with treatment and recurrence prophylaxis if frequent; rheumatology follow-up; return precautions for a recurrent flare, fever with a hot joint, or medication effects.

Red Flags

• Fever with a hot joint → exclude septic arthritis with the same aspirate; crystals don't rule out infection.

• CPPD in a younger patient → hunt for a secondary cause (hyperparathyroidism, hemochromatosis, hypomagnesemia, hypophosphatasia).

• Assuming "gout" without crystal confirmation → the long-term management and secondary workup differ between gout and CPPD.

• Starting allopurinol during an acute gout flare → a urate shift that worsens it.

• NSAIDs or colchicine in significant CKD → toxicity; use glucocorticoids.

Senior IM Resident Pearls

• The microscope decides. Negatively birefringent needles are gout; positively birefringent rhomboids are CPPD — the bedside can't tell them apart.

• The same aspirate rules out infection. Cell count and Gram stain protect you from the septic joint that mimics both.

• The acute treatment is shared. NSAIDs, colchicine, or steroids chosen by comorbidity work for gout and pseudogout alike.

• The diagnoses diverge afterward. Gout has a urate-lowering pathway; CPPD does not — it has a secondary-cause hunt instead.

• Young CPPD earns a metabolic workup. Hemochromatosis and hyperparathyroidism especially can present this way.

• Check the magnesium in CPPD. Hypomagnesemia is a correctable contributor that's easy to overlook.

• Common mistake: labeling every acute monoarthritis "gout" without aspirating — missing both the CPPD secondary cause and the occasional septic joint.

Rheumatology — Renal

109. Lupus Nephritis

/LupusNephritis · AKI · proteinuria · active urine sediment in SLE · biopsy-driven class determines therapy · proliferative disease needs prompt induction immunosuppression · Super Compact

Sx: often clinically silent until advanced — detected on labs: proteinuria (may be nephrotic-range), active urine sediment (dysmorphic RBCs, RBC/cellular casts), rising creatinine/AKI, hypertension, edema; in a known or new SLE patient; may accompany systemic flare features · (lupus nephritis is frequently asymptomatic, so it must be actively sought with a urinalysis and protein quantification in every lupus patient — and the kidney biopsy is what determines the class, which in turn determines whether the patient needs aggressive induction immunosuppression or just supportive care)

Neg: denies untreated proliferative (class III/IV) nephritis (needs prompt induction — delay risks irreversible renal loss) · denies skipping the diagnostic biopsy (class drives therapy) · denies missed active sediment/proteinuria (silent disease) · denies infection before immunosuppression · denies TTP/MAHA or antiphospholipid-related renal disease · denies stopping hydroxychloroquine

SHx: SLE history + duration, prior nephritis + class + treatment, current immunosuppression, BP control, antiphospholipid status, infection/vaccination history, pregnancy plans (cyclophosphamide fertility), adherence

Etiology: immune-complex deposition in the glomerulus → inflammation/glomerulonephritis; classified I–VI by renal biopsy (ISN/RPS): I/II mesangial (mild), III/IV focal/diffuse proliferative (most aggressive, treat aggressively), V membranous (nephrotic), VI advanced sclerosis; class determines prognosis + therapy

RF: SLE (esp younger onset, African/Hispanic/Asian ancestry, male) · high disease activity · anti-dsDNA positivity · prior nephritis · nonadherence

Data: urinalysis with microscopy (active sediment, casts), urine protein quantification (protein/creatinine ratio or 24-h), creatinine/eGFR, complement (C3/C4 low), anti-dsDNA (high), CBC, albumin; RENAL BIOPSY is essential to determine class (III/IV/V) + activity/chronicity indices → guides therapy; antiphospholipid antibodies; exclude infection; BP assessment

DDx: lupus nephritis (by class) · other glomerulonephritis · antiphospholipid nephropathy/thrombotic microangiopathy · drug-induced (NSAID) · infection-related GN · diabetic/hypertensive nephropathy (comorbid) · acute tubular necrosis

Home Meds: CONTINUE hydroxychloroquine (renoprotective, improves outcomes); ACE inhibitor/ARB for proteinuria + BP; immunosuppression per class; hold/adjust if active infection; avoid nephrotoxins (NSAIDs); reconcile; bone/GI/glucose protection for steroids

