Medicine Exam 5: Miscellaneous Rheumatology

Lecture 2

Angiography

· Detect aneurysms in PAN

Arthrocentesis

· Diagnostic for gout (urate crystals) and pseudogout (CPP crystals)

Biopsy (skin, nerve, organ)

· Diagnostic for PAN

Chronic Fatigue – Clinically Relevant Fatigue

Clinically significant fatigue - Difficulty starting activities - Difficulty completing activities - Difficulty with concentration and memory

Chronic Fatigue – Diagnosis

· - clinically significant fatigue lasting more than 6 months · Diagnosis of exclusion, all other tests ill be negative · Extreme malaise and unwell with more attempts to do ADL · May only feel well when laying down or in reclining position = may present with or without orthostatic hypotension

Chronic Fatigue – Diagnostic Studies

• All will be normal in chronic fatigue syndrome - Rule out other causes of fatigue/weakness: • Thyroid disease • Parathyroid disease • Heart failure • Infections (EBV, Lyme, HIV, COVID) • COPD/Asthma or interstitial lung disease • Renal disease • Sleep apnea • Anemia • Autoimmune disorders • Cancer

Chronic Fatigue – Patient Evaluation: History

• Daily activities - Occupation - Diet - Alcohol use disorder - Medications - Psychiatric comorbidities

Chronic Fatigue – Patient population

Autoimmune conditions in general commonly population of female in child bearing age, may be associated with hormone levels worsen post partum

Chronic Fatigue – SEID: Diagnostic Criteria

• ALL of the below: • Substantial reduction or impairment in ability to function > 6 months due to profound fatigue of new or defined onset • Fatigue is not alleviated by rest • Post-exertional malaise • Unrefreshing sleep - PLUS at least one of the following: • Cognitive impairment, OR • Orthostatic intolerance

Chronic Fatigue – Treatment

Focus on lifestyle modifications and non pharmacologic

Chronic Fatigue –Treatment

• Identify and treat any underlying causes - Treat associated orthostatic intolerance: • Fluid (2L daily) and salt intake (liberal salt with water level) • Fludrocortisone • Midodrine - Aerobic exercise - Insufficient and/or inconsistent evidence for most pharmaceuticals, including: • Methylphenidate • Pitolisant • Modafinil • Bupropion • Testosterone (men >65 only) • Vitamin D • Naltrexone - Non-pharmacologic: • Cognitive behavioral therapy • Massage therapy • Acupuncture

Chronic Fatigue Syndrome

• AKA systemic exertion intolerance disease (SEID) - No objective findings on physical exam or laboratory/diagnostic workup - Pathophysiology unknown

Chronic Fatigue Syndrome (SEID)

• Pathophysiology unknown; no objective findings - Symptoms: difficulty initiating/completing activities, poor concentration/memory - Evaluation: assess daily activities, occupation, diet, alcohol, meds, psych comorbidities - Diagnosis: rule out thyroid, parathyroid, HF, infections, lung disease, renal disease, anemia, autoimmune, cancer - Criteria: >6 months fatigue, not relieved by rest, post-exertional malaise, unrefreshing sleep + cognitive impairment or orthostatic intolerance - Treatment: treat underlying causes; fluids/salt, fludrocortisone, midodrine; aerobic exercise; CBT, massage, acupuncture; limited evidence for meds

