ls /home/daytona/workspace/ 2>/dev/null && echo "OK"

mkdir -p /home/daytona/workspace/arthritis-pdf && python3 -c "from reportlab.lib…

~/arthritis-pdf/generate_arthritis_pdf.py

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import cm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    HRFlowable, PageBreak, KeepTogether
)
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY
from reportlab.platypus import ListFlowable, ListItem

OUTPUT = "/home/daytona/workspace/arthritis-pdf/Arthritis_Clinical_Overview.pdf"

# ── Colour palette ──────────────────────────────────────────────────────────
DARK_BLUE   = colors.HexColor("#1A3A5C")
MED_BLUE    = colors.HexColor("#2E6DA4")
LIGHT_BLUE  = colors.HexColor("#D6E8F7")
ACCENT      = colors.HexColor("#E84040")
GOLD        = colors.HexColor("#F5A623")
LIGHT_GREY  = colors.HexColor("#F2F4F7")
MID_GREY    = colors.HexColor("#B0BEC5")
WHITE       = colors.white
BLACK       = colors.black

# ── Styles ───────────────────────────────────────────────────────────────────
base = getSampleStyleSheet()

def S(name, parent="Normal", **kw):
    return ParagraphStyle(name, parent=base[parent], **kw)

styles = {
    "cover_title": S("cover_title", "Title",
        fontSize=34, textColor=WHITE, leading=42, alignment=TA_CENTER, spaceAfter=6),
    "cover_sub":   S("cover_sub", "Normal",
        fontSize=14, textColor=colors.HexColor("#AED6F1"), alignment=TA_CENTER, spaceAfter=4),
    "cover_note":  S("cover_note", "Normal",
        fontSize=10, textColor=colors.HexColor("#AED6F1"), alignment=TA_CENTER),
    "h1": S("h1", "Heading1",
        fontSize=18, textColor=WHITE, leading=24, spaceBefore=0, spaceAfter=0,
        leftIndent=0),
    "h2": S("h2", "Heading2",
        fontSize=13, textColor=DARK_BLUE, leading=18, spaceBefore=10, spaceAfter=4,
        borderPad=4),
    "h3": S("h3", "Heading3",
        fontSize=11, textColor=MED_BLUE, leading=15, spaceBefore=6, spaceAfter=3),
    "body": S("body", "Normal",
        fontSize=9.5, leading=14, spaceAfter=4, alignment=TA_JUSTIFY),
    "bullet": S("bullet", "Normal",
        fontSize=9.5, leading=13, leftIndent=14, spaceAfter=2),
    "table_hdr": S("table_hdr", "Normal",
        fontSize=9, textColor=WHITE, leading=12, alignment=TA_CENTER),
    "table_cell": S("table_cell", "Normal",
        fontSize=8.5, leading=12, alignment=TA_LEFT),
    "table_cell_c": S("table_cell_c", "Normal",
        fontSize=8.5, leading=12, alignment=TA_CENTER),
    "caption": S("caption", "Normal",
        fontSize=8, textColor=MID_GREY, alignment=TA_CENTER, spaceAfter=6),
    "key_point": S("key_point", "Normal",
        fontSize=9, leading=13, textColor=DARK_BLUE,
        leftIndent=10, rightIndent=10, spaceAfter=3),
    "footer": S("footer", "Normal",
        fontSize=7.5, textColor=MID_GREY, alignment=TA_CENTER),
}

PAGE_W, PAGE_H = A4
MARGIN = 2.0 * cm

# ── Helper builders ──────────────────────────────────────────────────────────
def section_header(title, subtitle=""):
    """Coloured banner for a major section."""
    data = [[Paragraph(f"<b>{title}</b>", styles["h1"])]]
    t = Table(data, colWidths=[PAGE_W - 2*MARGIN])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), DARK_BLUE),
        ("ROUNDEDCORNERS", [6,6,6,6]),
        ("TOPPADDING",    (0,0), (-1,-1), 10),
        ("BOTTOMPADDING", (0,0), (-1,-1), 10),
        ("LEFTPADDING",   (0,0), (-1,-1), 14),
    ]))
    elems = [t]
    if subtitle:
        elems.append(Paragraph(subtitle, styles["body"]))
    elems.append(Spacer(1, 6))
    return elems

def h2(text):
    return [Paragraph(text, styles["h2"]), HRFlowable(width="100%", thickness=1,
            color=MED_BLUE, spaceAfter=4)]

def h3(text):
    return [Paragraph(text, styles["h3"])]

def body(text):
    return [Paragraph(text, styles["body"])]

def bullets(items):
    return [Paragraph(f"• {i}", styles["bullet"]) for i in items]

def spacer(h=6):
    return [Spacer(1, h)]

def key_box(items, title="Key Points"):
    content = [Paragraph(f"<b>{title}</b>", styles["key_point"])]
    for i in items:
        content.append(Paragraph(f"◆  {i}", styles["key_point"]))
    t = Table([[content]], colWidths=[PAGE_W - 2*MARGIN])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), LIGHT_BLUE),
        ("ROUNDEDCORNERS", [6,6,6,6]),
        ("TOPPADDING",    (0,0), (-1,-1), 8),
        ("BOTTOMPADDING", (0,0), (-1,-1), 8),
        ("LEFTPADDING",   (0,0), (-1,-1), 10),
        ("RIGHTPADDING",  (0,0), (-1,-1), 10),
        ("BOX", (0,0), (-1,-1), 1, MED_BLUE),
    ]))
    return [t, Spacer(1, 6)]

