A 30 year old female with history of recurrent sinusitis with elevated igE levels . CT showing b/l turbinate hypertrophy. Give me the correct harrison based approach , investigations and appropriate treatment , MD Medicine Style

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"chronic rhinosinusitis" AND "allergic rhinitis" AND management

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"chronic rhinosinusitis" AND treatment

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I now have comprehensive data from Goldman-Cecil Medicine and Cummings Otolaryngology. Let me compile the complete MD Medicine-style answer.

Recurrent Sinusitis with Elevated IgE + Bilateral Turbinate Hypertrophy - Harrison/MD Medicine Approach

Clinical Framework: What's Actually Going On

This 30-year-old female has a classic presentation of Chronic Rhinosinusitis (CRS) on an Allergic Background - specifically, what Goldman-Cecil classifies as hyperplastic eosinophilic CRS, the subset driven by Type 2 (TH2-mediated) inflammation. The elevated IgE is the key distinguishing marker. The bilateral turbinate hypertrophy on CT is the structural consequence of chronic mucosal inflammation.

The unified airway concept applies here: allergic rhinitis and recurrent sinusitis share common TH2 pathophysiology. ~80% of patients with allergic asthma also have allergic rhinitis; screen for lower airway involvement.

Step 1: Diagnosis Refinement - Is This Allergic CRS?

Diagnostic Criteria for CRS (EPOS/Goldman-Cecil, Table 394-5)

Symptoms persisting >3 months with TWO or more of:

Mucopurulent nasal drainage (anterior or posterior)
Nasal obstruction/congestion
Facial pressure/fullness
Reduced sense of smell (hyposmia/anosmia)

PLUS at least one objective finding:

Nasal/middle meatus polyps on endoscopy
Edema or purulence in middle meatus
Paranasal sinus opacification on CT

This patient satisfies both clinical and radiologic criteria.

Differentials to Exclude First (Goldman-Cecil Table 394-3)

Category	Examples
Allergic	Seasonal AR, Perennial AR
Inflammatory	NARES (non-allergic rhinitis with eosinophilia), CRS with/without polyps
Anatomic	Septal deviation, neoplasm
Hormonal	Hypothyroidism, OCP use
Vasculitic	Granulomatosis with Polyangiitis (Wegener's) - check for saddle nose, hemoptysis
Aspirin-exacerbated	Samter's triad (nasal polyps + asthma + ASA sensitivity)
Allergic fungal sinusitis	Elevated IgE + hyperdense sinus opacification on CT + specific IgE to fungi

Important: Elevated total IgE with specific unilateral expansion on CT should raise suspicion for Allergic Fungal Sinusitis (AFS) - characterized by elevated total IgE, specific IgE to colonizing fungi (Aspergillus, Alternaria), characteristic hyperdense mucin on CT, and eosinophilic mucin. This is a specific subtype requiring surgical management.

Step 2: Investigations (Systematic, MD Medicine Style)

A. Allergy Workup (Mandatory - Confirms Atopic Driver)

Skin Prick Testing (SPT) - First Line

Positive if wheal ≥3 mm larger than negative control
Sensitivity 80-100%, specificity 70-90% (Cummings ORL)
Stop antihistamines 2-7 days prior; stop omalizumab 8 weeks prior
Tests for: house dust mite, cockroach, moulds (Alternaria, Aspergillus, Cladosporium), pollens (trees, grasses, weeds), animal dander

Serum Specific IgE (ImmunoCAP/RAST)

Preferred if: severe dermatographism, active skin disease, inability to stop antihistamines, pregnancy
Total IgE > 100 IU/mL is strongly suggestive of atopic disease

Intradermal Testing

More sensitive than SPT; used to determine immunotherapy starting dilution (endpoint dilution method)
Reserved for when SPT is negative but clinical suspicion remains high

B. Nasal Assessment

Anterior Rhinoscopy / Nasal Endoscopy

Assess turbinate size, mucosal pallor/edema (bluish/pale mucosa = allergic)
Look for: nasal polyps (middle meatus), septal deviation, purulent discharge, allergic crease

Nasal Smear for Eosinophils

Distinguishes allergic rhinitis (eosinophils present) from NARES vs. vasomotor rhinitis

C. Imaging

CT Paranasal Sinuses (Non-contrast) - Already done

Bilateral turbinate hypertrophy confirmed
Assess: degree of ostiomeatal complex (OMC) obstruction, air-fluid levels, mucosal thickening, polyps, bony erosion
Lund-Mackay scoring for severity grading (each sinus 0-2; max 24)
Look for: hyperattenuating mucin within sinuses (AFS), bony expansion/erosion

Additional CT Finding Interpretation:

Mucosal thickening >3mm = significant
Complete opacification = advanced disease
Hyperdense material within sinus cavity = fungal mucin (suggestive of AFS)

D. Laboratory Investigations

Investigation	Rationale
CBC with differential	Eosinophilia (>500/µL supports atopic/eosinophilic CRS)
Total serum IgE	Quantify allergic burden; helps dose omalizumab if needed
ESR, CRP	Active infection vs. chronic inflammation
ANA, ANCA (c-ANCA/PR3)	Exclude GPA (Wegener's) if unusual features
Serum IgG, IgA, IgM	Exclude common variable immunodeficiency (CVID) in recurrent sinusitis
Sweat chloride / CFTR mutation	Exclude cystic fibrosis if bilateral bronchiectasis, recurrent pulmonary infections
Nasal NO (fractional)	Exclude primary ciliary dyskinesia
Aspergillus/Alternaria specific IgE	If AFS is suspected on CT
Beta-2 transferrin (nasal fluid)	Exclude CSF leak if clear, unilateral discharge

E. Pulmonary Assessment

Spirometry with bronchodilator reversibility
Fractional exhaled nitric oxide (FeNO) if asthma suspected
(Remember: 80% of allergic asthma patients have co-existing allergic rhinitis)

Step 3: Treatment - Stepwise Approach

Pillar 1: Allergen Avoidance (Primary Prevention)

Per Goldman-Cecil (Prevention section):

House dust mite: Allergen-impermeable mattress/pillow covers; humidity <50%; hot water washing of bedding (>130°F); vacuum with HEPA filter
Moulds: Dehumidification; treat window/shower areas with dilute bleach; avoid indoor plants in bedroom
Cockroaches: Extermination, sealing food sources
Pet dander: Ideally rehome; HEPA air purifier; exclude from bedroom; regular bathing of pets
Pollen: Air conditioning (filtered), close windows during high pollen season

Pillar 2: Pharmacotherapy

Step 1 - Mild/Intermittent Disease

Second-generation Oral H1 Antihistamines (once-daily, non-sedating):

Cetirizine 10 mg OD
Levocetirizine 5 mg OD
Loratadine 10 mg OD
Desloratadine 5 mg OD
Fexofenadine 180 mg OD

Antihistamines are most effective for sneezing, rhinorrhea, and pruritus. Their benefit diminishes with continuous allergen exposure (perennial AR). Provide only 20-30% symptom reduction.

