138. Causes that contribute to the development of edema syndrome. 139. Classification of acute circulatory failure. 140. The role of disturbances in osmotic and hydrostatic pressure in the formation of edema. 141. Diagnostic criteria for edema syndrome in heart diseases. 142. Diagnostic criteria for edema syndrome in kidney diseases. 143. Diagnostic criteria for nephrotic syndrome. 144. Mechanisms of edema formation in chronic heart failure. 145. The mechanism of edema formation in nephritic syndrome 146. Mechanisms of edema formation in liver cirrhosis and portal hypertension. 147. Laboratory markers for diagnosing the causes of edema. 148. Principles of treatment of acute and chronic circulatory failure. 149. Classification of joint diseases. 150. Diagnostic criteria for rheumatic polyarthritis. 151. Diagnostic criteria for rheumatoid arthritis. 152. Diagnostic criteria for Felty's syndrome 153. Diagnostic criteria for Still's syndrome 154. Diagnostic criteria for Reiter's syndrome. 155. Diagnostic criteria for systemic lupus erythematosus. 156. Diagnostic criteria for systemic sclerosis. 157. Diagnostic criteria for dermatomyositis 158. Diagnostic criteria for deforming osteoarthritis. 159. Diagnostic criteria for gout. 160. The role of glucocorticosteroids in the treatment of rheumatoid arthritis. 161. Use of cytostatics in the treatment of rheumatoid arthritis.

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Here is a comprehensive set of answers to all 23 questions, drawing from authoritative textbook sources.

EDEMA SYNDROME & CIRCULATORY FAILURE (Questions 138–148)

138. Causes Contributing to the Development of Edema Syndrome

Edema arises from expansion of the interstitial fluid compartment due to one or more of the following mechanisms:

Increased capillary hydrostatic pressure — congestive heart failure (CHF), venous obstruction, portal hypertension
Decreased plasma oncotic (colloid osmotic) pressure — hypoalbuminemia from nephrotic syndrome, cirrhosis, malnutrition, protein-losing enteropathy
Increased capillary permeability — inflammation, allergic reactions, burns, sepsis, ARDS
Lymphatic obstruction — lymphedema (post-surgical, filariasis, malignancy)
Sodium and water retention by the kidney — primary renal disease, activation of RAAS, secondary hyperaldosteronism
Reduced effective arterial blood volume (arterial underfilling) — triggers renal sodium and water retention in CHF, cirrhosis, and nephrotic syndrome

The three major systemic causes are heart failure, cirrhosis with ascites, and nephrotic syndrome. Weight gain of several kilograms typically precedes clinically apparent edema.

— Comprehensive Clinical Nephrology, 7th Edition

139. Classification of Acute Circulatory Failure

Acute circulatory failure (shock) is classified by etiology:

Type	Mechanism	Examples
Hypovolemic	Reduced preload, low circulating volume	Hemorrhage, burns, severe dehydration, vomiting/diarrhea
Cardiogenic	Pump failure; reduced cardiac output	Acute MI, severe arrhythmia, acute valvular failure, myocarditis
Distributive	Abnormal vasodilation, maldistribution of flow	Septic shock, anaphylactic shock, neurogenic shock, adrenal crisis
Obstructive	Mechanical obstruction to flow	Massive pulmonary embolism, cardiac tamponade, tension pneumothorax, aortic stenosis

Functional classification (by hemodynamics):

Low-output failure: cardiogenic, hypovolemic, obstructive — reduced CO, elevated SVR
High-output (distributive) failure: elevated CO early, low SVR, peripheral vasodilation

Chronic heart failure is also classified by:

NYHA Functional Classes I–IV (by symptom severity with exertion)
ACC/AHA Stages A–D (by structural disease and symptoms)
Left-sided vs. right-sided vs. biventricular HF
Systolic (HFrEF) vs. diastolic (HFpEF)

140. Role of Disturbances in Osmotic and Hydrostatic Pressure in Edema Formation

Fluid exchange between plasma and interstitium is governed by the Starling equation:

Net filtration = Kf [(Pc − Pi) − σ(πc − πi)]

Where:

Pc = capillary hydrostatic pressure (drives fluid OUT of capillaries)
Pi = interstitial hydrostatic pressure (resists outflow)
πc = plasma oncotic pressure (draws fluid INTO capillaries)
πi = interstitial oncotic pressure (draws fluid OUT of capillaries)

Increased capillary hydrostatic pressure (Pc↑):

Occurs in CHF (venous congestion), venous obstruction, kidney disease with volume overload
Overwhelms oncotic retention → fluid transudation into interstitium

Decreased plasma oncotic pressure (πc↓):

In nephrotic syndrome, liver failure, malnutrition → hypoalbuminemia
Albumin is the chief determinant of plasma oncotic pressure (normally ~28 mmHg)
Low oncotic pressure shifts net Starling forces toward filtration → edema
Compensatory lymphatic drainage is eventually overwhelmed

Both mechanisms often coexist: In cirrhosis — elevated portal hydrostatic pressure + hypoalbuminemia; in nephrotic syndrome — low oncotic pressure + secondary sodium retention.

— Comprehensive Clinical Nephrology, 7th Edition; Brenner and Rector's The Kidney

141. Diagnostic Criteria for Edema Syndrome in Heart Diseases

Clinical features (Framingham criteria for HF):

Major criteria:

Paroxysmal nocturnal dyspnea (PND) or orthopnea
Neck vein distension (elevated JVP)
Rales (pulmonary crackles)
Cardiomegaly on X-ray
Acute pulmonary edema
S3 gallop
Hepatojugular reflux
Weight loss >4.5 kg in 5 days in response to treatment

Minor criteria:

Bilateral ankle edema
Nocturnal cough
Dyspnea on ordinary exertion
Hepatomegaly
Pleural effusion
Vital capacity reduced by 1/3 from maximum
Heart rate >120/min

Characteristics of cardiac edema:

Dependent, pitting edema — ankles/feet during the day, sacral if bedridden
Bilateral and symmetrical
Associated with elevated JVP, hepatomegaly, ascites (right HF)
Dyspnea, orthopnea, PND (left HF)
Worse in the evening, improves overnight
Warm periphery if high-output; cold, clammy if low-output
BNP/NT-proBNP elevated — key biomarker

142. Diagnostic Criteria for Edema Syndrome in Kidney Diseases

Features distinguishing renal edema:

Feature	Detail
Distribution	Periorbital (facial) edema prominent in the morning; later generalized
Character	Soft, pitting, may be massive (anasarca) in nephrotic syndrome
Timing	Morning periorbital puffiness is characteristic
Proteinuria	Always present (>3.5 g/24h in nephrotic; variable in nephritic)
Urine abnormalities	Hematuria, casts in nephritic; heavy proteinuria ± lipiduria in nephrotic
Hypoalbuminemia	Prominent in nephrotic syndrome
Hypertension	Common in nephritic syndrome
Renal function	May be normal or reduced (↑creatinine, ↑BUN)
Ascites, pleural effusion	Can occur in severe hypoalbuminemia

The absence of elevated JVP and absence of pulmonary congestion distinguish renal edema from cardiac edema.

143. Diagnostic Criteria for Nephrotic Syndrome

Classic Pentad (pathognomonic of glomerular disease):

Proteinuria >3.5 g/24 hours (or spot urine protein:creatinine ratio >3.5 mg/mg)
Hypoalbuminemia (<3.0 g/dL, often <2.5 g/dL)
Edema (periorbital, peripheral, ascites, pleural effusion, anasarca)
Hyperlipidemia (↑total cholesterol, ↑LDL, ↑VLDL, ↑triglycerides — due to increased hepatic lipoprotein synthesis)
Lipiduria (free fat, oval fat bodies, fatty casts on urinalysis — "Maltese cross" pattern under polarized light)

Additional features:

Hypercoagulability (loss of antithrombin III, protein C/S in urine → DVT, renal vein thrombosis)
Increased susceptibility to infection (loss of immunoglobulins)
Muehrcke's lines in nails (white transverse bands — sign of hypoalbuminemia)

Major causes: Minimal change disease (children), membranous nephropathy (adults), FSGS, diabetic nephropathy, amyloidosis, SLE.