def make_table(headers, rows, col_widths=None):
    avail = PAGE_W - 2*MARGIN
    if col_widths is None:
        col_widths = [avail / len(headers)] * len(headers)
    hdr_row = [Paragraph(f"<b>{h}</b>", styles["table_hdr"]) for h in headers]
    data = [hdr_row]
    for row in rows:
        data.append([Paragraph(str(c), styles["table_cell"]) for c in row])
    t = Table(data, colWidths=col_widths, repeatRows=1)
    style = TableStyle([
        ("BACKGROUND",    (0,0), (-1,0),  DARK_BLUE),
        ("ROWBACKGROUNDS",(0,1), (-1,-1), [WHITE, LIGHT_GREY]),
        ("GRID",          (0,0), (-1,-1), 0.4, MID_GREY),
        ("TOPPADDING",    (0,0), (-1,-1), 5),
        ("BOTTOMPADDING", (0,0), (-1,-1), 5),
        ("LEFTPADDING",   (0,0), (-1,-1), 6),
        ("RIGHTPADDING",  (0,0), (-1,-1), 6),
        ("VALIGN",        (0,0), (-1,-1), "TOP"),
    ])
    t.setStyle(style)
    return [t, Spacer(1, 8)]

# ── Page callbacks ────────────────────────────────────────────────────────────
def on_page(canvas, doc):
    canvas.saveState()
    # Top blue bar
    canvas.setFillColor(DARK_BLUE)
    canvas.rect(0, PAGE_H - 0.7*cm, PAGE_W, 0.7*cm, fill=1, stroke=0)
    canvas.setFillColor(WHITE)
    canvas.setFont("Helvetica", 7)
    canvas.drawCentredString(PAGE_W/2, PAGE_H - 0.5*cm, "ARTHRITIS — Clinical Overview")
    # Bottom bar
    canvas.setFillColor(LIGHT_GREY)
    canvas.rect(0, 0, PAGE_W, 1.0*cm, fill=1, stroke=0)
    canvas.setFillColor(MID_GREY)
    canvas.setFont("Helvetica", 7)
    canvas.drawString(MARGIN, 0.35*cm, "Sources: Robbins & Kumar Basic Pathology | Textbook of Family Medicine 9e | Goldman-Cecil Medicine | Rosen's Emergency Medicine | Firestein & Kelley's Rheumatology")
    canvas.drawRightString(PAGE_W - MARGIN, 0.35*cm, f"Page {doc.page}")
    canvas.restoreState()

def cover_page():
    from reportlab.platypus import Frame, BaseDocTemplate
    # We'll fake a cover with a coloured table
    elems = []
    # Blue banner fill
    cover_data = [[
        Paragraph("<b>ARTHRITIS</b>", styles["cover_title"]),
    ]]
    ct = Table(cover_data, colWidths=[PAGE_W - 2*MARGIN])
    ct.setStyle(TableStyle([
        ("BACKGROUND",    (0,0), (-1,-1), DARK_BLUE),
        ("TOPPADDING",    (0,0), (-1,-1), 40),
        ("BOTTOMPADDING", (0,0), (-1,-1), 10),
        ("LEFTPADDING",   (0,0), (-1,-1), 20),
        ("RIGHTPADDING",  (0,0), (-1,-1), 20),
        ("ROUNDEDCORNERS",[8,8,8,8]),
    ]))
    elems.append(ct)
    sub_data = [[Paragraph("Clinical Deep-Dive: All Types, Pathology, Diagnosis & Treatment", styles["cover_sub"])]]
    st = Table(sub_data, colWidths=[PAGE_W - 2*MARGIN])
    st.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), MED_BLUE),
        ("TOPPADDING",    (0,0), (-1,-1), 12),
        ("BOTTOMPADDING", (0,0), (-1,-1), 12),
        ("ROUNDEDCORNERS",[0,0,8,8]),
    ]))
    elems.append(st)
    elems.append(Spacer(1, 16))

    # Type overview boxes
    types = [
        ("1", "Osteoarthritis",       "Degenerative",      GOLD),
        ("2", "Rheumatoid Arthritis", "Autoimmune",        ACCENT),
        ("3", "Gout",                 "Crystal",           colors.HexColor("#27AE60")),
        ("4", "Spondyloarthritis",    "Seronegative",      MED_BLUE),
        ("5", "Psoriatic Arthritis",  "Seronegative SpA",  colors.HexColor("#8E44AD")),
        ("6", "Reactive Arthritis",   "Post-infectious",   colors.HexColor("#E67E22")),
        ("7", "Septic Arthritis",     "Infectious/Emergency", ACCENT),
    ]
    box_rows = []
    for num, name, tag, col in types:
        box_rows.append([
            Paragraph(f"<b>{num}</b>", ParagraphStyle("n", fontSize=18, textColor=WHITE, alignment=TA_CENTER)),
            Paragraph(f"<b>{name}</b><br/><font size=8 color='#FFFFFF'>{tag}</font>",
                      ParagraphStyle("t", fontSize=11, textColor=WHITE, leading=15)),
        ])
    for i, (num, name, tag, col) in enumerate(types):
        row_data = [[
            Paragraph(f"<b>{i+1}</b>", ParagraphStyle("nn", fontSize=16, textColor=WHITE, alignment=TA_CENTER)),
            Paragraph(f"<b>{name}</b><br/><font size=8>{tag}</font>",
                      ParagraphStyle("tt", fontSize=11, textColor=WHITE, leading=15)),
        ]]
        rt = Table(row_data, colWidths=[1.2*cm, PAGE_W - 2*MARGIN - 1.2*cm - 0.2*cm])
        rt.setStyle(TableStyle([
            ("BACKGROUND",    (0,0), (-1,-1), col),
            ("TOPPADDING",    (0,0), (-1,-1), 8),
            ("BOTTOMPADDING", (0,0), (-1,-1), 8),
            ("LEFTPADDING",   (0,0), (-1,-1), 10),
            ("ROUNDEDCORNERS",[6,6,6,6]),
        ]))
        elems.append(rt)
        elems.append(Spacer(1, 5))

    elems.append(Spacer(1, 20))
    note_data = [[Paragraph(
        "Sources: Robbins & Kumar Basic Pathology • Textbook of Family Medicine 9e • Goldman-Cecil Medicine • Rosen's Emergency Medicine • Firestein & Kelley's Textbook of Rheumatology",
        styles["caption"])]]
    nt = Table(note_data, colWidths=[PAGE_W - 2*MARGIN])
    nt.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), LIGHT_GREY),
        ("TOPPADDING",    (0,0), (-1,-1), 8),
        ("BOTTOMPADDING", (0,0), (-1,-1), 8),
        ("BOX", (0,0), (-1,-1), 0.5, MID_GREY),
    ]))
    elems.append(nt)
    elems.append(PageBreak())
    return elems