Intranasal Antihistamines (faster onset, also effective for non-allergic rhinitis):

Azelastine nasal spray
Olopatadine nasal spray

Step 2 - Moderate/Persistent Disease (First-line for this patient)

Intranasal Corticosteroids (INCSs) - GOLD STANDARD (Goldman-Cecil, Table 394-6):

Drug	Dose/actuation	Dosing
Mometasone furoate	50 µg	2 sprays/nostril OD
Fluticasone propionate	50 µg	2 sprays/nostril OD
Fluticasone furoate	27.5 µg	2 sprays/nostril OD
Budesonide	32 µg	2 sprays/nostril BD
Triamcinolone acetonide	55 µg	2 sprays/nostril OD
Ciclesonide	50 µg	2 sprays/nostril OD

Provide 50-90% symptom reduction vs. 20-30% for antihistamines
Treatment of choice for moderate-severe or perennial AR
Also address turbinate hypertrophy - INCSs directly reduce mucosal edema
If adding antihistamine to INCS, prefer intranasal antihistamine over oral

Leukotriene Receptor Antagonists (LTRAs):

Montelukast 10 mg OD - efficacy comparable to antihistamines; useful add-on
Zileuton 1200 mg BD; Zafirlukast 20 mg BD (alternatives)
Particularly useful in Samter's triad (ASA-exacerbated disease)

Nasal Saline Irrigation:

Isotonic or hypertonic saline BD-TDS
Mechanical clearance of allergens and mucus; enhances ciliary function
Evidence-based adjunct in both AR and CRS

Oral Decongestants (short-term only):

Pseudoephedrine 30-60 mg q4-6h (max 240 mg/day)
Use for acute flares; risk of rebound congestion with prolonged use

Nasal Cromolyn:

Mast cell stabilizer; less effective than INCS
Useful preventively (pre-exposure to triggers), especially in mild-moderate disease
Requires QID dosing; less practical

Step 3 - Severe/Refractory Disease

Short Course Oral Corticosteroids:

Methylprednisolone taper (e.g., 8mg QID x1d → 4mg QID x2d → taper over 6 days)
Reserved for severe exacerbations; acute control before surgery

Ipratropium Bromide 0.03-0.06% (2 sprays per nostril q12h):

For rhinorrhea-predominant symptoms; useful in infectious rhinitis component

Antibiotics (for infectious exacerbations of CRS):

Acute bacterial rhinosinusitis (persisting >7-10 days without improvement):

First line: Amoxicillin 500 mg TDS OR Amoxicillin-clavulanate 875/125 mg BD x 7 days
Severe (fever >39°C, immunocompromised, recent abx use): Amoxicillin-clavulanate 2000/125 mg BD
Penicillin allergy: Doxycycline 100 mg BD OR Levofloxacin 500 mg OD OR Moxifloxacin 400 mg OD
Avoid: macrolides, 2nd/3rd generation cephalosporins (high resistance rates)
Note: Watchful waiting acceptable for 7-10 days first; 85% resolve without antibiotics

For chronic sinusitis - antibiotics are NOT the mainstay; cultures guide therapy if needed (direct sinus aspiration or endoscopy-guided middle meatus swab).

Pillar 3: Immunotherapy (Definitive/Disease-Modifying Therapy)

Subcutaneous Immunotherapy (SCIT) - Allergen Immunotherapy

Indicated: Failed adequate pharmacotherapy OR desire for durable benefit
Duration: 3-5 years total (build-up phase: weekly injections escalating over months; maintenance: monthly)
Evidence: Multiple systematic reviews demonstrate significant reduction in rhinitis/rhinoconjunctivitis symptoms, QOL improvement, reduced medication use (Cummings ORL)
Also prevents new sensitizations and reduces risk of asthma development
Contraindications: Poorly controlled asthma, active autoimmune disease, malignancy, pregnancy (initiation), beta-blocker use (relative)
Observe for 30 minutes post-injection (risk of anaphylaxis, rate 0.1%; fatalities extremely rare)

Sublingual Immunotherapy (SLIT)

FDA-approved for grass and house dust mite (tablets)
Better safety profile than SCIT; growing acceptance
Options: Grass pollen tablets, HDM tablets (Odactra/Acarizax)

Pillar 4: Biologics (For Refractory CRS with Nasal Polyps / Type 2 Inflammation)

If CRS with nasal polyps (CRSwNP) is confirmed and refractory to above:

Biologic	Dose	Target	Approval
Dupilumab	300 mg SC q2 weeks	IL-4Rα (IL-4 + IL-13)	CRSwNP
Omalizumab	SC (dose by weight + IgE)	IgE	CRSwNP
Mepolizumab	100 mg SC q4 weeks	IL-5	CRSwNP

Reserve for: recurrent disease post-FESS, or comorbidities precluding surgery
Tezepelumab (anti-TSLP, NEJM 2025 Phase III RCT - PMID 40106374) is emerging as another option

Recent evidence (Cai S et al., Allergy 2025, PMID 39985317 - meta-analysis): Biologics demonstrate superior efficacy and safety in CRSwNP in real-world settings.

Pillar 5: Surgical Options

For Turbinate Hypertrophy (if medical therapy fails):

Per Cummings Otolaryngology:

Mucosal redundancy or bony turbinate hypertrophy will NOT respond to medical therapy - these patients are surgical candidates
Do NOT perform total turbinectomy - risks "empty nose syndrome" (atrophic rhinitis, paradoxical obstruction, chronic dryness/crusting)

Surgical Options for Inferior Turbinate Hypertrophy:

Partial inferior turbinectomy (submucous resection)
Turbinoplasty (modified Mabry technique - preferred; preserves mucociliary function)
Radiofrequency volume reduction (RFVTR/Coblation) - minimally invasive, good functional preservation
Laser-assisted turbinoplasty (Holmium:YAG or KTP)
Microdebrider-assisted turbinoplasty
Cryosurgery
Infrared coagulation / electrical coagulation

Key surgical principle: Preserve enough turbinate tissue to maintain mucociliary clearance and prevent empty nose syndrome.