Chronic Fatigue Syndrome Pathway OVerall

1. Symptoms of prolonged or chronic fatigue 2. History and physical examination · If abnormal (findings of infection, neoplasm, or thyroid disease), pursue appropriate diagnostic tests 3. Mental status examination · If abnormal, evaluate with psychiatric or neurologic examination 4. Laboratory testing (CBC, ESR, serum electrolytes, glucose, BUN, creatinine, alkaline phosphatase, ALT, Ca2+, PO43-, total protein, globulin, albumin, TSH, and UA) · If abnormal, pursue appropriate further diagnostic evaluation 5. If fatigue persists or relapses for ≥ 6 months, diagnose either chronic fatigue syndrome or idiopathic chronic fatigue, accordingly 6. Chronic Fatigue Syndrome · Criteria for severity of fatigue are met AND four or more of the following symptoms are concurrently present for > 6 months: · · Pharyngitis · . Tender cervical or axillary lymph nodes · · Myalgias · · Polyarthralgia · . New headaches · · Sleep that patient reports as unrefreshing · . Postexertion malaise · . Memory or concentration impairment 7. Idiopathic Chronic Fatigue · Criteria for fatigue severity or symptoms of chronic fatigue syndrome are NOT met

Colchicine

· Used in gout and pseudogout (acute and prophylaxis)

Cyclophosphamide

· Used in severe PAN

ESR

· ESR stands for erythrocyte sedimentation rate. It’s a blood test that measures how quickly red blood cells settle at the bottom of a test tube over one hour. · A faster-than-normal rate may indicate inflammation somewhere in the body. · It’s a nonspecific marker, meaning it doesn’t pinpoint the cause but can support diagnoses like polymyalgia rheumatica, temporal arteritis, or autoimmune conditions. · ESR is often used alongside other tests to monitor disease activity or response to treatment.

ESR/CRP

· Elevated in GCA, PMR, PAN

Fatigue

• Vague, poorly defined symptom - Associated symptoms: weakness, lethargy - Possible lifestyle causes: • Overexertion • Deconditioning • Poor sleep habits • Obesity • Poor nutrition • Emotional disturbances or stress

Fibromyalgia

• Cause unknown; no objective findings or diagnostic tests - Theories: aberrant pain perception, sleep disorders, depression, viral infections - Associated: hypothyroidism, RA, OSA, IBS - Symptoms: chronic ache, stiffness, fatigue, sleep disorder, headaches, GI symptoms (IBS), no fever/weight loss - Diagnosis: clinical; widespread pain >3 months; 11/18 trigger points - Workup: rule out RA, SLE, hypothyroidism, PMR, Lyme, electrolytes - Treatment: education, exercise, CBT, meditation; meds include duloxetine, amitriptyline, cyclobenzaprine, pregabalin, gabapentin, tramadol/APAP; avoid opioids

Fibromyalgia – Diagnostic Testing

• All normal - Clinical diagnosis: widespread pain > 3 months with no identified cause, diffuse vague sensations pain NONE: - RA, SLE - Hypothyroidism - Polymyositis (weakness >> pain) - PMR - Electrolyte abnormalities - Lyme disease Past - Increased pain in 11/18 trigger points Now do not just look at trigger points

Fibromyalgia – Etiology/ Pathophysiology

• Cause unknown - Absence of objective findings or diagnostic test results - Theories: • Aberrant perception of pain • Sleep disorders • Depression • Viral infections - Associated conditions: • Hypothyroidism • RA • OSA • IBS Pain everywhere, diffuse aches and pains everywhere Normal diagnostic tests

Fibromyalgia – Signs and Symptoms

• Chronic ache - Stiffness, “numbness” - Complaints involve entire body - Complaint Foci: neck, shoulders, low back, hips - Fatigue/sleep disorder - Chronic headaches - GI findings (IBS) - Absence of fever, weight loss

Fibromyalgia – Treatment (Conservative)

• Patient education - Exercise program - Cognitive behavioral therapy = ex. Meditation

Fibromyalgia – Treatment (Medication)

• Medications: • Duloxetine (Cymbalta) • Amitriptyline • Cyclobenzaprine • Pregabalin • Gabapentin May help • Tramadol, APAP - Do NOT use opioids: • No proven benefit • Addictive properties

Fibromyalgia diagnosis sigma

People say they don’t believe in living in chronic pain; people say that there is nothing wrong with you, it is all in your head Validation that it is a real diagnosis Give theories and show understanding

Fibromyalgia pharmacology

Anti-inflammatory medications will not help, opioids will bring SUB Avoid chronic NSAID use Treatment more like neurologic pain = treat as neuropathic pain