# ── Content ───────────────────────────────────────────────────────────────────
def build_content():
    E = []

    # ── COVER ─────────────────────────────────────────────────────────────────
    E += cover_page()

    # ── 1. OSTEOARTHRITIS ─────────────────────────────────────────────────────
    E += section_header("1. Osteoarthritis (OA)", "Degenerative Joint Disease — Most Common Arthritis")
    E += key_box([
        "Most common form of arthritis; affects ~20% of U.S. population.",
        "Primarily degenerative — cartilage breakdown with secondary inflammation.",
        "Prevalence rises exponentially after age 50; ~40% of people >70 are affected.",
        "NSAIDs (not COX-2 inhibitors alone) are first-line pharmacologic treatment.",
    ])
    E += h2("Epidemiology & Classification")
    E += body("OA occurs about equally in men and women ages 45–55, but is more common in women after 55. "
              "It is found radiographically in almost all 75-year-olds, most of whom are asymptomatic.")
    E += make_table(
        ["Type", "Description", "Examples"],
        [
            ["Primary (Idiopathic)", "Insidious onset; aging phenomenon; oligoarticular", "Knee, hip, lumbar spine OA in the elderly"],
            ["Hereditary", "Collagen gene defects; inflammatory hand OA runs in families", "Heberden nodes, Bouchard nodes in women"],
            ["Secondary", "Prior cartilage damage from identifiable cause", "Post-trauma, obesity, hemochromatosis, RA, gout, CPPD, acromegaly, neuropathy"],
        ],
        col_widths=[3.5*cm, 7*cm, 6.5*cm]
    )

    E += h2("Pathogenesis")
    E += body("OA stems from <b>biomechanical stress</b> on articular cartilage, with genetic factors (GDF5, RUNX2, SMAD3 loci) amplifying risk. "
              "The process evolves in three stages:")
    E += bullets([
        "<b>Stage 1 – Chondrocyte Injury:</b> Genetic/biomechanical insults damage Type II collagen and proteoglycans in articular cartilage.",
        "<b>Stage 2 – Early OA:</b> Chondrocytes proliferate and release BMP (repair attempt). MMPs degrade collagen and proteoglycans; PGE₂, NO, TNF drive further damage — degradation exceeds repair.",
        "<b>Stage 3 – Late OA:</b> Chondrocyte dropout and apoptosis, subchondral bone sclerosis and cysts, osteophyte formation, loose bodies in joint space.",
    ])

    E += h2("Clinical Features")
    E += make_table(
        ["Feature", "Details"],
        [
            ["Onset", "Insidious; pain worsens with activity, relieved by rest"],
            ["Morning stiffness", "< 30 minutes (key distinction from RA)"],
            ["Joint involvement", "Weight-bearing: knees, hips, lumbar/cervical spine, 1st MTP, DIP/PIP of hands"],
            ["Heberden nodes", "Bony enlargement at DIP joints (osteophytes)"],
            ["Bouchard nodes", "Bony enlargement at PIP joints"],
            ["Crepitus", "Grating sensation on joint movement"],
            ["Systemic features", "ABSENT — OA is purely articular"],
            ["Radiographic findings", "Joint space narrowing, osteophytes, subchondral sclerosis, subchondral cysts"],
        ],
        col_widths=[5*cm, 12*cm]
    )

    E += h2("Investigations")
    E += bullets([
        "X-ray: joint space narrowing, osteophytes, subchondral sclerosis/cysts — most important investigation",
        "Serology: RF and ANA negative; no specific OA biomarker",
        "Synovial fluid: non-inflammatory (WBC < 2,000/mm³); no crystals",
        "MRI: best for early cartilage damage (not routine in most cases)",
    ])

    E += h2("Treatment")
    E += make_table(
        ["Category", "Intervention"],
        [
            ["Non-pharmacologic", "Weight loss (reduces joint load), low-impact exercise (swimming, cycling), physiotherapy, quadriceps strengthening, assistive devices (cane, braces)"],
            ["Pharmacologic — 1st line", "NSAIDs (oral or topical for knee/hand); acetaminophen for mild pain"],
            ["Pharmacologic — adjuncts", "Intra-articular corticosteroids (short-term flare relief); intra-articular hyaluronic acid (controversial)"],
            ["Surgical", "Joint replacement (arthroplasty) for severe, refractory disease unresponsive to conservative measures"],
        ],
        col_widths=[4.5*cm, 12.5*cm]
    )
    E += spacer(8)

    # ── 2. RHEUMATOID ARTHRITIS ───────────────────────────────────────────────
    E += section_header("2. Rheumatoid Arthritis (RA)", "Chronic Systemic Autoimmune Inflammatory Disease")
    E += key_box([
        "Affects 1–2% of adults; female predominance 3:1; peak incidence ages 20–50.",
        "Symmetric synovitis with morning stiffness >1 hour is the hallmark.",
        ">70% of polyarticular RF-positive RA patients develop joint erosions within 2 years without treatment.",
        "Start DMARDs early — before irreversible joint destruction occurs.",
    ])