Plan

CONSULT: Nephrology (essential — biopsy, induction/management, RPGN) · Rheumatology (immunosuppression, overall SLE) · ICU if RPGN/severe AKI/pulmonary-renal

– CONFIRM + CLASSIFY: renal biopsy to determine ISN/RPS class + activity/chronicity (drives whether aggressive induction is needed) — exclude infection and mimics first
– PROLIFERATIVE (CLASS III/IV) — prompt INDUCTION immunosuppression:
  • High-dose glucocorticoids (IV methylprednisolone pulse for severe, then oral prednisone taper)
  • PLUS mycophenolate mofetil OR cyclophosphamide (low-dose "Euro-Lupus" cyclophosphamide regimen — ELNT trial; or MMF, comparable efficacy with better tolerability) per nephrology/rheumatology
  • Consider add-on belimumab or voclosporin/calcineurin inhibitor (improve renal response per recent trials) per specialist
– MEMBRANOUS (CLASS V): RAAS blockade + immunosuppression (MMF/others) if significant proteinuria/nephrotic, per nephrology
– MILD (CLASS I/II): supportive + treat extrarenal SLE; usually no aggressive nephritis-specific immunosuppression
– SUPPORTIVE (all classes): ACE inhibitor or ARB for proteinuria + BP control (target per guidelines), continue hydroxychloroquine, manage edema/volume, statin/cardiovascular risk, avoid nephrotoxins
– MAINTENANCE after induction: mycophenolate or azathioprine for an extended period per specialist; monitor for relapse + drug toxicity; PJP prophylaxis with heavy immunosuppression
– Lupus nephritis is dangerous precisely because it's quiet — it can be silently destroying glomeruli while the patient feels fine, which is why a urinalysis with microscopy and a protein quantification belong in the evaluation of every lupus patient, looking for the active sediment and proteinuria that betray it. Once you suspect it, the kidney biopsy is not optional: the ISN/RPS class is what tells you whether you're dealing with mild mesangial disease that needs only supportive care, aggressive proliferative class III or IV disease that demands prompt induction immunosuppression to avoid irreversible renal loss, or membranous class V disease with its nephrotic physiology. The proliferative classes are where urgency lives — high-dose steroids plus either mycophenolate or low-dose Euro-Lupus cyclophosphamide, increasingly with an add-on like belimumab or voclosporin. And underneath all of it, two unglamorous measures matter for every class: an ACE inhibitor or ARB to cut proteinuria and control pressure, and hydroxychloroquine, which is genuinely renoprotective.
– PT/OT: per functional status
– Trend: creatinine/eGFR, proteinuria, urine sediment, complement (rising = improving), anti-dsDNA, BP, edema/volume, response to induction, infection/drug toxicity
– Escalation triggers: rapidly progressive glomerulonephritis (rapidly rising creatinine) → urgent nephrology + aggressive induction ± plasma exchange ± dialysis ± ICU; pulmonary-renal syndrome → ICU; nephrotic complications (thrombosis, severe edema) → manage; serious infection on immunosuppression → treat + adjust
– Discharge checklist: biopsy-confirmed class + induction underway (proliferative) or supportive plan (mild); immunosuppression + maintenance plan; ACE/ARB; hydroxychloroquine continued; BP target; PJP + bone/GI/glucose prophylaxis; nephrology + rheumatology follow-up; adherence + pregnancy counseling (cyclophosphamide); return precautions (decreased urine, worsening edema, rising weight, fever/infection, BP)

109. Lupus Nephritis

/LupusNephritis · complete reference · silent proteinuria + active sediment + AKI in SLE · biopsy determines class, proliferative disease needs prompt induction, ACE/ARB + hydroxychloroquine for all · Full Card

Symptoms / Associated Sx

• Often clinically silent until advanced — detected on labs: proteinuria (may be nephrotic-range), active urine sediment (dysmorphic RBCs, RBC or cellular casts), a rising creatinine or AKI, hypertension, and edema

• In a known or new SLE patient; it may accompany systemic flare features

• Lupus nephritis is frequently asymptomatic, so it must be actively sought with a urinalysis and protein quantification in every lupus patient — and the kidney biopsy is what determines the class, which in turn determines whether the patient needs aggressive induction immunosuppression or just supportive care

Neg

• Pt denies untreated proliferative (class III/IV) nephritis (needs prompt induction — delay risks irreversible renal loss) and skipping the diagnostic biopsy (class drives therapy).