Giant Cell Arteritis – Diagnostic Testing

ESR elevated = very sensitive for temporal arteritis - >50, often >100 CRP - Can be normal with bx-proven disease - Mild anemia (chronic inflammation) - Thrombocytosis - Elevated Alk Phos - POCUS = temporal artery - Temporal Artery Biopsy – confirmatory

Giant Cell Arteritis – Emergency

Need to preserve vision, can be an emergency if do not treat with steroids immediately If vision loss ake place, typically not regersisble

Giant Cell Arteritis – Etiology & Pathophysiology

• Systemic pan-arteritis -Medium and large vessels - Temporal artery - Extracranial branches of carotid artery - 85% of patients have evidence of large vessel inflammation on PET-CT, asymptomatic

Giant Cell Arteritis – Risk Factors

• Age >50, average age of onset 79 - Association with polymyalgia rheumatica

Giant Cell Arteritis – Signs and Symptoms (Aortic/Systemic)

• If aorta affected: • Asymmetric pulses in UE • Aortic regurgitation • Bruits near clavicle = Subclavian artery stenosis - Systemic/non-specific symptoms: • Cough • Painful shoulder paralysis • Fever with rigors/sweats (as high as 104) • Unexplained head or neck pain = Pain of tongue, nose, ears

Giant Cell Arteritis – Signs and Symptoms (Cranial)

• Headache (temporal area) - Scalp tenderness - Jaw claudication (highest positive predictive value) - Throat pain Vision change: - Amaurosis fugax - Diplopia Physical Exam – usually normal - May have tenderness over temporal artery, or may be nodular, enlarged, or pulseless

Giant Cell Arteritis – Treatment

Urgent initiation of high-dose steroids - Prevent blindness, it is irreversible - Don’t need to wait for biopsy - Prednisone 60mg daily prior to onset of visual symptoms - IV Methylprednisolone, 1g daily if pt c/o vision loss - Begin tapering steroids after 1 month = Consider using ESR as a guide Can take a year to taper off Low dose aspirin = help with residual inflamed vessels

Giant Cell Arteritis (GCA)

• Systemic pan-arteritis of medium/large vessels; affects temporal and extracranial carotid branches - Risk: age >50 (avg 79), PMR association - Symptoms: headache, scalp tenderness, vision changes, jaw claudication, throat pain; aortic involvement → asymmetric pulses, regurgitation, bruits - Diagnosis: ESR >50 (often >100), CRP, anemia, thrombocytosis, elevated Alk Phos, POCUS, temporal artery biopsy - Treatment: high-dose steroids (prednisone 60mg or IV methylprednisolone if vision loss); taper after 1 month; low-dose aspirin - Complication: irreversible blindness

Gout

• Most common inflammatory arthritis in US - Risk: Pacific Islander, hereditary, diuretics, ASA, cyclosporine, niacin, alcohol, CKD, hypothyroidism, psoriasis, sarcoidosis, lead poisoning - Pathophysiology: hyperuricemia (under-excretion > overproduction); urate crystal deposition → inflammation - Symptoms: acute arthritis (1st MTP “podagra”), intense night pain - Exam: red, warm, swollen joint; desquamation, pruritus, fever; tophi (ears, feet, bursae, hands) - Diagnosis: serum uric acid (↑ in 95%, normal in 25% acute); leukocytosis; arthrocentesis (needle-shaped, negatively birefringent crystals); X-ray: “rat bite” erosions in chronic gout - Treatment: NSAIDs, colchicine (within 36h), corticosteroids; avoid rapid uric acid drop - Prophylaxis: diet (low purine, ↑ fluids), avoid alcohol/thiazides; meds: colchicine, allopurinol, probenecid, uricase

Gout – Diagnostic Testing

• Serum uric acid level: • Hyperuricemia in 95% of patients • Uric acid normal during 25% acute attacks - Leukocytosis - Arthrocentesis = diagnostic: • Monosodium urate crystals • Needle-shaped • Negatively birefringent