    E += h2("Pathogenesis")
    E += bullets([
        "<b>Genetic:</b> HLA-DRB1 'shared epitope' is the strongest genetic risk factor; higher concordance in monozygotic twins.",
        "<b>Trigger:</b> Unknown inciting event (possibly infectious or environmental) in a genetically susceptible host.",
        "<b>Pannus formation:</b> Synovial lining cells and subsynovial vessels proliferate → aggressive pannus invades cartilage and bone.",
        "<b>Immune cascade:</b> T-cell and B-cell activation; key cytokines TNF-α, IL-1, IL-6 drive inflammation and erosion.",
        "<b>Autoantibodies:</b> Rheumatoid factor (RF) targets IgG Fc; Anti-CCP (ACPA) — more specific, detectable years before symptoms.",
    ])

    E += h2("Clinical Features")
    E += make_table(
        ["System", "Manifestations"],
        [
            ["Articular (early)", "Symmetric synovitis of MCPs, PIPs, wrists; spares DIP joints"],
            ["Articular (late)", "Ulnar deviation, swan-neck/boutonnière deformities, Z-thumb; joint ankylosis"],
            ["Constitutional", "Fatigue, fever, weight loss, malaise (often precede joint symptoms)"],
            ["Rheumatoid nodules", "Subcutaneous; over pressure points (olecranon, fingers); indicate seropositive disease"],
            ["Pulmonary", "Interstitial lung disease, pleural effusion, pulmonary nodules, Caplan syndrome"],
            ["Cardiac", "Pericarditis, accelerated atherosclerosis (major cause of mortality), valvular disease"],
            ["Ocular", "Scleritis, episcleritis, sicca syndrome (secondary Sjögren's)"],
            ["Neurologic", "Atlantoaxial subluxation (C1–C2 instability → spinal cord compression risk), peripheral neuropathy"],
            ["Haematologic", "Anaemia of chronic disease, Felty syndrome (RA + splenomegaly + neutropenia)"],
        ],
        col_widths=[4.5*cm, 12.5*cm]
    )

    E += h2("ACR 1987 Diagnostic Criteria (≥4 of 7, symptoms ≥6 weeks)")
    E += make_table(
        ["#", "Criterion", "Definition"],
        [
            ["1", "Morning stiffness", "In and around joints; ≥1 hour before maximal improvement"],
            ["2", "Arthritis of ≥3 joint areas", "Soft-tissue swelling or fluid in ≥3 joints"],
            ["3", "Arthritis of hand joints", "Wrists, MCPs, or PIPs involved"],
            ["4", "Symmetric arthritis", "Simultaneous bilateral involvement"],
            ["5", "Rheumatoid nodules", "Subcutaneous nodules over bony prominences"],
            ["6", "Serum RF positive", "Positive by any method in <5% of normal controls"],
            ["7", "Radiographic changes", "Erosions or periarticular osteopenia on hand/wrist X-ray"],
        ],
        col_widths=[0.8*cm, 5*cm, 11.2*cm]
    )

    E += h2("Investigations")
    E += bullets([
        "RF: positive in ~80% of RA; not specific (also positive in SLE, Sjögren's, infections, elderly)",
        "Anti-CCP (ACPA): ~95% specific for RA; detectable years before clinical disease",
        "Elevated ESR and CRP — reflect inflammatory activity",
        "FBC: normocytic anaemia, thrombocytosis in active disease",
        "Synovial fluid: inflammatory (WBC >2,000/mm³, often >50,000); no crystals",
        "X-ray hands/feet: periarticular osteopenia → marginal erosions → joint space narrowing",
        "MRI/Ultrasound: detect early synovitis and erosions before X-ray changes",
    ])

    E += h2("Treatment — Treat-to-Target Strategy")
    E += make_table(
        ["Category", "Agents", "Notes"],
        [
            ["Symptomatic", "NSAIDs, corticosteroids (oral/intra-articular)", "Bridging only; not disease-modifying"],
            ["Conventional DMARDs (csDMARDs)", "Methotrexate (1st-line), hydroxychloroquine, sulfasalazine, leflunomide", "MTX is anchor drug; combinations used (triple therapy)"],
            ["Biologic DMARDs — anti-TNF", "Etanercept, adalimumab, infliximab, certolizumab, golimumab", "For inadequate response to csDMARDs"],
            ["Biologic DMARDs — other", "Tocilizumab (IL-6 inhibitor), rituximab (B-cell), abatacept (T-cell co-stim)", "Alternative biologics depending on profile"],
            ["Targeted synthetic DMARDs", "Tofacitinib, baricitinib, upadacitinib (JAK inhibitors)", "Oral; used when biologics fail or not tolerated"],
        ],
        col_widths=[3.5*cm, 6*cm, 7.5*cm]
    )
    E.append(PageBreak())

    # ── 3. GOUT ──────────────────────────────────────────────────────────────
    E += section_header("3. Gout (Crystal Arthropathy)", "Monosodium Urate Crystal Deposition Disease")
    E += key_box([
        "Primarily affects men 40–60 years and postmenopausal women.",
        "Hyperuricemia (usually >8 mg/dL) is the underlying abnormality — but asymptomatic hyperuricemia is not a disease.",
        "Definitive diagnosis: needle-shaped, negatively birefringent crystals on polarized light microscopy.",
        "First MTP joint (podagra) involved in 50% of initial attacks; eventually in 75–90% of patients.",
    ])