• Pt denies a missed active sediment or proteinuria (silent disease) and infection before immunosuppression.

• Pt denies TTP/MAHA or antiphospholipid-related renal disease and stopping hydroxychloroquine.

Social History (SHx)

• SLE history and duration, and prior nephritis with its class and treatment.

• Current immunosuppression, BP control, and antiphospholipid status.

• Infection and vaccination history, pregnancy plans (cyclophosphamide and fertility), and adherence.

Main Etiology

• Immune-complex deposition in the glomerulus causing inflammation and glomerulonephritis

• Classified I–VI by renal biopsy (ISN/RPS): I/II mesangial (mild), III/IV focal or diffuse proliferative (the most aggressive, treated aggressively), V membranous (nephrotic), VI advanced sclerosis

• The class determines prognosis and therapy

RF

• Modifiable: high disease activity and nonadherence.

• Non-modifiable: SLE (especially younger onset, African, Hispanic, or Asian ancestry, male sex), anti-dsDNA positivity, and prior nephritis.

Data

• Urinalysis with microscopy (active sediment, casts), urine protein quantification (a protein-to-creatinine ratio or 24-hour collection), creatinine and eGFR, complement (C3/C4 low), and anti-dsDNA (high), CBC, albumin

• A renal biopsy is essential to determine the class (III/IV/V) and the activity and chronicity indices → which guides therapy

• Antiphospholipid antibodies; exclude infection; a BP assessment.

DDx

Lupus nephritis (by class) · other glomerulonephritis · antiphospholipid nephropathy or thrombotic microangiopathy · drug-induced disease (NSAIDs) · infection-related GN · diabetic or hypertensive nephropathy (comorbid) · acute tubular necrosis

Home Meds

• Continue hydroxychloroquine (renoprotective, improves outcomes).

• Start or continue an ACE inhibitor or ARB for proteinuria and BP; immunosuppression per class.

• Hold or adjust if active infection; avoid nephrotoxins (NSAIDs); bone, GI, and glucose protection for steroids; reconcile.

Plan

CONSULT: Nephrology (essential — biopsy, induction and management, RPGN) · Rheumatology (immunosuppression, overall SLE) · ICU if RPGN, severe AKI, or pulmonary-renal disease

• Confirm and classify: a renal biopsy to determine the ISN/RPS class and activity and chronicity (drives whether aggressive induction is needed) — exclude infection and mimics first.

• Proliferative (class III/IV) — prompt induction immunosuppression:

• • High-dose glucocorticoids (IV methylprednisolone pulse for severe disease, then an oral prednisone taper).

• • Plus mycophenolate mofetil or cyclophosphamide (the low-dose "Euro-Lupus" cyclophosphamide regimen — the ELNT trial; or MMF, with comparable efficacy and better tolerability) per nephrology and rheumatology.

• • Consider add-on belimumab or voclosporin or a calcineurin inhibitor (improving renal response per recent trials) per specialist.

• Membranous (class V): RAAS blockade with immunosuppression (MMF or others) if there is significant proteinuria or nephrotic syndrome, per nephrology.

• Mild (class I/II): supportive care and treatment of extrarenal SLE; usually no aggressive nephritis-specific immunosuppression.

• Supportive (all classes): an ACE inhibitor or ARB for proteinuria and BP control (target per guidelines), continue hydroxychloroquine, manage edema and volume, statin and cardiovascular risk reduction, and avoid nephrotoxins.

• Maintenance after induction: mycophenolate or azathioprine for an extended period per specialist; monitor for relapse and drug toxicity; PJP prophylaxis with heavy immunosuppression.

• PT/OT: per functional status.

• Trend: creatinine and eGFR, proteinuria, urine sediment, complement (rising = improving), anti-dsDNA, BP, edema and volume, the response to induction, and infection or drug toxicity.

• Escalation triggers: rapidly progressive glomerulonephritis (a rapidly rising creatinine) → urgent nephrology, aggressive induction, and possible plasma exchange, dialysis, and ICU; pulmonary-renal syndrome → ICU; nephrotic complications (thrombosis, severe edema) → manage; a serious infection on immunosuppression → treat and adjust.

• Discharge checklist: a biopsy-confirmed class with induction underway (proliferative) or a supportive plan (mild); an immunosuppression and maintenance plan; an ACE/ARB; hydroxychloroquine continued; a BP target; PJP and bone, GI, and glucose prophylaxis; nephrology and rheumatology follow-up; adherence and pregnancy counseling (cyclophosphamide); return precautions for decreased urine, worsening edema, rising weight, fever or infection, or BP.