— Comprehensive Clinical Nephrology, 7th Edition

144. Mechanisms of Edema Formation in Chronic Heart Failure

CHF edema is primarily hemodynamic (overflow) — driven by renal sodium and water retention:

Reduced cardiac output → decreased renal perfusion
Activation of RAAS → angiotensin II causes vasoconstriction and aldosterone release → Na⁺ and water retention
Increased ADH (vasopressin) secretion → free water retention → dilutional hyponatremia
Sympathetic activation → renal vasoconstriction → further Na⁺ retention
Elevated venous pressure → increased capillary hydrostatic pressure → fluid transudation into interstitium
Hepatic congestion → reduced albumin synthesis → lower oncotic pressure (contributes in severe CHF)
ANP/BNP resistance — although secreted in response to volume overload, the kidney becomes relatively resistant to their natriuretic effects in advanced CHF

Result: Dependent pitting edema (ankles → legs → sacrum), pleural effusion, ascites, hepatomegaly (right HF); pulmonary edema, orthopnea (left HF).

— Harrison's Principles of Internal Medicine 22E; Comprehensive Clinical Nephrology, 7th Edition

145. Mechanism of Edema Formation in Nephritic Syndrome

Nephritic syndrome edema is primarily inflammatory/volume-overload in mechanism, distinct from nephrotic syndrome:

Direct renal inflammation (glomerulonephritis) → reduced GFR
Decreased GFR → reduced sodium and water excretion → primary sodium and water retention (overfill mechanism)
Expanded ECF volume → elevated capillary hydrostatic pressure → edema
Hypertension develops due to volume expansion
Proteinuria is present but usually <3.5 g/24h — hypoalbuminemia is mild or absent
Hematuria and RBC casts — hallmark of glomerular inflammation

Key features distinguishing nephritic from nephrotic edema:

Edema is less severe (typically periorbital + mild peripheral)
Hypertension is prominent (vs. nephrotic where BP may be low/normal)
Hematuria + RBC casts (vs. predominantly proteinuria + lipiduria)
No significant hypoalbuminemia
Oliguria common

Classic causes: Post-streptococcal GN, IgA nephropathy, lupus nephritis, anti-GBM disease.

146. Mechanisms of Edema Formation in Liver Cirrhosis and Portal Hypertension

Multiple interacting mechanisms:

Portal hypertension → increased hydrostatic pressure in splanchnic and mesenteric capillaries → ascites (predominant manifestation)
Decreased albumin synthesis (damaged hepatocytes) → hypoalbuminemia → reduced plasma oncotic pressure → fluid transudation
Splanchnic vasodilation (mediated by nitric oxide, prostacyclin) → peripheral arterial vasodilation → reduced effective circulating volume → "arterial underfilling"
Activation of RAAS and SNS → renal sodium and water retention → secondary hyperaldosteronism
Elevated ADH → dilutional hyponatremia + water retention
Reduced hepatic inactivation of aldosterone → further Na⁺ retention (hyperaldosteronism)
Lymphatic overflow — increased hepatic and splanchnic lymph production exceeds lymphatic drainage capacity → ascites

Result: Ascites (fluid in peritoneal cavity) is the hallmark; peripheral edema develops as portal hypertension and hypoalbuminemia worsen. Hepatic hydrothorax (usually right-sided) also occurs via diaphragmatic defects.

— Katzung's Basic and Clinical Pharmacology 16th Edition; Comprehensive Clinical Nephrology, 7th Edition

147. Laboratory Markers for Diagnosing the Causes of Edema

Test	Cardiac Edema	Nephrotic	Nephritic	Hepatic/Cirrhosis
BNP/NT-proBNP	↑↑ (key marker)	Normal	Normal/↑	May ↑
Serum albumin	Normal or ↓ (late)	↓↓ (<2.5 g/dL)	Normal/mild ↓	↓↓
Urine protein	Trace	>3.5 g/24h	1–3.5 g/24h	Trace
Urine sediment	Normal	Lipid casts, oval fat bodies	RBC casts, granular casts	Normal
Serum cholesterol	Normal	↑↑	Normal	↓ (late)
Serum creatinine	↑ (prerenal or cardiorenal)	Normal early	↑	↑ (hepatorenal)
Liver enzymes (AST/ALT/GGT)	↑ (congestive hepatopathy)	Normal	Normal	↑↑
PT/INR	Normal	Normal	Normal	↑ (synthetic dysfunction)
Serum complement (C3/C4)	Normal	Normal	↓ (post-strep GN, lupus)	Normal
ASLO (anti-streptolysin O)	Normal	Normal	↑ (post-strep)	Normal
ANA/anti-dsDNA	Normal	—	↑ (lupus nephritis)	Normal
Urine Na⁺	Low (<20 mEq/L)	Low	Variable	Very low (<10 mEq/L)