Gout – Diagnostic Testing (continued)

• Radiographs: • Acute attacks usually normal • Chronic – “Rat Bite” appearance = Punched-out erosions with a rim of cortical bone

Gout – Etiology & Pathophysiology

• Hyperuricemia: • Under-excretion of uric acid (more common) = Cleared by kidneys • Overproduction of uric acid (due to ↑ purine metabolism) - Abnormal deposits of urate in tissues - Monosodium urate crystals = - Pro-inflammatory → interleukin production

Gout – Exam Findings

• Red, warm, swollen joint - Local desquamation and pruritus - Fever - Tophi: • Ears • Feet • Olecranon & pre-patellar bursae • Hands

Gout – General

• MOST COMMON INFLAMMATORY ARTHRITIS IN US

Gout – Prophylaxis (Lifestyle)

• Diet: • Avoid beer/alcohol • Low purine diet • Increase liquids • Goal urine output >2L/day - Medication adjustments: • Avoid thiazide diuretics, niacin

Gout – Prophylaxis (Medication)

• Colchicine: • Use in conjunction with urate-lowering therapy • Monotherapy for mild hyperuricemia, rare attacks - Urate-Lowering Therapy: • Indications: >2 episodes/year, tophi, CKD • Classes: • Xanthine oxidase inhibitor (allopurinol) • Uricosuric agent (probenecid) • Uricase

Gout – Risk Factors

• Pacific Islander ethnicity - Hereditary - Medications: • Diuretics • ASA • Cyclosporine • Niacin - Alcohol ingestion - Diet - Myeloproliferative disorders = ex. Multiple myeloma - Hemoglobinopathies - Chronic kidney disease - Hypothyroidism - Psoriasis - Sarcoidosis - Lead poisoning

Gout – Signs and Symptoms

• Acute onset arthritis - Most common joint = 1st MTP joint (“podagra”) - Worse at night - Intense pain

Gout – Treatment (Acute Attack)

• Goal = reduce inflammation - NSAIDs: • Naproxen, indomethacin • Continue 5–10 days, until symptoms resolved - Colchicine: • Start within 36 hours of symptom onset - Corticosteroids: • Systemic or intra-articular • Rule out septic arthritis - Avoid rapid lowering of uric acid

Gout Spiral

· Attack Starts · Crystals Form · White blood cells attack · Crystals 'pop' the cell · Cell releases proteins · Proteins 'call in' more white blood cells and cause inflammation/pain · Proteins lower pH making it possible for more crystals to form

Gout vs. Pseudogout

Gout · Uric acid crystals · Tophi · Negatively birefringent needle-shaped crystals · Most common site is t the first MTP Joint = Podagra Pseudogout · Usually affects larger joints such as the knee · Chondrocalcinosis on radiographs · Calcium pyrophosphate dihydrate (CPPD) crystals · Positively birefringent rhomboid-shaped crystals

Hepatitis B

Polyarteritis Nodosa appears in 10% of Hep B cases

Joint Pain

• Fibromyalgia (widespread pain, no inflammation) - PMR (pain/stiffness in shoulders/pelvis) - PAN (arthralgia, extremity pain) - Gout (acute, intense pain in 1st MTP) - Pseudogout (acute pain in large joints) - RA (mentioned in fibromyalgia differential)

Joint Swelling

• Gout (red, warm, swollen joint) - Pseudogout (acute arthritis with swelling) - PAN (skin nodules, ulcers near joints) - RA (mentioned as a cause of dislocation and in fibromyalgia differential)

Lethargy

More extreme than fatigue

NSAIDs

· Used in gout and pseudogout (acute)

POCUS

· Used in GCA evaluation

Polyarteritis Nodosa – Diagnostic Testing

• CBC: • Mild anemia • Leukocytosis - Inflammatory markers: • Usually elevated - ANCA negative - Hepatitis B serologies - No reliable lab studies, no specific antibody