For Chronic Rhinosinusitis (if medical therapy fails - 3+ months of maximal therapy):

Functional Endoscopic Sinus Surgery (FESS)

Opens OMC; removes obstructing tissue; improves mucociliary drainage
Performed endoscopically (endonasal, no skin incisions)
Evidence: Benefits patients with recurrent acute sinusitis and CRS refractory to medical treatment
Post-operative saline irrigations + INCS maintenance essential
Note: Even with aggressive therapy, patients with severe Type 2 eosinophilic inflammation may have early recurrence with nasal polyps

When to Refer to ENT (Goldman-Cecil Table 394-7)

Temperature >39°C with orbital edema, severe headache, visual disturbance, altered mental status, meningeal signs (complications of acute sinusitis - emergency)
Failure to respond to >2 courses of antimicrobial therapy
Anatomic abnormalities, nosocomial infection
Immunocompromised or multiple comorbidities
Unusual/resistant pathogens
Fungal sinusitis or granulomatous disease
Recurrent episodes suggesting chronic sinusitis (this patient)

Summary Management Algorithm for this Patient

STEP 1: Confirm CRS + Allergic Background
  → Nasal endoscopy + allergy testing (SPT/serum IgE)
  → CBC, IgG/IgA/IgM, ANCA (exclude GPA/CVID)
  → Spirometry (co-existing asthma screen)

STEP 2: Allergen Avoidance + Education

STEP 3: Pharmacotherapy
  → INCS (mometasone/fluticasone) + nasal saline irrigation (daily)
  → Add: montelukast 10mg OD + 2nd gen antihistamine PRN
  → Antibiotic course only during acute bacterial exacerbations

STEP 4: Persist 3 months → reassess
  If adequate control → continue + consider SLIT/SCIT

STEP 5: If inadequate control → ENT referral
  → Nasal endoscopy + CT review (Lund-Mackay)
  → Consider: FESS + turbinate reduction
  → Post-surgical INCS maintenance

STEP 6: CRSwNP/Type 2 refractory disease
  → Dupilumab / Omalizumab / Mepolizumab

Sources:

Goldman-Cecil Medicine (International Edition), Chapter 394 (Rhinitis, Sinusitis, Rhinosinusitis) - Primary reference
Cummings Otolaryngology Head & Neck Surgery, Chapters 35, 29
Scott-Brown's Otorhinolaryngology, Vol. 1 & 2
Recent: Cai S et al. Allergy 2025 [PMID 39985317] - Biologics meta-analysis; Lipworth BJ et al. NEJM 2025 [PMID 40106374] - Tezepelumab RCT in CRSwNP

Create a management flowchart/PDF for this case

Reading File

Running Command

mkdir -p /home/daytona/workspace/sinusitis-flowchart && ls /home/daytona/workspace/sinusitis-flowchart

Writing File

~/sinusitis-flowchart/generate_flowchart.py

"""
Management Flowchart PDF for:
Recurrent Sinusitis + Elevated IgE + Bilateral Turbinate Hypertrophy
MD Medicine Style (Harrison/Goldman-Cecil based)
"""

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.units import mm, cm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    HRFlowable, KeepTogether
)
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY
from reportlab.platypus.flowables import Flowable
import reportlab.lib.colors as rcolors

# ─── Color Palette ────────────────────────────────────────────────────────────
NAVY       = colors.HexColor("#1B3A6B")
STEEL      = colors.HexColor("#2E6DA4")
TEAL       = colors.HexColor("#1A7A7A")
AMBER      = colors.HexColor("#D4850A")
RED_DARK   = colors.HexColor("#B03030")
GREEN_DARK = colors.HexColor("#2A7A2A")
PURPLE     = colors.HexColor("#5B3A8C")
LIGHT_BLUE = colors.HexColor("#D6E8F7")
LIGHT_TEAL = colors.HexColor("#D0EFEF")
LIGHT_AMBER= colors.HexColor("#FEF3DC")
LIGHT_RED  = colors.HexColor("#FAE0E0")
LIGHT_GREEN= colors.HexColor("#DCF0DC")
LIGHT_PURP = colors.HexColor("#EDE5F5")
LIGHT_GREY = colors.HexColor("#F4F4F4")
MID_GREY   = colors.HexColor("#CCCCCC")
WHITE      = colors.white
BLACK      = colors.black

W, H = A4  # 595.27 x 841.89

# ─── Document Setup ───────────────────────────────────────────────────────────
doc = SimpleDocTemplate(
    "/home/daytona/workspace/sinusitis-flowchart/Sinusitis_Management_Flowchart.pdf",
    pagesize=A4,
    leftMargin=15*mm, rightMargin=15*mm,
    topMargin=12*mm,  bottomMargin=12*mm,
    title="Sinusitis Management Flowchart",
    author="Orris MD Medicine Reference"
)

styles = getSampleStyleSheet()

# Custom styles
def S(name, **kw):
    return ParagraphStyle(name, **kw)

title_style = S("Title2",
    fontName="Helvetica-Bold", fontSize=15, textColor=WHITE,
    alignment=TA_CENTER, spaceAfter=2, leading=18)

subtitle_style = S("Subtitle2",
    fontName="Helvetica", fontSize=9, textColor=WHITE,
    alignment=TA_CENTER, spaceAfter=0, leading=12)

section_hdr = S("SectionHdr",
    fontName="Helvetica-Bold", fontSize=9.5, textColor=WHITE,
    alignment=TA_CENTER, leading=12, spaceAfter=0)

body_bold = S("BodyBold",
    fontName="Helvetica-Bold", fontSize=8, textColor=BLACK,
    leading=10, spaceAfter=1)

body_small = S("BodySmall",
    fontName="Helvetica", fontSize=7.5, textColor=BLACK,
    leading=9.5, spaceAfter=1)

body_tiny = S("BodyTiny",
    fontName="Helvetica", fontSize=7, textColor=BLACK,
    leading=9, spaceAfter=0)

drug_style = S("Drug",
    fontName="Helvetica-Oblique", fontSize=7.5, textColor=colors.HexColor("#1B3A6B"),
    leading=9.5)

warn_style = S("Warn",
    fontName="Helvetica-BoldOblique", fontSize=7.5, textColor=RED_DARK,
    leading=9.5)

note_style = S("Note",
    fontName="Helvetica-Oblique", fontSize=7, textColor=colors.HexColor("#444444"),
    leading=9)

# ─── Helper: make a colored header cell ───────────────────────────────────────
def hdr_cell(text, bg=NAVY, fg=WHITE, size=9.5, bold=True):
    fn = "Helvetica-Bold" if bold else "Helvetica"
    st = S(f"hdr_{text[:8]}", fontName=fn, fontSize=size,
           textColor=fg, alignment=TA_CENTER, leading=12)
    return Paragraph(text, st)

def body_cell(text, bold=False, color=BLACK, size=7.5, align=TA_LEFT):
    fn = "Helvetica-Bold" if bold else "Helvetica"
    st = S(f"bc_{text[:8]}", fontName=fn, fontSize=size,
           textColor=color, alignment=align, leading=9.5)
    return Paragraph(text, st)

def bullet(items, color=BLACK, size=7.5):
    lines = []
    for item in items:
        lines.append(Paragraph(f"• {item}", S("blt",
            fontName="Helvetica", fontSize=size, textColor=color,
            leading=9.5, leftIndent=6)))
    return lines