148. Principles of Treatment of Acute and Chronic Circulatory Failure

Acute Circulatory Failure (Shock):

General:

Secure airway, supplemental O₂, IV access
Hemodynamic monitoring (BP, HR, urine output, CVP, lactate)

By type:

Hypovolemic: IV fluid resuscitation (crystalloids first; blood products for hemorrhage)
Cardiogenic: cautious fluids, inotropes (dobutamine, milrinone), vasopressors (norepinephrine), treat underlying cause (PCI for MI, IABP, mechanical circulatory support)
Distributive (septic): IV fluids + vasopressors (norepinephrine first-line), antibiotics, source control
Anaphylactic: Epinephrine IM (first-line), antihistamines, steroids, airway management
Obstructive: Treat cause (thrombolytics/embolectomy for PE, pericardiocentesis for tamponade, needle decompression for tension pneumothorax)

Chronic Heart Failure:

Pharmacological (HFrEF — evidence-based "quadruple therapy"):

ACE inhibitor/ARB or ARNI (sacubitril-valsartan) — reduce mortality, inhibit RAAS
Beta-blocker (carvedilol, bisoprolol, metoprolol succinate) — reduce mortality, anti-remodeling
Mineralocorticoid receptor antagonist (spironolactone/eplerenone) — reduce mortality
SGLT2 inhibitor (dapagliflozin, empagliflozin) — reduce hospitalization and CV death

For symptom control:

Loop diuretics (furosemide) — reduce fluid overload, relieve dyspnea/edema
Digoxin — reduces hospitalizations in HFrEF
Sodium restriction (<2 g/day), fluid restriction in hyponatremia

Device therapy: ICD (sudden death prevention in EF <35%), CRT (cardiac resynchronization in LBBB + EF <35%), LVAD as bridge or destination therapy.

JOINT DISEASES (Questions 149–161)

149. Classification of Joint Diseases

I. Inflammatory arthritides:

Crystal-induced: Gout (monosodium urate), pseudogout (CPPD), hydroxyapatite disease
Autoimmune/Connective tissue: Rheumatoid arthritis, SLE, systemic sclerosis, dermatomyositis, Sjögren's syndrome
Spondyloarthropathies (seronegative): Ankylosing spondylitis, psoriatic arthritis, reactive arthritis (Reiter's), IBD-associated arthritis
Systemic arthritis of childhood: Still's disease (sJIA), pauciarticular JIA, polyarticular JIA
Septic arthritis (bacterial, viral, fungal)

II. Degenerative arthritis:

Osteoarthritis (primary and secondary)

III. Metabolic arthritis:

Gout, pseudogout, ochronosis, hemochromatosis

IV. Periarticular disorders:

Bursitis, tendinitis, fibromyalgia, enthesitis

V. Systemic diseases with joint involvement:

SLE, vasculitis, sarcoidosis, hemophilia, malignancy

150. Diagnostic Criteria for Rheumatic Polyarthritis (Acute Rheumatic Fever — Jones Criteria)

Major criteria:

Carditis (clinical or subclinical/echocardiographic)
Polyarthritis (migratory, affecting large joints)
Chorea (Sydenham's chorea)
Erythema marginatum
Subcutaneous nodules

Minor criteria:

Fever (≥38.5°C high-risk; ≥38°C low-risk populations)
Elevated ESR (≥60 mm/h high-risk; ≥30 mm/h low-risk) or CRP (≥3.0 mg/dL)
Prolonged PR interval on ECG
Polyarthralgia (only if arthritis not used as major criterion)

Evidence of preceding streptococcal infection:

Elevated/rising ASLO or other streptococcal antibodies
Positive throat culture or rapid strep test

Diagnosis requires: 2 major criteria OR 1 major + 2 minor criteria + evidence of preceding GAS infection.