    E += h2("Pathophysiology")
    E += make_table(
        ["Mechanism", "Details"],
        [
            ["Reduced excretion (90%)", "Renal underexcretion of urate; genetic predisposition + thiazides, low-dose aspirin, cyclosporine, renal failure"],
            ["Overproduction (10%)", "Inborn errors (HGPRT deficiency — Lesch-Nyhan), high purine diet, myeloproliferative disorders, tumour lysis"],
            ["Crystal deposition", "MSU crystals form in cooler peripheral joints → phagocytosed by neutrophils → IL-1β release → acute intense inflammation"],
            ["Tophi", "Chronic urate deposits in soft tissue, cartilage, bone, ear pinnae; indicate years of uncontrolled hyperuricemia"],
        ],
        col_widths=[4.5*cm, 12.5*cm]
    )

    E += h2("Clinical Stages")
    E += make_table(
        ["Stage", "Features"],
        [
            ["Asymptomatic hyperuricemia", "Elevated uric acid; no symptoms; typically takes ~20 years before first attack"],
            ["Acute gouty arthritis", "Sudden severe monoarticular pain (often nocturnal); exquisite tenderness; swelling, warmth, erythema; self-limited in days–weeks"],
            ["Intercritical gout", "Symptom-free intervals; attacks become more frequent and prolonged over time"],
            ["Chronic tophaceous gout", "Persistent hyperuricemia → tophi; chronic destructive arthritis; renal complications (urate nephropathy, uric acid stones)"],
        ],
        col_widths=[5*cm, 12*cm]
    )

    E += h2("Diagnosis")
    E += bullets([
        "<b>Definitive:</b> Needle-shaped, negatively birefringent monosodium urate crystals on polarized light microscopy of synovial fluid or tophi material",
        "<b>Presumptive:</b> Clinical features + hyperuricemia + rapid response to colchicine/NSAIDs",
        "Serum uric acid: usually >8 mg/dL (note: may be normal during acute attack)",
        "Joint aspiration: cloudy fluid, high WBC (polymorphonuclear predominance)",
        "X-ray (late disease): punched-out erosions with overhanging edges ('rat bite' erosions), tophi calcifications",
        "Note: In women and elderly, gout may be <b>polyarticular</b> and mimic RA; tophi may be mistaken for rheumatoid nodules",
    ])

    E += h2("Treatment")
    E += make_table(
        ["Phase", "Treatment", "Notes"],
        [
            ["Acute attack", "NSAIDs (indomethacin, naproxen), colchicine, corticosteroids (oral/IA)", "Start within 24 hours of attack onset for best effect"],
            ["Urate-lowering therapy (ULT)", "Allopurinol (xanthine oxidase inhibitor) — 1st line; Febuxostat; Probenecid (uricosuric)", "Target serum uric acid <6 mg/dL (<5 mg/dL in tophaceous gout)"],
            ["Prophylaxis during ULT initiation", "Low-dose colchicine or NSAID for 3–6 months", "Prevents mobilization flares as urate depots dissolve"],
            ["Dietary/lifestyle", "Reduce red meat, seafood, fructose-sweetened beverages, alcohol (especially beer); increase hydration", "Address secondary causes: review diuretics, aspirin"],
        ],
        col_widths=[4*cm, 6.5*cm, 6.5*cm]
    )
    E += spacer(8)

    # ── 4. SPONDYLOARTHRITIS ─────────────────────────────────────────────────
    E += section_header("4. Spondyloarthritis (SpA)", "HLA-B27 Associated Seronegative Arthritides")
    E += key_box([
        "Group of related syndromes: ankylosing spondylitis, psoriatic arthritis, reactive arthritis, enteropathic arthritis.",
        "HLA-B27 positive in ~90% of ankylosing spondylitis patients.",
        "RF negative (seronegative); enthesitis is the pathologic hallmark.",
        "Classified as axial SpA (spine/sacroiliac predominant) or peripheral SpA.",
    ])

    E += h2("Common Features Across All SpA Subtypes")
    E += make_table(
        ["Feature", "Description"],
        [
            ["Enthesitis", "Inflammation at tendon/ligament insertions (e.g., Achilles, plantar fascia, iliac crest) — HALLMARK of SpA"],
            ["Sacroiliitis", "Inflammation of sacroiliac joints; key diagnostic feature on imaging"],
            ["Asymmetric oligoarthritis", "Typically lower limb large joints (knee, ankle, hip)"],
            ["Dactylitis", "'Sausage digit' — diffuse swelling of an entire finger/toe; very specific for SpA"],
            ["Anterior uveitis", "Most common extra-articular feature across SpA subtypes"],
            ["HLA-B27", "Present in ~90% AS, ~75% reactive arthritis, ~50% psoriatic arthritis with axial disease"],
            ["RF negative", "Key feature distinguishing SpA from RA"],
        ],
        col_widths=[4*cm, 13*cm]
    )

    E += h2("Ankylosing Spondylitis (AS)")
    E += bullets([
        "Chronic inflammatory disease of spine and sacroiliac joints; predominantly young men <40 years",
        "<b>Inflammatory back pain:</b> insidious onset, worse at night and in the morning, <b>improved with exercise</b> (opposite of mechanical back pain), relieved poorly by rest",
        "Schober test: measures lumbar flexion limitation",
        "X-ray: sacroiliitis → 'bamboo spine' (syndesmophytes, spinal fusion) in late disease",
        "MRI: detects active sacroiliitis before X-ray changes (bone marrow oedema)",
        "Extra-articular: anterior uveitis, aortitis, aortic regurgitation, apical pulmonary fibrosis, cauda equina syndrome",
        "<b>Treatment:</b> NSAIDs (first-line) + physiotherapy (mandatory); anti-TNF biologics (adalimumab, etanercept) for refractory disease; IL-17 inhibitors (secukinumab, ixekizumab)",
    ])
    E += spacer(8)