Polyarteritis Nodosa – Diagnostic Testing (continued)

• Tissue biopsy – diagnostic: • Skin biopsy (at ulcer or nodule site) • Nerve biopsy • Biopsy of affected organ - Angiography: • Aneurysmal dilation in renal, mesenteric, or hepatic artery

Polyarteritis Nodosa – Etiology & Pathophysiology

• Definition: necrotizing arteritis of medium-sized vessels - Involves skin, peripheral nerves, mesenteric vessels, heart, and brain preferentially - Can involve any organ - Kidney – frequently involved - SPARES the lung

Polyarteritis Nodosa – Medical History

• First reported form of vasculitis = 1866 - Had been an umbrella term for all vasculitis until recent years

Polyarteritis Nodosa – Prognosis

• 5-year survival: • No treatment: 10% • Appropriate treatment: 60–90% - Poor prognosis: • Chronic kidney disease • Cardiac involvement • CNS involvement • Mesenteric ischemia - Relapses uncommon after remission

Polyarteritis Nodosa – Risk Factors

• Rare disease – 30 in 1 million - Hepatitis B • Causes 10% of cases within 6 months of HBV infection - Familial • Adenosine deaminase 2 gene mutation

Polyarteritis Nodosa – Signs and symptoms

Can impact every part of the body except the lungs

Polyarteritis Nodosa – Signs and Symptoms (Cardiac)

• MI - Myocarditis

Polyarteritis Nodosa – Signs and Symptoms (General)

• Symptoms develop over weeks–months - Fever, malaise, weight loss Pain in extremities - Arthralgias - Myalgias (calves) - Neuropathy Mononeuritis multiplex - Foot-drop

Polyarteritis Nodosa – Signs and Symptoms (GI)

• Abdominal pain worse with eating - N/V Organ infarction or micro-aneurysms - Cholecystitis - Appendicitis - Bowel perforation - Hypotension

Polyarteritis Nodosa – Signs and Symptoms (Renal)

• Renal artery involvement - Hypertension

Polyarteritis Nodosa – Signs and Symptoms (Skin)

• Livedo reticularis - Subcutaneous nodules - Skin ulcers – most common skin finding • Near malleoli - Digital gangrene

Polyarteritis Nodosa – Treatment

• High dose steroids: • Fever, ulcers, constitutional symptoms: oral prednisone • Critically ill: IV methylprednisolone - Cyclophosphamide: • Lowers morbidity and mortality in patients with severe disease - Hepatitis B + Polyarteritis nodosa: • Prednisone + antivirals + plasmapheresis

Polyarteritis Nodosa (PAN)

• Necrotizing arteritis of medium vessels; affects skin, nerves, mesenteric vessels, heart, brain; spares lungs - Risk: rare (30/million); Hep B (10% within 6 months); ADA2 gene mutation - Symptoms: fever, malaise, weight loss, extremity pain, arthralgia, calf myalgia, neuropathy (foot drop), livedo reticularis, nodules, ulcers, gangrene, HTN, GI pain, infarction, cardiac symptoms - Diagnosis: CBC (anemia, leukocytosis), elevated inflammatory markers, ANCA negative, Hep B serologies; biopsy (skin, nerve, organ); angiography (aneurysms) - Treatment: high-dose steroids; cyclophosphamide for severe disease; Hep B cases → prednisone + antivirals + plasmapheresis - Prognosis: 5-year survival 10% untreated, 60–90% treated; poor with CKD, cardiac/CNS/mesenteric involvement

Polymyalgia Rheumatica – Diagnosis

Inflammation blood vessels Vasculitis that impacts arteries = arteritis Clinical based on history, no objective weakness Start on steroids = feel better within a week, if it does not then probably wrong diagnosis