Characteristic features of rheumatic arthritis:

Migratory — moves from joint to joint
Exquisitely tender, hot, swollen large joints (knees, ankles, elbows, wrists)
Responds dramatically to aspirin/NSAIDs
Self-limiting (6–8 weeks), does NOT cause permanent joint damage (unlike RA)

151. Diagnostic Criteria for Rheumatoid Arthritis (2010 ACR/EULAR Criteria)

Score ≥6/10 confirms RA (in patients with ≥1 swollen joint unexplained by another diagnosis):

Domain	Score
Joint involvement
1 large joint	0
2–10 large joints	1
1–3 small joints	2
4–10 small joints	3
>10 joints (incl. ≥1 small joint)	5
Serology
Negative RF and negative ACPA	0
Low positive RF or low positive ACPA	2
High positive RF or high positive ACPA	3
Acute-phase reactants
Normal CRP and normal ESR	0
Abnormal CRP or abnormal ESR	1
Duration of symptoms
<6 weeks	0
≥6 weeks	1

Key clinical features:

Symmetrical polyarthritis, small joints (MCPs, PIPs, wrists) — characteristically spares DIPs
Morning stiffness >1 hour
Ulnar deviation, swan-neck/boutonnière deformities (late)
Rheumatoid nodules (20–30% of patients)
Systemic: fatigue, weight loss, low-grade fever
Extra-articular: pleuritis, pericarditis, vasculitis, Felty's syndrome, episcleritis, sicca

Laboratory: RF positive (~70–80%), ACPA (anti-CCP) positive (~70%, highly specific), elevated ESR/CRP, normocytic anemia of chronic disease, thrombocytosis.

— Goldman-Cecil Medicine; Harrison's Principles of Internal Medicine 22E

152. Diagnostic Criteria for Felty's Syndrome

Felty's syndrome is a triad complicating severe, long-standing seropositive RA:

Rheumatoid arthritis (usually severe, >10 years duration, seropositive — high-titer RF, often ACPA positive)
Splenomegaly
Neutropenia (absolute neutrophil count <2.0 × 10⁹/L)

Additional features:

Recurrent bacterial infections (due to neutropenia + functional abnormalities)
Leg ulcers (often refractory, particularly over tibial surface)
Lymphadenopathy
Weight loss, fatigue
Hyperpigmentation of exposed skin
Elevated LFTs (hepatomegaly)
HLA-DR4 strongly associated

Laboratory findings:

High-titer RF (virtually all)
Positive ANA in ~50%
Leukopenia with neutropenia
Thrombocytopenia in some
Anemia

Note: Requires exclusion of other causes of neutropenia/splenomegaly.

153. Diagnostic Criteria for Still's Disease (Adult-Onset Still's Disease — AOSD / Yamaguchi Criteria)

Yamaguchi Criteria (diagnosis requires ≥5 criteria, including ≥2 major):

Major criteria:

Fever ≥39°C, lasting ≥1 week (quotidian or double-quotidian spike pattern)
Arthralgia or arthritis lasting ≥2 weeks
Typical rash — salmon-pink/evanescent maculopapular rash (appears with fever, fades when afebrile)
Leukocytosis ≥10,000/μL with ≥80% granulocytes

Minor criteria:

Sore throat
Lymphadenopathy
Hepatomegaly or splenomegaly
Abnormal liver function tests (elevated AST/ALT/LDH)
Negative RF and ANA

Exclusion criteria (must exclude):

Infectious diseases (especially EBV, CMV)
Malignancies (especially lymphoma)
Other rheumatic diseases

Hallmark lab finding: Markedly elevated serum ferritin (often >10,000 ng/mL — highly characteristic; ferritin >3,000 is suggestive). Glycosylated ferritin fraction <20% (normal ~50–80%) is a useful marker.

Systemic features: Macrophage activation syndrome (MAS) is a life-threatening complication.