    # ── 5. PSORIATIC ARTHRITIS ────────────────────────────────────────────────
    E += section_header("5. Psoriatic Arthritis (PsA)", "Seronegative SpA Associated with Psoriasis")
    E += key_box([
        "Affects 5–7% of psoriasis patients (up to 40% of hospitalised patients with extensive psoriasis).",
        "Psoriatic skin lesions precede arthritis in 70% of cases; family history is important when skin lesions absent.",
        "DIP joint involvement and enthesitis distinguish PsA from RA.",
        "RF usually negative.",
    ])
    E += h2("Clinical Patterns (5 Types)")
    E += make_table(
        ["Pattern", "Features", "Frequency"],
        [
            ["Oligoarticular asymmetric", "Asymmetric involvement of <5 joints; large joints; most common presentation", "~70% (classic)"],
            ["Symmetric polyarticular", "Resembles RA; multiple small joints; but DIP involved, RF negative", "~15%"],
            ["DIP-predominant", "Mainly DIP joints; associated with nail disease (pitting, onycholysis)", "~5%"],
            ["Spondylitic/axial", "Sacroiliitis ± spondylitis; may be asymptomatic radiographically", "~5%"],
            ["Arthritis mutilans", "Most destructive; osteolysis of phalanges/metacarpals → 'telescoping fingers' (opera glass hand)", "~5%"],
        ],
        col_widths=[4*cm, 9*cm, 4*cm]
    )
    E += h2("Diagnosis & Treatment")
    E += bullets([
        "X-ray: marginal erosions at DIP/PIP with periostitis (new bone formation); 'pencil-in-cup' deformity in arthritis mutilans",
        "CASPAR criteria used for diagnosis (psoriasis + arthritis + RF negative + imaging findings)",
        "<b>Treatment:</b> NSAIDs (1st line) → DMARDs (methotrexate, sulfasalazine) → anti-TNF biologics for axial/refractory disease",
        "IL-17 inhibitors (secukinumab) and IL-12/23 inhibitors (ustekinumab) also approved",
        "Avoid corticosteroid injections through psoriatic skin (colonised with Staph/Strep)",
    ])
    E += spacer(8)

    # ── 6. REACTIVE ARTHRITIS ─────────────────────────────────────────────────
    E += section_header("6. Reactive Arthritis", "Post-infectious Sterile Arthritis (formerly Reiter's Syndrome)")
    E += key_box([
        "Sterile inflammatory arthritis triggered by a distant infection — usually urogenital or enteric.",
        "Classic triad: arthritis + urethritis + conjunctivitis ('can't see, can't pee, can't climb a tree').",
        "HLA-B27 positive in ~75%; strongly associated.",
        "Usually self-limited (3–12 months).",
    ])
    E += h2("Triggering Organisms")
    E += make_table(
        ["Route", "Organisms"],
        [
            ["Urogenital (STI)", "Chlamydia trachomatis (most common in developed countries)"],
            ["Enteric (food/waterborne)", "Salmonella, Shigella, Yersinia, Campylobacter, Clostridioides difficile"],
        ],
        col_widths=[4*cm, 13*cm]
    )
    E += h2("Clinical Features & Treatment")
    E += bullets([
        "Asymmetric oligoarthritis of lower limbs (knees, ankles, feet) 1–4 weeks after infection",
        "Enthesitis (Achilles, plantar fascia), dactylitis",
        "Mucocutaneous: oral ulcers (painless), keratoderma blennorrhagica (psoriasiform skin lesions on palms/soles), circinate balanitis",
        "Ocular: conjunctivitis (mild, bilateral) or anterior uveitis",
        "<b>Treatment:</b> NSAIDs for arthritis; antibiotics for active infection (Chlamydia: doxycycline/azithromycin); DMARDs (sulfasalazine, methotrexate) for chronic/recurrent disease",
    ])
    E += spacer(8)

    # ── 7. SEPTIC ARTHRITIS ───────────────────────────────────────────────────
    E += section_header("7. Septic (Infectious) Arthritis", "Orthopedic Emergency — Prompt Diagnosis Required")
    E += key_box([
        "Orthopedic emergency: loss of joint function in 25–50% of patients even with prompt treatment.",
        "Most common organism: Staphylococcus aureus (all ages).",
        "Incidence: 2–10/100,000 in native joints; jumps to 30–70/100,000 in RA patients.",
        "Joint aspiration is mandatory for diagnosis — do not delay pending imaging.",
    ])
    E += h2("Pathways & Organisms")
    E += make_table(
        ["Mechanism", "Details"],
        [
            ["Hematogenous (most common)", "Bacteraemia seeds synovial membrane; explains why septic arthritis may coexist with osteomyelitis"],
            ["Direct inoculation", "Trauma, joint aspiration, or injection"],
            ["Contiguous spread", "Adjacent osteomyelitis, soft tissue infection"],
        ],
        col_widths=[4.5*cm, 12.5*cm]
    )
    E += make_table(
        ["Population", "Common Organisms"],
        [
            ["All adults", "S. aureus (most common), Streptococcus spp."],
            ["Sexually active young adults", "Neisseria gonorrhoeae (most common cause of septic arthritis in <40 y adults)"],
            ["IV drug users, immunocompromised", "S. aureus (including MRSA), Gram-negative bacilli (Pseudomonas)"],
            ["Neonates/infants", "S. aureus, Group B Streptococcus, Gram-negative rods"],
            ["Prosthetic joint (early <3 months)", "S. aureus, coagulase-negative staph, Gram-negatives"],
        ],
        col_widths=[5*cm, 12*cm]
    )

    E += h2("Clinical Features")
    E += bullets([
        "Acute onset severe monoarticular pain; exacerbated by any range of motion",
        "Cardinal signs: swelling, erythema, warmth; joint held in position of slight flexion (greatest comfort)",
        "Fever >80% of children; only ~40% of adults (especially immunosuppressed/steroid users may have minimal fever)",
        "Adults: knee (50%), hip (25%), shoulder (15%)",
        "Gonococcal septic arthritis: may present with migratory polyarthralgia → monoarthritis + skin vesiculopustular lesions + tenosynovitis",
    ])