Red Flags

• A rapidly rising creatinine with an active sediment → rapidly progressive glomerulonephritis; urgent biopsy and induction.

• Proliferative (class III/IV) disease left untreated → irreversible renal loss; prompt induction immunosuppression.

• Active sediment and proteinuria in a "well" lupus patient → silent nephritis; pursue it.

• Fever before immunosuppression → exclude infection, which the therapy would worsen.

• Schistocytes with thrombocytopenia and renal failure → thrombotic microangiopathy overlap; a different pathway.

Senior IM Resident Pearls

• It's silent — go looking. A urinalysis with microscopy and protein quantification belong in every lupus evaluation.

• The biopsy class drives everything. Mild mesangial disease needs support; proliferative class III/IV needs prompt induction; membranous class V is nephrotic.

• Proliferative disease is the urgent one. High-dose steroids plus mycophenolate or Euro-Lupus cyclophosphamide, increasingly with belimumab or voclosporin.

• ACE/ARB and hydroxychloroquine for everyone. They cut proteinuria, control pressure, and protect the kidney across all classes.

• Euro-Lupus lowered the cyclophosphamide dose. The ELNT regimen achieves efficacy with less toxicity and preserved fertility.

• Watch complement and dsDNA. A rising complement signals response; a falling one with rising dsDNA signals activity.

• Common mistake: treating the systemic lupus and never quantifying the proteinuria or pursuing the biopsy — the silent nephritis progresses unseen.

Rheumatology — Myopathy

110. Inflammatory Myopathy

/InflammatoryMyopathy · polymyositis · dermatomyositis · immune-mediated necrotizing myopathy · proximal weakness + elevated CK · screen for malignancy and ILD, treat with glucocorticoids + steroid-sparing agents · Super Compact

Sx: symmetric PROXIMAL muscle weakness (difficulty climbing stairs, rising from a chair, lifting arms overhead) developing over weeks-months, ± myalgia; dermatomyositis adds skin findings (Gottron papules over knuckles, heliotrope rash on eyelids, shawl/V sign, mechanic's hands); dysphagia, dyspnea (ILD/respiratory muscle), constitutional symptoms · (two things must be actively screened for in every inflammatory myopathy because they change the whole picture: an underlying malignancy, especially with dermatomyositis, and interstitial lung disease, which is a major driver of morbidity and mortality and is associated with specific myositis antibodies)

Neg: denies missed malignancy screen (esp dermatomyositis — paraneoplastic association) · denies missed interstitial lung disease (anti-Jo1, anti-MDA5 — major morbidity/mortality) · denies statin-associated immune-mediated necrotizing myopathy missed (HMGCR antibody — persists after stopping statin) · denies missed dysphagia/aspiration risk or respiratory muscle weakness · denies attributing weakness to steroids (steroid myopathy) without reassessment · denies missed myocarditis

SHx: weakness onset/progression, skin changes, dysphagia, dyspnea, statin use, malignancy history/age-appropriate screening status, prior autoimmune disease, occupational/functional impact, family history

Etiology: autoimmune muscle inflammation — polymyositis (T-cell-mediated), dermatomyositis (humoral/complement, perimysial, + skin + cancer association), immune-mediated necrotizing myopathy (often anti-SRP or anti-HMGCR — including statin-associated), inclusion body myositis (older, distal/asymmetric, refractory); myositis-specific antibodies define subsets + complication risk

RF: autoimmune predisposition · malignancy (dermatomyositis) · statin exposure (necrotizing) · specific antibody profiles (ILD risk) · age/sex by subtype

Data: elevated creatine kinase (CK — often markedly), aldolase, AST/ALT/LDH (muscle origin) · EMG (myopathic), MRI (muscle edema), muscle biopsy (definitive — inflammation/necrosis pattern) · myositis-specific/associated antibodies (anti-Jo1 and other anti-synthetases → ILD; anti-MDA5 → rapidly progressive ILD/amyopathic DM; anti-HMGCR/anti-SRP → necrotizing; anti-Mi2 → classic DM); malignancy screening (age-appropriate + CT chest/abd/pelvis, esp DM); pulmonary function tests + HRCT chest (ILD); swallow evaluation; TSH (mimic)