154. Diagnostic Criteria for Reiter's Syndrome (Reactive Arthritis)

The classic triad (present in only ~33%):

Arthritis — asymmetric, oligoarticular, lower limb large joints (knees, ankles, feet)
Urethritis (or cervicitis in women)
Conjunctivitis (or anterior uveitis)

Broader diagnostic criteria (European Spondylarthropathy Study Group):

Inflammatory arthritis (asymmetric oligoarthritis, predominantly lower limb) plus
Evidence of preceding infection: urogenital (Chlamydia trachomatis) or enteric (Salmonella, Shigella, Campylobacter, Yersinia) within 1–6 weeks of articular symptoms

Additional characteristic features:

Heel pain/enthesitis (Achilles tendinitis, plantar fasciitis)
Keratoderma blennorrhagica — hyperkeratotic skin lesions on palms/soles
Circinate balanitis — painless shallow ulcers on glans penis
Oral ulcers (painless)
Nail changes (onycholysis, subungual hyperkeratosis)
Dactylitis ("sausage digits")
Sacroiliitis on imaging
HLA-B27 positive (~60–80%)
Negative RF (seronegative)

155. Diagnostic Criteria for Systemic Lupus Erythematosus (2019 EULAR/ACR Classification Criteria)

Entry criterion: ANA titer ≥1:80 (on HEp-2 cells or equivalent positive test) — must be present.

Then score additive domains (total ≥10 points = SLE):

Domain	Criteria	Points
Constitutional	Fever	2
Hematologic	Leukopenia	3
	Thrombocytopenia	4
	Autoimmune hemolysis	4
Neuropsychiatric	Delirium	2
	Psychosis	3
	Seizure	5
Mucocutaneous	Non-scarring alopecia	2
	Oral ulcers	2
	Subacute or discoid lupus	4
	Acute cutaneous lupus (malar rash)	6
Serosal	Pleural or pericardial effusion	5
	Acute pericarditis	6
Musculoskeletal	Joint involvement	6
Renal	Proteinuria >0.5 g/24h	4
	Renal biopsy Class II or V lupus nephritis	8
	Renal biopsy Class III or IV lupus nephritis	10
Antiphospholipid antibodies	Anti-cardiolipin, anti-β2GPI, lupus anticoagulant	2
Complement proteins	Low C3 OR low C4	3
	Low C3 AND low C4	4
SLE-specific antibodies	Anti-dsDNA OR anti-Sm	6

Classic features (older 1997 ACR criteria, still clinically used):

Malar (butterfly) rash
Discoid rash
Photosensitivity
Oral ulcers
Non-scarring alopecia
Serositis (pleuritis, pericarditis)
Renal disorder (proteinuria, casts)
Neurologic disorder (seizures, psychosis)
Hematologic disorder (hemolytic anemia, leukopenia, lymphopenia, thrombocytopenia)
Immunologic (anti-dsDNA, anti-Sm, antiphospholipid Abs)
ANA positive

156. Diagnostic Criteria for Systemic Sclerosis (Scleroderma) — 2013 ACR/EULAR Criteria

Score ≥9 = SSc classification (entry criterion: skin thickening of fingers extends proximal to MCP joints)

Feature	Score
Skin thickening of fingers extending proximal to MCPs	9 (sufficient alone)
Puffy fingers	2
Fingertip lesions (pitting scars or digital tip ulcers)	2–3
Telangiectasia	2
Abnormal nailfold capillaries	2
Pulmonary arterial hypertension and/or ILD	2
Raynaud's phenomenon	3
SSc-related antibodies (anti-centromere, anti-Scl-70/topoisomerase I, anti-RNA pol III)	3

Clinical subtypes:

Limited cutaneous SSc (lcSSc): skin involvement distal to elbows/knees + face; CREST syndrome (Calcinosis, Raynaud's, Esophageal dysmotility, Sclerodactyly, Telangiectasia); anti-centromere antibodies; later PAH risk
Diffuse cutaneous SSc (dcSSc): widespread skin involvement including trunk; anti-Scl-70 (topoisomerase I); early ILD, renal crisis risk

157. Diagnostic Criteria for Dermatomyositis

Bohan and Peter Criteria (classic):