# ─── Arrow Flowable ───────────────────────────────────────────────────────────
class Arrow(Flowable):
    def __init__(self, width=40, height=14, color=STEEL, label=""):
        super().__init__()
        self.width = width
        self.height = height
        self._color = color
        self.label = label

    def draw(self):
        c = self.canv
        w, h = self.width, self.height
        c.setFillColor(self._color)
        c.setStrokeColor(self._color)
        shaft_w = w * 0.55
        shaft_h = h * 0.38
        tip_w = w * 0.45
        cx = w / 2
        # shaft
        c.rect(cx - shaft_w/2, h*0.38, shaft_w, shaft_h, fill=1, stroke=0)
        # arrowhead
        path = c.beginPath()
        path.moveTo(cx, 0)
        path.lineTo(cx - tip_w/2, h*0.42)
        path.lineTo(cx + tip_w/2, h*0.42)
        path.close()
        c.drawPath(path, fill=1, stroke=0)
        if self.label:
            c.setFont("Helvetica-Bold", 7)
            c.setFillColor(WHITE)
            c.drawCentredString(cx, h*0.52, self.label)

    def wrap(self, *args):
        return self.width, self.height

class CentredArrow(Flowable):
    """Arrow centred in available width"""
    def __init__(self, avail_width, color=STEEL, label=""):
        super().__init__()
        self._avail = avail_width
        self._color = color
        self.label = label
        self.height = 14

    def draw(self):
        c = self.canv
        w, h = 50, self.height
        ox = (self._avail - w) / 2
        c.saveState()
        c.translate(ox, 0)
        shaft_w = w * 0.5
        shaft_h = h * 0.38
        tip_w = w * 0.4
        cx = w / 2
        c.setFillColor(self._color)
        c.setStrokeColor(self._color)
        c.rect(cx - shaft_w/2, h*0.38, shaft_w, shaft_h, fill=1, stroke=0)
        path = c.beginPath()
        path.moveTo(cx, 0)
        path.lineTo(cx - tip_w/2, h*0.42)
        path.lineTo(cx + tip_w/2, h*0.42)
        path.close()
        c.drawPath(path, fill=1, stroke=0)
        if self.label:
            c.setFont("Helvetica-Bold", 7)
            c.setFillColor(WHITE)
            c.drawCentredString(cx, h*0.52, self.label)
        c.restoreState()

    def wrap(self, avail_w, avail_h):
        self._avail = avail_w
        return avail_w, self.height

# ─── Build Content ────────────────────────────────────────────────────────────
story = []
FULL_W = W - 30*mm  # 165mm usable

# ══════════════════════════════════════════════════════════════════════════════
# TITLE BANNER
# ══════════════════════════════════════════════════════════════════════════════
title_data = [[
    hdr_cell("MANAGEMENT FLOWCHART", bg=NAVY, fg=WHITE, size=14),
    hdr_cell("Recurrent Sinusitis + Elevated IgE + Bilateral Turbinate Hypertrophy", bg=NAVY, fg=colors.HexColor("#AADDFF"), size=9, bold=False),
]]
title_tbl = Table(title_data, colWidths=[FULL_W * 0.38, FULL_W * 0.62])
title_tbl.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), NAVY),
    ("ALIGN", (0,0), (-1,-1), "CENTER"),
    ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
    ("TOPPADDING", (0,0), (-1,-1), 8),
    ("BOTTOMPADDING", (0,0), (-1,-1), 8),
    ("LEFTPADDING", (0,0), (-1,-1), 6),
    ("RIGHTPADDING", (0,0), (-1,-1), 6),
    ("ROUNDEDCORNERS", [4,4,4,4]),
]))
story.append(title_tbl)

# Subtitle bar
sub_data = [[
    hdr_cell("Female, 30 yrs  |  Hx: Recurrent Sinusitis  |  ↑ Total IgE  |  CT: B/L Turbinate Hypertrophy",
             bg=STEEL, fg=WHITE, size=8.5, bold=False)
]]
sub_tbl = Table(sub_data, colWidths=[FULL_W])
sub_tbl.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), STEEL),
    ("ALIGN", (0,0), (-1,-1), "CENTER"),
    ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
    ("TOPPADDING", (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
]))
story.append(sub_tbl)
story.append(Spacer(1, 4*mm))

# ══════════════════════════════════════════════════════════════════════════════
# STEP 1: INITIAL ASSESSMENT
# ══════════════════════════════════════════════════════════════════════════════
def make_step_header(text, bg=NAVY, width=FULL_W):
    d = [[hdr_cell(text, bg=bg, size=9)]]
    t = Table(d, colWidths=[width])
    t.setStyle(TableStyle([
        ("BACKGROUND",(0,0),(-1,-1), bg),
        ("ALIGN",(0,0),(-1,-1),"CENTER"),
        ("VALIGN",(0,0),(-1,-1),"MIDDLE"),
        ("TOPPADDING",(0,0),(-1,-1),5),
        ("BOTTOMPADDING",(0,0),(-1,-1),5),
        ("LEFTPADDING",(0,0),(-1,-1),6),
        ("RIGHTPADDING",(0,0),(-1,-1),6),
    ]))
    return t

# STEP 1
story.append(make_step_header("STEP 1 — CLINICAL DIAGNOSIS & DIFFERENTIAL", bg=NAVY))
story.append(Spacer(1, 1.5*mm))

diag_data = [
    [
        # Col 1: CRS Criteria
        [
            Paragraph("<b>CRS Diagnostic Criteria (EPOS/Goldman-Cecil)</b>", S("x", fontName="Helvetica-Bold", fontSize=8, textColor=NAVY, leading=10)),
            Paragraph("Symptoms >3 months (≥2 of):", body_small),
        ] + bullet([
            "Mucopurulent nasal drainage",
            "Nasal obstruction / congestion",
            "Facial pressure / fullness",
            "Hyposmia / anosmia",
        ], color=colors.HexColor("#1B3A6B")) + [
            Paragraph("<b>PLUS objective finding:</b>", S("x2", fontName="Helvetica-Bold", fontSize=7.5, textColor=NAVY, leading=9.5)),
        ] + bullet([
            "Nasal/middle meatus polyps",
            "Edema / purulence in middle meatus",
            "CT: sinus opacification",
        ], color=colors.HexColor("#1B3A6B")),