DDx: polymyositis · dermatomyositis · immune-mediated necrotizing myopathy (incl statin-associated) · inclusion body myositis · drug-induced/statin myopathy · hypothyroid myopathy · muscular dystrophy · metabolic myopathy · rhabdomyolysis · steroid myopathy · paraneoplastic

Home Meds: stop statin if statin-associated necrotizing myopathy suspected (but HMGCR antibody disease persists/progresses and needs immunosuppression); reconcile; plan immunosuppression + PJP/bone/GI/glucose prophylaxis for prolonged steroids/immunosuppression

Plan

CONSULT: Rheumatology (diagnosis, immunosuppression) · Neurology (EMG, biopsy, diagnosis) · Pulmonology (ILD — esp anti-synthetase/MDA5) · Oncology (malignancy if found) · Speech/swallow (dysphagia) · ICU if respiratory failure/severe dysphagia

– CONFIRM DIAGNOSIS: CK + autoantibodies + EMG + MRI; muscle biopsy for definitive diagnosis/subtype (skin biopsy for DM rash); characterize the subset (antibody profile predicts ILD/cancer risk)
– SCREEN FOR THE TWO KEY ASSOCIATIONS:
  • MALIGNANCY (esp dermatomyositis): age-appropriate screening + CT chest/abdomen/pelvis ± targeted workup (paraneoplastic — cancer can present concurrently)
  • INTERSTITIAL LUNG DISEASE: PFTs + HRCT chest, especially with anti-synthetase (anti-Jo1) or anti-MDA5 (rapidly progressive ILD) — a leading cause of mortality
– TREAT:
  • High-dose glucocorticoids — prednisone ~1 mg/kg/day (IV methylprednisolone pulse for severe/rapidly progressive disease, severe dysphagia, or ILD), then taper
  • Steroid-sparing immunosuppressant early: methotrexate or azathioprine (or mycophenolate); IVIG (effective, esp dermatomyositis, severe dysphagia, refractory); rituximab for refractory per rheumatology
  • ILD (esp MDA5/anti-synthetase): aggressive immunosuppression (often mycophenolate/cyclophosphamide/rituximab ± calcineurin inhibitor) per pulmonology/rheumatology — can be rapidly fatal
– SUPPORTIVE: aspiration precautions/swallow evaluation, respiratory monitoring, PT, skin care (DM), VTE prophylaxis
– STATIN-ASSOCIATED NECROTIZING MYOPATHY: stop the statin AND immunosuppress (anti-HMGCR disease is autoimmune and progresses despite statin cessation — distinguishes from self-limited statin myalgia)
– Inflammatory myopathy presents as someone who can't climb stairs or lift their arms, with a high CK — but the diagnosis isn't complete until you've done two screens that change the entire trajectory. The first is for cancer, because dermatomyositis in particular is paraneoplastic, and the malignancy may be sitting there waiting to be found on the CT you order. The second is for interstitial lung disease, which is the quiet killer of this group — certain antibodies, the anti-synthetases like Jo1 and especially anti-MDA5, carry a high risk of ILD that can progress rapidly to respiratory failure, so the PFTs and HRCT aren't optional. The treatment is high-dose steroids with an early steroid-sparing agent, escalating to IVIG or rituximab and, for the dangerous ILD, to aggressive combination immunosuppression. And there's one trap worth knowing cold: the statin-associated immune-mediated necrotizing myopathy with the anti-HMGCR antibody does NOT resolve when you stop the statin — it's a true autoimmune disease that keeps progressing and needs immunosuppression, unlike ordinary statin myalgia.
– PT/OT: essential — strengthening (as inflammation controlled), functional rehab, swallow therapy, fall prevention
– Trend: muscle strength (clinical), CK trajectory (response/relapse), respiratory function (ILD/muscle), swallow/aspiration, malignancy workup results, steroid complications, distinguishing steroid myopathy from active disease
– Escalation triggers: rapidly progressive ILD (esp anti-MDA5) / respiratory failure → ICU + aggressive combination immunosuppression + pulmonology; severe dysphagia/aspiration → swallow eval + airway protection ± IVIG pulse; myocarditis → cardiology + ICU; malignancy found → oncology; refractory disease → IVIG/rituximab + rheumatology
– Discharge checklist: diagnosis + subtype confirmed (antibodies/biopsy); malignancy screen + ILD evaluation done; immunosuppression regimen (steroids + steroid-sparing ± IVIG) + taper; statin stopped if HMGCR; PJP/bone/GI/glucose prophylaxis; rheumatology + neurology (+ pulmonology/oncology) follow-up; PT/swallow arranged; return precautions (worsening weakness, dyspnea, dysphagia/choking, rash spread, chest symptoms)