Symmetric proximal muscle weakness (shoulder and pelvic girdle)
Elevated muscle enzymes: CK, aldolase, LDH, AST, ALT
Myopathic changes on EMG: short-duration, low-amplitude polyphasic units; spontaneous fibrillations
Muscle biopsy: necrosis, degeneration, regeneration, perivascular inflammatory infiltrate; perifascicular atrophy (characteristic of DM)
Characteristic skin rashes:
- Heliotrope rash — violaceous discoloration of eyelids with periorbital edema
- Gottron's papules — erythematous papules over MCP/PIP joints (pathognomonic)
- Gottron's sign — erythematous rash over elbows, knees, medial malleoli
- V-sign (anterior chest), Shawl sign (posterior neck/shoulders)
- Mechanics' hands (hyperkeratosis, fissuring of lateral fingers)

Definite DM: rash + 3 of 4 other criteria Probable DM: rash + 2 of 4 other criteria

Additional features:

Dysphagia (pharyngeal/esophageal involvement)
ILD (anti-Jo-1 antibody — antisynthetase syndrome)
Calcinosis (especially juvenile DM)
Malignancy — 15–25% of adult DM associated with underlying cancer (ovarian, lung, GI, breast — screen all adult patients)

Antibodies: Anti-Jo-1 (antisynthetase), anti-Mi-2, anti-MDA5 (amyopathic DM + rapidly progressive ILD), anti-TIF1γ (cancer-associated DM)

158. Diagnostic Criteria for Deforming Osteoarthritis

ACR Clinical Criteria for OA of the Knee:

Knee pain + ≥3 of:
- Age >50
- Morning stiffness <30 minutes
- Crepitus on active motion
- Bony tenderness
- Bony enlargement
- No palpable warmth

ACR Clinical Criteria for OA of the Hand:

Hand pain/ache/stiffness + ≥3 of:
- Hard tissue enlargement ≥2 of 10 selected joints
- Hard tissue enlargement ≥2 DIP joints
- Fewer than 3 swollen MCP joints
- Deformity ≥1 of 10 selected joints

Radiographic features (Kellgren-Lawrence grading):

Grade 0: Normal
Grade 1: Possible osteophytes
Grade 2: Definite osteophytes, possible joint space narrowing
Grade 3: Moderate joint space narrowing, subchondral sclerosis
Grade 4: Large osteophytes, severe narrowing, subchondral cysts, deformity

Clinical features:

Pain worsens with use, relieved by rest (in contrast to inflammatory arthritis)
Morning stiffness <30 minutes (vs. >1 hour in RA)
Heberden's nodes (DIP joints) and Bouchard's nodes (PIP joints) — bony enlargements
DIP joint involvement (unlike RA which spares DIPs)
No systemic features
Normal inflammatory markers (ESR, CRP), negative RF

159. Diagnostic Criteria for Gout

2015 ACR/EULAR Classification Criteria:

Step 1 — Entry criterion: At least one episode of swelling, pain, or tenderness in a peripheral joint/bursa.

Step 2 — Sufficient criterion (if present, classify as gout without further scoring):

Presence of MSU crystals in symptomatic joint/bursa OR tophus with MSU crystals confirmed.

Step 3 — Scoring (if crystal confirmation not available):

Domain	Category	Score
Symptom pattern (ever)	Ankle/midfoot (monoarticular)	1
	1st MTP joint involvement	2
Characteristics of episodes	Erythema, can't bear touch, inability to walk	1 each
Time course	≥2 typical episodes (rapid onset, resolution ≤14 days)	2
Clinical evidence of tophus	Present	4
Serum urate	<4 mg/dL	-4
	6–<8 mg/dL	2
	8–<10 mg/dL	3
	≥10 mg/dL	4
Synovial fluid analysis	MSU negative	-2
Imaging	Urate deposition on US (double contour sign)	4
	Gout-related joint damage on CT	4

Score ≥8 = classified as gout

Classic presentation:

Acute monoarthritis of 1st MTP joint (podagra) — in >50% of first attacks
Excruciating pain, swelling, erythema, warmth, tenderness
Attacks often nocturnal, precipitated by alcohol, purine-rich foods, dehydration, surgery, diuretics
Tophi — deposits of monosodium urate in soft tissue (helix of ear, Achilles tendon, olecranon bursa, fingers)
Hyperuricemia (though may be normal during acute attack)
Polarized light microscopy of synovial fluid: negatively birefringent needle-shaped MSU crystals

160. Role of Glucocorticosteroids in the Treatment of Rheumatoid Arthritis

Indications:

Bridge therapy — rapid symptom control while waiting for DMARDs (which take weeks to months to work)
Disease flares — short courses during acute exacerbations
Adjunct to DMARDs — low-dose long-term therapy as a disease-modifying agent in some patients
Systemic extra-articular manifestations — vasculitis, serositis, scleritis

Mechanisms of benefit in RA:

Potent anti-inflammatory effects (inhibit PLA2, COX expression, cytokine production — IL-1, TNF, IL-6)
Immunosuppressive (reduce lymphocyte trafficking, DC function)
Radiographic data suggest they slow joint erosion (disease-modifying effect at low doses)

Regimens:

Low-dose maintenance: Prednisolone ≤7.5 mg/day — used alongside DMARDs to reduce joint inflammation and slow radiographic progression
Bridge therapy: 20–40 mg prednisone/day, tapering over weeks
High-dose or IV pulse (methylprednisolone 500–1000 mg IV): for severe systemic disease/vasculitis

Adverse effects (major concern with long-term use):

Osteoporosis (all patients on >7.5 mg/day for >3 months should receive calcium, vitamin D, and consider bisphosphonates)
Adrenal suppression
Diabetes mellitus / hyperglycemia
Hypertension
Cataracts, glaucoma
Cushingoid features
Increased infection risk
Avascular necrosis of bone

Current position: Glucocorticoids are recommended for short-term or bridge use; long-term use should be minimized to the lowest effective dose due to toxicity. The 2022 ACR guidelines recommend tapering to discontinuation when possible.

161. Use of Cytostatics (Cytotoxic Agents / Non-biologic DMARDs) in the Treatment of Rheumatoid Arthritis

Methotrexate (MTX) — First-line DMARD:

Gold standard of RA treatment; cornerstone of all guidelines
Mechanism: Inhibits dihydrofolate reductase → reduces purine synthesis and adenosine-mediated anti-inflammatory effects; also inhibits cytokine production
Dose: 15–25 mg/week (oral or SC); always co-prescribed with folic acid (5 mg/week) to reduce toxicity
Onset: 6–12 weeks
Efficacy: Reduces joint inflammation, prevents radiographic erosions, improves functional outcomes, reduces mortality
Toxicity: Hepatotoxicity (monitor LFTs; contraindicated in liver disease/heavy alcohol use), myelosuppression, mucositis, nausea, pulmonary toxicity (MTX pneumonitis — rare but serious), teratogenicity (absolutely contraindicated in pregnancy)

Leflunomide:

Inhibits dihydroorotate dehydrogenase → pyrimidine synthesis inhibition → reduces T-cell proliferation
Efficacy comparable to MTX; used as alternative or add-on
Toxicity: hepatotoxicity, diarrhea, hypertension, teratogenicity (long half-life — requires cholestyramine washout before pregnancy)

Sulfasalazine:

Anti-inflammatory and immunomodulatory; used in early/mild RA and combination therapy
Toxicity: GI intolerance, hepatotoxicity, blood dyscrasias, hypersensitivity

Hydroxychloroquine (antimalarial):

Least toxic DMARD; used in mild disease or combination ("triple therapy")
Requires ophthalmologic monitoring (retinopathy)

Azathioprine:

Purine synthesis inhibitor; used when MTX is contraindicated or as second-line
Toxicity: myelosuppression, hepatotoxicity, lymphoma risk

Cyclophosphamide:

Reserved for severe extra-articular RA (vasculitis, severe systemic disease)
Significant toxicity: hemorrhagic cystitis, myelosuppression, gonadal toxicity, malignancy risk (bladder cancer, lymphoma)

Combination strategies:

MTX + leflunomide: more effective, monitor closely for hepatotoxicity
Triple therapy: MTX + sulfasalazine + hydroxychloroquine — comparable to biologic therapy in some studies
MTX + biologic (TNF inhibitors, abatacept, tocilizumab, JAK inhibitors): standard for moderate-to-severe RA failing MTX monotherapy

Sources: Comprehensive Clinical Nephrology 7th Ed; Brenner and Rector's The Kidney; Harrison's Principles of Internal Medicine 22E; Goldman-Cecil Medicine; Katzung's Basic and Clinical Pharmacology 16th Ed; Braunwald's Heart Disease

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