        # Col 2: Differentials
        [
            Paragraph("<b>Rule Out (Key Differentials)</b>", S("x3", fontName="Helvetica-Bold", fontSize=8, textColor=RED_DARK, leading=10)),
        ] + bullet([
            "GPA (Wegener's): ANCA, saddle nose, hemoptysis",
            "NARES: nasal eosinophils, skin-test negative",
            "Vasomotor rhinitis: no eosinophils, irritant-driven",
            "Allergic Fungal Sinusitis: ↑IgE + hyperdense CT mucin",
            "Samter's Triad: polyps + asthma + ASA sensitivity",
            "CVID: ↓IgG/IgA/IgM, recurrent infections",
            "CSF rhinorrhea: β2-transferrin test",
            "Hypothyroidism / OCP-related rhinitis",
        ], color=RED_DARK),
    ]
]

diag_tbl = Table(diag_data, colWidths=[FULL_W*0.47, FULL_W*0.53])
diag_tbl.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (0,0), LIGHT_BLUE),
    ("BACKGROUND", (1,0), (1,0), LIGHT_RED),
    ("VALIGN", (0,0), (-1,-1), "TOP"),
    ("TOPPADDING", (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING", (0,0), (-1,-1), 6),
    ("RIGHTPADDING", (0,0), (-1,-1), 5),
    ("BOX", (0,0), (-1,-1), 0.5, MID_GREY),
    ("INNERGRID", (0,0), (-1,-1), 0.5, MID_GREY),
]))
story.append(diag_tbl)
story.append(Spacer(1, 2*mm))
story.append(CentredArrow(FULL_W, color=STEEL))
story.append(Spacer(1, 1*mm))

# ══════════════════════════════════════════════════════════════════════════════
# STEP 2: INVESTIGATIONS
# ══════════════════════════════════════════════════════════════════════════════
story.append(make_step_header("STEP 2 — INVESTIGATIONS", bg=TEAL))
story.append(Spacer(1, 1.5*mm))

inv_data = [
    # Header row
    [
        hdr_cell("ALLERGY WORKUP", bg=TEAL, fg=WHITE, size=8),
        hdr_cell("NASAL / IMAGING", bg=TEAL, fg=WHITE, size=8),
        hdr_cell("LAB PANEL", bg=TEAL, fg=WHITE, size=8),
    ],
    [
        # Allergy
        [
            Paragraph("<b>Skin Prick Test (First Line)</b>", S("al1", fontName="Helvetica-Bold", fontSize=7.5, textColor=TEAL, leading=9.5)),
        ] + bullet([
            "HDM, cockroach, moulds",
            "Pollens, animal dander",
            "Positive: wheal ≥3mm > control",
            "Stop antihistamines 2–7 days prior",
            "Sensitivity 80–100%, Spec 70–90%",
        ], size=7) + [
            Paragraph("<b>Serum Specific IgE (ImmunoCAP)</b>", S("al2", fontName="Helvetica-Bold", fontSize=7.5, textColor=TEAL, leading=9.5)),
        ] + bullet([
            "If SPT contraindicated / skin disease",
            "Total IgE >100 IU/mL = strongly atopic",
            "Aspergillus/Alternaria IgE (if AFS suspected)",
        ], size=7),
        # Nasal/Imaging
        [
            Paragraph("<b>Nasal Endoscopy</b>", S("ni1", fontName="Helvetica-Bold", fontSize=7.5, textColor=TEAL, leading=9.5)),
        ] + bullet([
            "Turbinate size & mucosal colour",
            "Polyps (middle meatus)",
            "Purulent discharge",
            "Pale/bluish mucosa = allergic",
        ], size=7) + [
            Paragraph("<b>CT PNS (Non-contrast)</b>", S("ni2", fontName="Helvetica-Bold", fontSize=7.5, textColor=TEAL, leading=9.5)),
        ] + bullet([
            "Lund-Mackay score (max 24)",
            "OMC obstruction / polyps",
            "Hyperdense mucin → AFS",
            "Bony erosion → invasive fungal",
        ], size=7) + [
            Paragraph("<b>Nasal Smear</b>", S("ni3", fontName="Helvetica-Bold", fontSize=7.5, textColor=TEAL, leading=9.5)),
        ] + bullet([
            "Eosinophils = allergic / NARES",
            "Absent eos = vasomotor",
        ], size=7),
        # Labs
        [
            Paragraph("<b>Mandatory</b>", S("lb1", fontName="Helvetica-Bold", fontSize=7.5, textColor=TEAL, leading=9.5)),
        ] + bullet([
            "CBC + differential (eosinophilia?)",
            "Total serum IgE (quantify, dose biologic)",
            "ESR, CRP (inflammatory activity)",
        ], size=7) + [
            Paragraph("<b>If Clinically Indicated</b>", S("lb2", fontName="Helvetica-Bold", fontSize=7.5, textColor=TEAL, leading=9.5)),
        ] + bullet([
            "c-ANCA/p-ANCA, ANA → GPA",
            "IgG, IgA, IgM → exclude CVID",
            "Sweat chloride / CFTR → CF",
            "Nasal NO → primary ciliary dyskinesia",
            "β2-transferrin → CSF rhinorrhea",
            "Spirometry + FeNO → co-morbid asthma",
        ], size=7),
    ]
]

inv_tbl = Table(inv_data, colWidths=[FULL_W*0.33, FULL_W*0.35, FULL_W*0.32])
inv_tbl.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,0), TEAL),
    ("BACKGROUND", (0,1), (-1,1), LIGHT_TEAL),
    ("VALIGN", (0,0), (-1,-1), "TOP"),
    ("ALIGN", (0,0), (-1,0), "CENTER"),
    ("TOPPADDING", (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING", (0,0), (-1,-1), 5),
    ("RIGHTPADDING", (0,0), (-1,-1), 4),
    ("BOX", (0,0), (-1,-1), 0.5, MID_GREY),
    ("INNERGRID", (0,0), (-1,-1), 0.5, MID_GREY),
]))
story.append(inv_tbl)
story.append(Spacer(1, 2*mm))
story.append(CentredArrow(FULL_W, color=AMBER))
story.append(Spacer(1, 1*mm))