Polymyalgia Rheumatica – Diagnostic Testing

• Clinical Diagnosis - May see: • Anemia • Elevated ESR - …or labs may be normal

Polymyalgia Rheumatica – Etiology & Pathophysiology

• Systemic pan-arteritis - Medium and large vessels predominantly - Cytokine-mediated - On same spectrum of disease as GCA (giant sign or temporal arteritis)

Polymyalgia Rheumatica – GCA Association

Typically have Polymyalgia Rheumatica take place before emerge commonly

Polymyalgia Rheumatica – Pain

Not weakness on exam, but exertion pain will cause lower strength testing Limited mobility because of pain

Polymyalgia Rheumatica – Signs and Symptoms

• Pain and stiffness: • Pelvic girdle • Shoulder - Fever, malaise, weight loss - 1/3 of cases associated with GCA, 2/3 occur alone - Typical patient complaints: • Can’t brush hair • Put on a coat • Get out of a chair - No weakness on exam

Polymyalgia Rheumatica – Treatment

• Low dose steroids = Significant improvement in 3 days - Taper steroid after 1 month = Continue at low dose for 1 year May be on prednisone for rest of life, very low dose 1-2mg so little harmful effects Chronic steroid use indicate GI prophylaxis need for prevention

Polymyalgia Rheumatica (PMR)

• Systemic pan-arteritis; cytokine-mediated; same spectrum as GCA - Symptoms: pain/stiffness in pelvic girdle and shoulders; fever, malaise, weight loss; no weakness - Diagnosis: clinical; may show anemia, elevated ESR - Treatment: low-dose steroids; rapid improvement in 3 days; taper after 1 month; continue low dose for 1 year

Pseudogout – Definitions

• Chondrocalcinosis = calcium pyrophosphate deposition (CPPD) in fibrocartilage and hyaline cartilage • Radiographic finding • Usually asymptomatic - Pseudogout = acute crystal-induced arthritis as a result of calcium pyrophosphate crystals

Pseudogout – Diagnostic Testing

• Plain films: • Chondrocalcinosis - Arthrocentesis (diagnostic): • Calcium pyrophosphate crystals • Rhomboid-shaped • Positively birefringent

Pseudogout – Etiology & Pathophysiology

• Cause unknown, theories: • Excessive body calcium/metabolic disturbance • Overproduction of pyrophosphate by cartilage chondrocytes - Pathophysiology: • Inflammation via interleukin production due to crystal deposition

Pseudogout – Risk Factors

• Hyperparathyroidism - Hemochromatosis - Hypomagnesemia - Familial CPPD (uncommon) - Age >60 - Previous joint injury - Hypothyroidism

Pseudogout – Signs and Symptoms

• Acute arthritis involving large joints: • Knees • Wrists • Shoulder • Neck - Onset to peak of symptoms within 24 hours

Pseudogout – Treatment

• Acute attacks: • NSAIDs • Intra-articular triamcinolone injection - Prophylaxis: • Colchicine

Pseudogout (CPPD)

• Chondrocalcinosis = CPPD in cartilage (radiographic finding, often asymptomatic) - Pseudogout = acute arthritis from CPP crystals - Risk: hyperparathyroidism, hemochromatosis, hypomagnesemia, hypothyroidism, age >60, prior joint injury - Pathophysiology: excess calcium/metabolic disturbance; pyrophosphate overproduction; crystals → inflammation via interleukins - Symptoms: acute arthritis in large joints (knees, wrists, shoulders, neck); peak within 24h - Diagnosis: plain films (chondrocalcinosis); arthrocentesis (rhomboid-shaped, positively birefringent crystals) - Treatment: NSAIDs, intra-articular triamcinolone; prophylaxis: colchicine

Steroid therapy

· Used in GCA, PMR, PAN, gout (acute), pseudogout

Temporal Arteritis

Normal = vessel hollow, blood flow Pathology = artery becomes severely narrowed

Temporal Artery Biopsy

· Confirmatory for GCA

Term

Definition

Urate-lowering therapy

· Used in gout prophylaxis (allopurinol, probenecid, uricase)