    E += h2("Diagnosis")
    E += make_table(
        ["Investigation", "Expected Findings"],
        [
            ["Joint aspiration (mandatory)", "Turbid fluid; WBC >50,000/mm³ (often >100,000), >90% neutrophils; Gram stain and culture"],
            ["Blood cultures", "Often positive in hematogenous septic arthritis (draw before antibiotics)"],
            ["Serum WBC, CRP, ESR", "Elevated but non-specific"],
            ["X-ray", "Initially normal; useful to exclude fracture; late: joint space loss, osteomyelitis"],
            ["MRI", "Best for hip septic arthritis; detects osteomyelitis, soft tissue extension"],
            ["Ultrasound", "Detects joint effusion; guides aspiration (especially hip)"],
        ],
        col_widths=[4.5*cm, 12.5*cm]
    )

    E += h2("Treatment")
    E += bullets([
        "<b>IV antibiotics empirically:</b> anti-staphylococcal (flucloxacillin or vancomycin for MRSA risk); adjust to culture/sensitivity",
        "<b>Duration:</b> typically 2–4 weeks IV → oral switch; total 4–6 weeks for S. aureus",
        "<b>Surgical drainage:</b> hip joint always requires surgical drainage (arthroscopy or open); knee can often be managed with repeated aspiration",
        "Gonococcal arthritis: IV ceftriaxone → oral switch; excellent prognosis",
        "Physiotherapy: early passive range of motion once infection controlled to prevent ankylosis",
    ])
    E.append(PageBreak())

    # ── COMPARISON TABLES ─────────────────────────────────────────────────────
    E += section_header("Summary & Comparison Tables", "Quick Reference for Diagnosis and Differentiation")
    E += spacer(6)

    E += h2("Table 1: Diagnostic Comparison — All 7 Types")
    E += make_table(
        ["Type", "Age/Sex", "Joints Affected", "Key Lab/Imaging", "Hallmark Feature"],
        [
            ["Osteoarthritis", "Elderly; F>M after 55", "Knees, hips, lumbar spine, DIP/PIP", "X-ray: osteophytes, JSN; Serology negative", "No systemic features; Heberden/Bouchard nodes; morning stiffness <30 min"],
            ["Rheumatoid Arthritis", "20–50 y; F>>M (3:1)", "MCP, PIP, wrists (symmetric); spares DIP", "RF+, Anti-CCP+, ↑ESR/CRP; X-ray erosions", "Symmetric synovitis; morning stiffness >1 hr; systemic features; extra-articular manifestations"],
            ["Gout", "Men 40–60; postmeno women", "1st MTP (podagra), ankles, knees", "↑Uric acid; −ve birefringent crystals in fluid", "Acute severe monoarthritis; nocturnal onset; podagra; tophi"],
            ["Ankylosing Spondylitis", "Young men <40", "Sacroiliac joints, spine", "HLA-B27+; MRI sacroiliitis; bamboo spine on X-ray", "Inflammatory back pain improved with exercise; enthesitis; iritis"],
            ["Psoriatic Arthritis", "Any; psoriasis history", "DIP joints, large joints, axial; asymmetric", "HLA+(multiple); pencil-in-cup deformity; RF neg", "Nail changes (pitting, onycholysis); DIP involvement; enthesitis; dactylitis"],
            ["Reactive Arthritis", "Young adults post-infection", "Lower limb large joints; asymmetric", "HLA-B27+; cultures of infection trigger", "Post-infectious; classic triad (urethritis, conjunctivitis, arthritis)"],
            ["Septic Arthritis", "Any (children, elderly, immunocomp)", "Knee > Hip > Shoulder; monoarticular", "Joint fluid WBC >50,000; Gram stain/culture +ve", "Orthopedic emergency; fever; acute severe monoarthritis"],
        ],
        col_widths=[3*cm, 3*cm, 4*cm, 4*cm, 4.5*cm]
    )

    E += h2("Table 2: OA vs. RA — Head-to-Head Comparison")
    E += make_table(
        ["Feature", "Osteoarthritis", "Rheumatoid Arthritis"],
        [
            ["Primary mechanism", "Mechanical injury to articular cartilage", "Autoimmunity (T-cell and antibody-mediated)"],
            ["Role of inflammation", "Secondary; exacerbates cartilage damage", "Primary — drives all joint destruction"],
            ["Joints involved", "Weight-bearing: knees, hips; DIP joints", "Small joints: MCPs, PIPs, wrists (symmetric); spares DIP"],
            ["Morning stiffness", "<30 minutes", ">1 hour"],
            ["Systemic involvement", "No", "Yes: lungs, heart, eyes, cervical spine, blood"],
            ["Serology", "RF, ANA negative", "RF+ in 80%; Anti-CCP+ in ~70% (95% specific)"],
            ["Pathology", "Cartilage degeneration, osteophytes, subchondral cysts", "Pannus formation, marginal erosions, ankylosis"],
            ["Synovial fluid", "Non-inflammatory (<2,000 WBC/mm³)", "Inflammatory (>2,000–50,000+ WBC/mm³)"],
            ["Treatment", "NSAIDs, physiotherapy, joint replacement", "DMARDs (MTX), biologics (anti-TNF, IL-6i, JAKi)"],
        ],
        col_widths=[4.5*cm, 6*cm, 6*cm]
    )