# ══════════════════════════════════════════════════════════════════════════════
# STEP 3: TREATMENT — ALLERGEN AVOIDANCE
# ══════════════════════════════════════════════════════════════════════════════
story.append(make_step_header("STEP 3 — TREATMENT: PILLAR 1 — ALLERGEN AVOIDANCE (Always First)", bg=AMBER))
story.append(Spacer(1, 1.5*mm))

avoid_data = [
    [
        [Paragraph("<b>HDM</b>", S("av1", fontName="Helvetica-Bold", fontSize=7.5, textColor=AMBER, leading=9))] +
        bullet(["Allergen-impermeable covers (mattress/pillow)", "Humidity <50%", "Hot water wash bedding >130°F", "HEPA vacuum"], size=7),
        [Paragraph("<b>Moulds</b>", S("av2", fontName="Helvetica-Bold", fontSize=7.5, textColor=AMBER, leading=9))] +
        bullet(["Dehumidify home", "Dilute bleach on windows/shower", "No indoor plants in bedroom"], size=7),
        [Paragraph("<b>Pollens</b>", S("av3", fontName="Helvetica-Bold", fontSize=7.5, textColor=AMBER, leading=9))] +
        bullet(["AC (filtered) in season", "Close windows during high pollen", "Shower after outdoor exposure"], size=7),
        [Paragraph("<b>Pets / Cockroaches</b>", S("av4", fontName="Helvetica-Bold", fontSize=7.5, textColor=AMBER, leading=9))] +
        bullet(["Rehome pet ideally; exclude from bedroom", "HEPA air purifier", "Exterminate cockroaches", "Seal food sources"], size=7),
    ]
]
avoid_tbl = Table(avoid_data, colWidths=[FULL_W*0.27, FULL_W*0.24, FULL_W*0.24, FULL_W*0.25])
avoid_tbl.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), LIGHT_AMBER),
    ("VALIGN", (0,0), (-1,-1), "TOP"),
    ("TOPPADDING", (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING", (0,0), (-1,-1), 5),
    ("RIGHTPADDING", (0,0), (-1,-1), 4),
    ("BOX", (0,0), (-1,-1), 0.5, MID_GREY),
    ("INNERGRID", (0,0), (-1,-1), 0.5, MID_GREY),
]))
story.append(avoid_tbl)
story.append(Spacer(1, 2*mm))
story.append(CentredArrow(FULL_W, color=AMBER))
story.append(Spacer(1, 1*mm))

# ══════════════════════════════════════════════════════════════════════════════
# STEP 4: PHARMACOTHERAPY (main table)
# ══════════════════════════════════════════════════════════════════════════════
story.append(make_step_header("STEP 4 — TREATMENT: PILLAR 2 — PHARMACOTHERAPY (Stepwise)", bg=STEEL))
story.append(Spacer(1, 1.5*mm))

pharm_hdr = [
    hdr_cell("STEP", bg=STEEL, size=8),
    hdr_cell("DISEASE SEVERITY", bg=STEEL, size=8),
    hdr_cell("DRUG CLASS", bg=STEEL, size=8),
    hdr_cell("AGENTS & DOSES", bg=STEEL, size=8),
    hdr_cell("NOTES", bg=STEEL, size=8),
]

def mk(t, bold=False, col=BLACK, size=7.5):
    return Paragraph(t, S("c", fontName="Helvetica-Bold" if bold else "Helvetica",
                           fontSize=size, textColor=col, leading=9.5))

pharm_rows = [
    pharm_hdr,
    [
        mk("1", bold=True, col=STEEL),
        mk("Mild / Intermittent"),
        mk("2nd-gen Antihistamines\n(oral)", bold=True),
        [
            mk("• Cetirizine 10 mg OD", size=7),
            mk("• Levocetirizine 5 mg OD", size=7),
            mk("• Loratadine 10 mg OD", size=7),
            mk("• Fexofenadine 180 mg OD", size=7),
            mk("• Desloratadine 5 mg OD", size=7),
        ],
        mk("Targets: sneezing, rhinorrhea, itch.\n20–30% symptom reduction.\nDiminished efficacy with continuous exposure.", size=7),
    ],
    [
        mk("", bold=True, col=STEEL),
        mk(""),
        mk("Intranasal Antihistamines", bold=True),
        [mk("• Azelastine nasal spray", size=7),
         mk("• Olopatadine nasal spray", size=7)],
        mk("Faster onset than oral. Also\neffective for non-allergic rhinitis.", size=7),
    ],
    [
        mk("2", bold=True, col=GREEN_DARK),
        mk("Moderate–Severe /\nPerennial (THIS PATIENT)", bold=True, col=GREEN_DARK),
        mk("Intranasal Corticosteroids\n★ GOLD STANDARD", bold=True, col=GREEN_DARK),
        [
            mk("• Mometasone furoate 50µg — 2 sprays/nostril OD", size=7),
            mk("• Fluticasone propionate 50µg — 2 sprays/nostril OD", size=7),
            mk("• Fluticasone furoate 27.5µg — 2 sprays/nostril OD", size=7),
            mk("• Budesonide 32µg — 2 sprays/nostril BD", size=7),
            mk("• Triamcinolone 55µg — 2 sprays/nostril OD", size=7),
        ],
        mk("50–90% symptom reduction.\nAlso reduces turbinate hypertrophy.\nPreferred for perennial AR.\nIf adding antihistamine to INCS,\nuse INTRANASAL antihistamine.", size=7, col=GREEN_DARK),
    ],
    [
        mk("", bold=True),
        mk("Add-on Therapy"),
        mk("Leukotriene Antagonists"),
        [mk("• Montelukast 10 mg OD (preferred)", size=7),
         mk("• Zileuton 1200 mg BD", size=7),
         mk("• Zafirlukast 20 mg BD", size=7)],
        mk("Comparable to antihistamines.\nKey role in Samter's triad.\nContinue with SPT (no interference).", size=7),
    ],
    [
        mk("", bold=True),
        mk("All stages — adjunct"),
        mk("Nasal Saline Irrigation"),
        [mk("• Isotonic or hypertonic saline", size=7),
         mk("• BD–TDS irrigation", size=7)],
        mk("Clears allergens & mucus.\nImproves ciliary function.\nEvidence-based in CRS.", size=7),
    ],
    [
        mk("", bold=True),
        mk("Acute congestion only"),
        mk("Oral Decongestants\n(short-term)"),
        [mk("• Pseudoephedrine 30–60 mg q4–6h", size=7),
         mk("  (max 240 mg/day)", size=7)],
        mk("Risk of rebound congestion.\nDo NOT use >3–5 days.", size=7, col=RED_DARK),
    ],
    [
        mk("3", bold=True, col=AMBER),
        mk("Severe exacerbation /\nPre-surgical"),
        mk("Oral Corticosteroids\n(short course)", bold=True),
        [mk("• Methylprednisolone 8mg QID×1d", size=7),
         mk("  → 4mg QID×2d → taper over 6d", size=7)],
        mk("Reserve for acute severe flares.\nBridge to surgery.", size=7, col=AMBER),
    ],
    [
        mk("", bold=True),
        mk("Acute bacterial\nexacerbation"),
        mk("Antibiotics\n(targeted use)", bold=True),
        [mk("1st line: Amoxicillin 500mg TDS", size=7),
         mk("         OR Amox-clav 875/125mg BD × 7d", size=7),
         mk("PCN allergy: Doxycycline 100mg BD", size=7),
         mk("            OR Levofloxacin 500mg OD", size=7),
         mk("Severe: Amox-clav 2000/125mg BD", size=7)],
        mk("Only if: symptoms >7–10d without improvement.\nWatchful waiting acceptable initially (85% resolve).\nAvoid macrolides / 2nd–3rd gen cephalosporins.", size=7),
    ],
]