110. Inflammatory Myopathy

/InflammatoryMyopathy · complete reference · proximal weakness + high CK · biopsy/antibody subtyping, mandatory malignancy + ILD screening, glucocorticoids plus steroid-sparing therapy · Full Card

Symptoms / Associated Sx

• Symmetric proximal muscle weakness (difficulty climbing stairs, rising from a chair, lifting the arms overhead) developing over weeks to months, with or without myalgia

• Dermatomyositis adds skin findings (Gottron papules over the knuckles, a heliotrope rash on the eyelids, a shawl or V sign, mechanic's hands); dysphagia, dyspnea (ILD or respiratory muscle), and constitutional symptoms

• Two things must be actively screened for in every inflammatory myopathy because they change the whole picture: an underlying malignancy, especially with dermatomyositis, and interstitial lung disease, which is a major driver of morbidity and mortality and is associated with specific myositis antibodies

Neg

• Pt denies a missed malignancy screen (especially dermatomyositis — a paraneoplastic association) and missed interstitial lung disease (anti-Jo1, anti-MDA5 — major morbidity and mortality).

• Pt denies a missed statin-associated immune-mediated necrotizing myopathy (the HMGCR antibody — which persists after stopping the statin) and missed dysphagia, aspiration risk, or respiratory muscle weakness.

• Pt denies attributing weakness to steroids (steroid myopathy) without reassessment and a missed myocarditis.

Social History (SHx)

• Weakness onset and progression, skin changes, dysphagia, and dyspnea.

• Statin use and malignancy history or age-appropriate screening status.

• Prior autoimmune disease, occupational and functional impact, and family history.

Main Etiology

• Autoimmune muscle inflammation — polymyositis (T-cell-mediated), dermatomyositis (humoral and complement-mediated, perimysial, with skin involvement and a cancer association)

• Immune-mediated necrotizing myopathy (often anti-SRP or anti-HMGCR — including statin-associated disease)

• Inclusion body myositis (older patients, distal and asymmetric, refractory); myositis-specific antibodies define the subsets and complication risk

RF

• Modifiable: statin exposure (necrotizing myopathy).

• Non-modifiable: autoimmune predisposition, malignancy (dermatomyositis), specific antibody profiles (ILD risk), and age and sex by subtype.

Data

• An elevated creatine kinase (CK — often markedly), aldolase, and AST, ALT, and LDH (of muscle origin)

• EMG (myopathic), MRI (muscle edema), and a muscle biopsy (definitive — the inflammation or necrosis pattern)

• Myositis-specific and associated antibodies (anti-Jo1 and other anti-synthetases → ILD; anti-MDA5 → rapidly progressive ILD or amyopathic DM; anti-HMGCR and anti-SRP → necrotizing disease; anti-Mi2 → classic DM)

• Malignancy screening (age-appropriate plus CT chest, abdomen, and pelvis, especially in DM); pulmonary function tests and HRCT chest (ILD); a swallow evaluation; TSH (a mimic).

DDx

Polymyositis · dermatomyositis · immune-mediated necrotizing myopathy (including statin-associated) · inclusion body myositis · drug-induced or statin myopathy · hypothyroid myopathy · muscular dystrophy · metabolic myopathy · rhabdomyolysis · steroid myopathy · paraneoplastic syndrome

Home Meds

• Stop the statin if statin-associated necrotizing myopathy is suspected (but HMGCR antibody disease persists and progresses and needs immunosuppression).

• Plan immunosuppression with PJP, bone, GI, and glucose prophylaxis for prolonged steroids and immunosuppression.

• Reconcile medications.

Plan

CONSULT: Rheumatology (diagnosis, immunosuppression) · Neurology (EMG, biopsy, diagnosis) · Pulmonology (ILD — especially anti-synthetase or MDA5) · Oncology (malignancy if found) · Speech and swallow (dysphagia) · ICU if respiratory failure or severe dysphagia

• Confirm the diagnosis: CK, autoantibodies, EMG, and MRI; a muscle biopsy for definitive diagnosis and subtype (a skin biopsy for the DM rash); characterize the subset (the antibody profile predicts ILD and cancer risk).