    E += h2("Table 3: Synovial Fluid Analysis in Arthritis")
    E += make_table(
        ["Category", "WBC/mm³", "Appearance", "Conditions"],
        [
            ["Normal", "<200", "Clear, viscous", "Normal joint"],
            ["Non-inflammatory", "200–2,000", "Clear/yellow, viscous", "OA, trauma, early SLE"],
            ["Inflammatory", "2,000–50,000", "Turbid, yellow, low viscosity", "RA, gout, pseudogout, SpA, reactive arthritis"],
            ["Septic (presumed)", ">50,000 (often >100,000)", "Turbid/purulent, very low viscosity", "Bacterial septic arthritis"],
            ["Haemorrhagic", "Variable (RBCs)", "Red/bloody", "Trauma, haemophilia, pigmented villonodular synovitis"],
        ],
        col_widths=[3.5*cm, 3.5*cm, 5*cm, 5.5*cm]
    )

    E += h2("Table 4: Crystal Arthropathies Comparison")
    E += make_table(
        ["Feature", "Gout (MSU)", "Pseudogout (CPPD)"],
        [
            ["Crystal type", "Monosodium urate (MSU)", "Calcium pyrophosphate dihydrate (CPPD)"],
            ["Birefringence", "Negatively birefringent; needle-shaped", "Weakly positively birefringent; rhomboid-shaped"],
            ["Common joints", "1st MTP (podagra), ankles, knees", "Knees (most common), wrists, hips"],
            ["Age/sex", "Middle-aged men; postmeno women", "Elderly; equal sex distribution"],
            ["X-ray", "Punched-out erosions; tophi calcifications", "Chondrocalcinosis (calcification in cartilage)"],
            ["Underlying causes", "Hyperuricemia; thiazides, renal failure", "Hyperparathyroidism, haemochromatosis, hypomagnesaemia"],
            ["Acute treatment", "NSAIDs, colchicine, corticosteroids", "NSAIDs, colchicine, corticosteroids"],
            ["Long-term treatment", "Allopurinol/febuxostat (urate-lowering)", "No specific crystal-reducing therapy available"],
        ],
        col_widths=[4*cm, 6*cm, 7*cm]
    )

    E += h2("Table 5: Key Drug Summary in Arthritis Management")
    E += make_table(
        ["Drug/Class", "Mechanism", "Used In", "Key Side Effects"],
        [
            ["NSAIDs", "COX-1/2 inhibition → ↓prostaglandins", "OA, RA, Gout (acute), SpA, PsA, Reactive arthritis", "GI ulcers, renal impairment, CV risk, fluid retention"],
            ["Colchicine", "Inhibits microtubule polymerisation → ↓neutrophil chemotaxis", "Gout (acute + prophylaxis), CPPD, pericarditis", "GI: diarrhoea, nausea; myopathy (high dose); drug interactions (CYP3A4)"],
            ["Allopurinol", "Xanthine oxidase inhibitor → ↓uric acid synthesis", "Gout prevention (ULT)", "Rash (SJS in HLA-B*58:01 carriers), hypersensitivity syndrome"],
            ["Methotrexate", "Folic acid antagonist → anti-inflammatory via adenosine pathway", "RA (1st-line DMARD), PsA, other inflammatory arthritis", "Hepatotoxicity, myelosuppression, mucositis, pneumonitis; folate supplementation required"],
            ["Anti-TNF biologics", "Block TNF-α (key pro-inflammatory cytokine)", "RA, AS, PsA, IBD-related arthritis", "Infection risk (TB reactivation — screen with IGRA before use), injection site reactions"],
            ["IL-6 inhibitors (tocilizumab)", "Block IL-6 receptor", "RA (especially with systemic features)", "Infection, dyslipidaemia, liver enzyme elevation; may mask fever"],
            ["JAK inhibitors (tofacitinib)", "Inhibit JAK1/3 → ↓cytokine signalling", "RA, PsA, AS", "Infection, VTE risk, CV events; avoid in high CV risk patients"],
            ["Corticosteroids", "Broad anti-inflammatory via glucocorticoid receptor", "Bridging in RA, acute gout, septic arthritis (adjunct in some cases)", "Osteoporosis, hyperglycaemia, adrenal suppression, Cushing's features with prolonged use"],
        ],
        col_widths=[3.5*cm, 4*cm, 4*cm, 5.5*cm]
    )
    E += spacer(8)

    # Sources
    sources = [
        "Robbins & Kumar Basic Pathology, p. 790 — OA pathogenesis and OA vs RA comparison",
        "Textbook of Family Medicine 9e, pp. 873–893 — OA, RA, Gout, PsA, Reactive Arthritis",
        "Goldman-Cecil Medicine (International Edition) — Spondyloarthritis (Chapter 244)",
        "Rosen's Emergency Medicine — Septic Arthritis (p. 2730)",
        "Firestein & Kelley's Textbook of Rheumatology (2-Volume Set) — OA genetics, SpA",
    ]
    E += h2("Sources")
    E += bullets(sources)

    return E

# ── Build PDF ─────────────────────────────────────────────────────────────────
doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    leftMargin=MARGIN,
    rightMargin=MARGIN,
    topMargin=MARGIN + 0.7*cm,
    bottomMargin=MARGIN + 1.0*cm,
    title="Arthritis — Clinical Overview",
    author="Orris Medical AI",
    subject="All types of arthritis: pathology, diagnosis, treatment",
)

story = build_content()
doc.build(story, onFirstPage=on_page, onLaterPages=on_page)
print(f"PDF created: {OUTPUT}")

cd /home/daytona/workspace/arthritis-pdf && python3 generate_arthritis_pdf.py 2>…

ls -lh /home/daytona/workspace/arthritis-pdf/Arthritis_Clinical_Overview.pdf

ls -lh /home/daytona/workspace/arthritis-pdf/ && echo "---" && python3 -c " with…

python3 -c " import base64 with open('/home/daytona/workspace/arthritis-pdf/Arth…