pharm_tbl = Table(pharm_rows,
    colWidths=[FULL_W*0.05, FULL_W*0.14, FULL_W*0.17, FULL_W*0.38, FULL_W*0.26])

row_bgs = [STEEL, LIGHT_BLUE, LIGHT_BLUE, LIGHT_GREEN, LIGHT_BLUE, LIGHT_BLUE, LIGHT_AMBER, LIGHT_AMBER, LIGHT_RED]
ts = [
    ("BACKGROUND", (0,0), (-1,0), STEEL),
    ("VALIGN", (0,0), (-1,-1), "TOP"),
    ("ALIGN", (0,0), (0,-1), "CENTER"),
    ("TOPPADDING", (0,0), (-1,-1), 4),
    ("BOTTOMPADDING", (0,0), (-1,-1), 4),
    ("LEFTPADDING", (0,0), (-1,-1), 4),
    ("RIGHTPADDING", (0,0), (-1,-1), 4),
    ("BOX", (0,0), (-1,-1), 0.5, MID_GREY),
    ("INNERGRID", (0,0), (-1,-1), 0.5, MID_GREY),
    ("BACKGROUND", (0,1), (-1,1), LIGHT_BLUE),
    ("BACKGROUND", (0,2), (-1,2), LIGHT_BLUE),
    ("BACKGROUND", (0,3), (-1,3), LIGHT_GREEN),
    ("BACKGROUND", (0,4), (-1,4), LIGHT_BLUE),
    ("BACKGROUND", (0,5), (-1,5), LIGHT_BLUE),
    ("BACKGROUND", (0,6), (-1,6), LIGHT_AMBER),
    ("BACKGROUND", (0,7), (-1,7), LIGHT_AMBER),
    ("BACKGROUND", (0,8), (-1,8), LIGHT_RED),
    ("SPAN", (0,1), (0,2)),
    ("SPAN", (0,3), (0,5)),
    ("SPAN", (0,6), (0,7)),
]
pharm_tbl.setStyle(TableStyle(ts))
story.append(pharm_tbl)
story.append(Spacer(1, 2*mm))
story.append(CentredArrow(FULL_W, color=PURPLE))
story.append(Spacer(1, 1*mm))

# ══════════════════════════════════════════════════════════════════════════════
# STEP 5: IMMUNOTHERAPY
# ══════════════════════════════════════════════════════════════════════════════
story.append(make_step_header("STEP 5 — TREATMENT: PILLAR 3 — ALLERGEN IMMUNOTHERAPY (Disease-Modifying)", bg=PURPLE))
story.append(Spacer(1, 1.5*mm))

immuno_data = [
    [
        hdr_cell("SUBCUTANEOUS (SCIT)", bg=PURPLE, size=8),
        hdr_cell("SUBLINGUAL (SLIT)", bg=PURPLE, size=8),
        hdr_cell("INDICATIONS / CONTRA", bg=PURPLE, size=8),
    ],
    [
        [
            Paragraph("<b>Build-up phase:</b> Weekly injections, escalating over 3–6 months", S("i1", fontName="Helvetica", fontSize=7.5, textColor=BLACK, leading=9.5)),
        ] + bullet([
            "Maintenance: Monthly injections",
            "Total duration: 3–5 years",
            "Observe 30 min post-injection",
            "Systemic reaction rate: 0.1%",
            "Polysensitized: multi-allergen mix",
        ], size=7),
        [
            Paragraph("<b>FDA-approved tablets:</b>", S("i2", fontName="Helvetica", fontSize=7.5, textColor=BLACK, leading=9.5)),
        ] + bullet([
            "Grass pollen (Grastek)",
            "HDM (Odactra/Acarizax)",
            "Better safety profile than SCIT",
            "European first-choice for single allergen",
            "Daily sublingual dosing at home",
        ], size=7),
        [
            Paragraph("<b>Indications:</b>", S("i3", fontName="Helvetica-Bold", fontSize=7.5, textColor=GREEN_DARK, leading=9.5)),
        ] + bullet([
            "Failed pharmacotherapy",
            "Desire for durable benefit",
            "High-risk for developing asthma",
            "New sensitization prevention",
        ], size=7, color=GREEN_DARK) + [
            Paragraph("<b>Contraindications:</b>", S("i4", fontName="Helvetica-Bold", fontSize=7.5, textColor=RED_DARK, leading=9.5)),
        ] + bullet([
            "Poorly controlled asthma",
            "Active malignancy / autoimmune",
            "Initiating during pregnancy",
            "Beta-blockers (relative)",
        ], size=7, color=RED_DARK),
    ]
]
immuno_tbl = Table(immuno_data, colWidths=[FULL_W*0.35, FULL_W*0.32, FULL_W*0.33])
immuno_tbl.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,0), PURPLE),
    ("BACKGROUND", (0,1), (-1,1), LIGHT_PURP),
    ("VALIGN", (0,0), (-1,-1), "TOP"),
    ("TOPPADDING", (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING", (0,0), (-1,-1), 5),
    ("RIGHTPADDING", (0,0), (-1,-1), 5),
    ("BOX", (0,0), (-1,-1), 0.5, MID_GREY),
    ("INNERGRID", (0,0), (-1,-1), 0.5, MID_GREY),
]))
story.append(immuno_tbl)
story.append(Spacer(1, 2*mm))
story.append(CentredArrow(FULL_W, color=RED_DARK, label="Refractory?"))
story.append(Spacer(1, 1*mm))

# ══════════════════════════════════════════════════════════════════════════════
# STEP 6: SURGICAL + BIOLOGICS (side by side)
# ══════════════════════════════════════════════════════════════════════════════
story.append(make_step_header("STEP 6 — REFRACTORY DISEASE: SURGERY + BIOLOGICS", bg=RED_DARK))
story.append(Spacer(1, 1.5*mm))