• Screen for the two key associations:

• • Malignancy (especially dermatomyositis): age-appropriate screening plus CT chest, abdomen, and pelvis with possible targeted workup (paraneoplastic — the cancer can present concurrently).

• • Interstitial lung disease: PFTs and HRCT chest, especially with anti-synthetase (anti-Jo1) or anti-MDA5 (rapidly progressive ILD) — a leading cause of mortality.

• Treat:

• • High-dose glucocorticoids — prednisone ~1 mg/kg/day (IV methylprednisolone pulse for severe or rapidly progressive disease, severe dysphagia, or ILD), then taper.

• • A steroid-sparing immunosuppressant early: methotrexate or azathioprine (or mycophenolate); IVIG (effective, especially in dermatomyositis, severe dysphagia, or refractory disease); rituximab for refractory disease per rheumatology.

• • ILD (especially MDA5 or anti-synthetase): aggressive immunosuppression (often mycophenolate, cyclophosphamide, or rituximab with a calcineurin inhibitor) per pulmonology and rheumatology — can be rapidly fatal.

• Supportive care: aspiration precautions and a swallow evaluation, respiratory monitoring, PT, skin care (DM), and VTE prophylaxis.

• Statin-associated necrotizing myopathy: stop the statin and immunosuppress (anti-HMGCR disease is autoimmune and progresses despite statin cessation — distinguishing it from self-limited statin myalgia).

• PT/OT: essential — strengthening (as inflammation is controlled), functional rehabilitation, swallow therapy, and fall prevention.

• Trend: muscle strength (clinical), the CK trajectory (response or relapse), respiratory function (ILD or muscle), swallow and aspiration, malignancy workup results, steroid complications, and distinguishing steroid myopathy from active disease.

• Escalation triggers: rapidly progressive ILD (especially anti-MDA5) or respiratory failure → ICU, aggressive combination immunosuppression, and pulmonology; severe dysphagia or aspiration → swallow evaluation and airway protection with a possible IVIG pulse; myocarditis → cardiology and ICU; malignancy found → oncology; refractory disease → IVIG or rituximab and rheumatology.

• Discharge checklist: the diagnosis and subtype confirmed (antibodies, biopsy); a malignancy screen and ILD evaluation done; an immunosuppression regimen (steroids with a steroid-sparing agent and possible IVIG) and a taper; the statin stopped if HMGCR; PJP, bone, GI, and glucose prophylaxis; rheumatology and neurology (and pulmonology and oncology) follow-up; PT and swallow therapy arranged; return precautions for worsening weakness, dyspnea, dysphagia or choking, rash spread, or chest symptoms.

Red Flags

• Dermatomyositis → a paraneoplastic malignancy may be present; screen with age-appropriate tests and CT chest, abdomen, and pelvis.

• Anti-MDA5 or anti-synthetase antibodies → rapidly progressive interstitial lung disease that can be fatal; image and treat aggressively.

• Statin myopathy that progresses after stopping the statin → anti-HMGCR immune-mediated necrotizing myopathy; immunosuppress.

• Severe dysphagia → aspiration risk; swallow evaluation and airway protection.

• Worsening weakness on steroids → distinguish active disease from steroid myopathy before escalating.

Senior IM Resident Pearls

• Two screens complete the diagnosis. Cancer (especially in dermatomyositis) and interstitial lung disease change the entire trajectory.

• ILD is the quiet killer. Anti-synthetase and especially anti-MDA5 antibodies carry a high risk of rapidly progressive lung disease — get the PFTs and HRCT.

• The statin myopathy that won't quit is autoimmune. Anti-HMGCR necrotizing myopathy progresses after stopping the statin and needs immunosuppression.

• Treat early with a steroid-sparing agent. High-dose steroids alone leave the patient on too much for too long — add methotrexate, azathioprine, or IVIG early.

• Antibodies predict the complications. The myositis-specific antibody profile forecasts ILD and cancer risk and guides intensity.

• Don't blame steroids for new weakness reflexively. Steroid myopathy and active disease both weaken — the CK and the pattern help distinguish.

• Common mistake: diagnosing dermatomyositis and treating the muscle without ever screening for the malignancy that may be driving it.