surg_bio_data = [
    [
        hdr_cell("TURBINATE SURGERY\n(if medical therapy fails)", bg=colors.HexColor("#8B2020"), size=8),
        hdr_cell("FUNCTIONAL ENDOSCOPIC\nSINUS SURGERY (FESS)", bg=colors.HexColor("#8B2020"), size=8),
        hdr_cell("BIOLOGICS\n(CRSwNP + Type 2 Inflammation)", bg=colors.HexColor("#8B2020"), size=8),
    ],
    [
        [
            Paragraph("<b>⚠ Do NOT total turbinectomy</b> → Empty nose syndrome", S("s1", fontName="Helvetica-Bold", fontSize=7, textColor=RED_DARK, leading=9)),
            Paragraph("<b>Options (preserve mucociliary function):</b>", S("s2", fontName="Helvetica-Bold", fontSize=7.5, textColor=BLACK, leading=9.5)),
        ] + bullet([
            "Radiofrequency volume reduction (RFVTR)",
            "Turbinoplasty (modified Mabry technique)",
            "Microdebrider-assisted turbinoplasty",
            "Laser (Holmium:YAG / KTP)",
            "Partial inferior turbinectomy",
            "Cryosurgery / infrared coagulation",
        ], size=7),
        bullet([
            "Opens ostiomeatal complex (OMC)",
            "Removes obstructive tissue",
            "Improves mucus drainage",
            "Enhances future topical drug delivery",
            "Post-op: INCS + saline irrigation mandatory",
            "For recurrent acute + CRS refractory to 3+ months medical Rx",
        ], size=7) + [
            Paragraph("<b>Indication:</b> Failure after maximal\nmedical therapy (≥3 months)", S("s3", fontName="Helvetica-Bold", fontSize=7.5, textColor=RED_DARK, leading=9.5)),
        ],
        [
            Paragraph("<b>Agents (Goldman-Cecil):</b>", S("bio1", fontName="Helvetica-Bold", fontSize=7.5, textColor=BLACK, leading=9.5)),
        ] + [
            Paragraph("• <b>Dupilumab</b> 300mg SC q2wks (anti-IL-4Rα)", S("bio2", fontName="Helvetica", fontSize=7, textColor=BLACK, leading=9)),
            Paragraph("• <b>Omalizumab</b> SC (dose by weight + IgE) (anti-IgE)", S("bio3", fontName="Helvetica", fontSize=7, textColor=BLACK, leading=9)),
            Paragraph("• <b>Mepolizumab</b> 100mg SC q4wks (anti-IL-5)", S("bio4", fontName="Helvetica", fontSize=7, textColor=BLACK, leading=9)),
            Paragraph("• <b>Tezepelumab</b> (anti-TSLP) — Phase III 2025 [NEJM]", S("bio5", fontName="Helvetica", fontSize=7, textColor=BLACK, leading=9)),
            Spacer(1, 2),
            Paragraph("<b>Reserve for:</b>", S("bio6", fontName="Helvetica-Bold", fontSize=7.5, textColor=BLACK, leading=9.5)),
        ] + bullet([
            "Recurrent disease post-FESS",
            "Comorbidities precluding surgery",
            "Severe Type 2 eosinophilic CRS",
        ], size=7),
    ]
]
surg_bio_tbl = Table(surg_bio_data, colWidths=[FULL_W*0.31, FULL_W*0.34, FULL_W*0.35])
surg_bio_tbl.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,0), colors.HexColor("#8B2020")),
    ("BACKGROUND", (0,1), (-1,1), LIGHT_RED),
    ("VALIGN", (0,0), (-1,-1), "TOP"),
    ("TOPPADDING", (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING", (0,0), (-1,-1), 5),
    ("RIGHTPADDING", (0,0), (-1,-1), 5),
    ("BOX", (0,0), (-1,-1), 0.5, MID_GREY),
    ("INNERGRID", (0,0), (-1,-1), 0.5, MID_GREY),
]))
story.append(surg_bio_tbl)
story.append(Spacer(1, 2*mm))

# ══════════════════════════════════════════════════════════════════════════════
# WHEN TO REFER BOX
# ══════════════════════════════════════════════════════════════════════════════
refer_data = [
    [hdr_cell("⚠  WHEN TO REFER TO ENT IMMEDIATELY (Goldman-Cecil)", bg=colors.HexColor("#7B1515"), size=9)],
    [[
        Paragraph(
            "Temperature >39°C + orbital edema / severe headache / visual disturbance / altered mental status / meningeal signs  |  "
            "Failure to respond to >2 antibiotic courses  |  Anatomic abnormality / nosocomial infection  |  "
            "Immunocompromised  |  Unusual / resistant pathogens  |  Fungal sinusitis / granulomatous disease  |  "
            "Recurrent episodes suggesting CRS (this patient ✓)",
            S("ref", fontName="Helvetica", fontSize=7.5, textColor=BLACK, leading=9.5, alignment=TA_JUSTIFY)
        )
    ]]
]
refer_tbl = Table(refer_data, colWidths=[FULL_W])
refer_tbl.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,0), colors.HexColor("#7B1515")),
    ("BACKGROUND", (0,1), (-1,1), colors.HexColor("#FFF0F0")),
    ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
    ("TOPPADDING", (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING", (0,0), (-1,-1), 6),
    ("RIGHTPADDING", (0,0), (-1,-1), 6),
    ("BOX", (0,0), (-1,-1), 1, colors.HexColor("#7B1515")),
]))
story.append(refer_tbl)
story.append(Spacer(1, 2*mm))

# ══════════════════════════════════════════════════════════════════════════════
# FOOTER
# ══════════════════════════════════════════════════════════════════════════════
footer_data = [[
    Paragraph(
        "<b>Sources:</b> Goldman-Cecil Medicine (Intl Ed.) Ch.394 • Cummings Otolaryngology HNS Ch.29,35 • "
        "Scott-Brown's ORL Vol.1&2 • EPOS Guidelines • "
        "Cai S et al. <i>Allergy</i> 2025 [PMID:39985317] • Lipworth BJ et al. <i>NEJM</i> 2025 [PMID:40106374]",
        S("foot", fontName="Helvetica", fontSize=6.5, textColor=colors.HexColor("#555555"), leading=9, alignment=TA_CENTER)
    ),
    Paragraph(
        "<b>Orris MD Reference</b> | June 2026",
        S("foot2", fontName="Helvetica-Bold", fontSize=6.5, textColor=colors.HexColor("#555555"), leading=9, alignment=TA_CENTER)
    ),
]]
footer_tbl = Table(footer_data, colWidths=[FULL_W*0.78, FULL_W*0.22])
footer_tbl.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), LIGHT_GREY),
    ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
    ("TOPPADDING", (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING", (0,0), (-1,-1), 6),
    ("RIGHTPADDING", (0,0), (-1,-1), 6),
    ("BOX", (0,0), (-1,-1), 0.5, MID_GREY),
]))
story.append(footer_tbl)

# ── Build ──────────────────────────────────────────────────────────────────────
doc.build(story)
print("PDF generated successfully.")

Running Command

cd /home/daytona/workspace/sinusitis-flowchart && python generate_flowchart.py 2>&1

Running Command

ls -lh /home/daytona/workspace/sinusitis-flowchart/

The PDF has been generated successfully (13 KB, single A4 page). Here's your download link:

Sinusitis Management Flowchart

PDF Document · PDF

What's inside the flowchart (single A4, print-ready):

Section	Content
Title Banner	Patient profile: 30F, recurrent sinusitis, ↑IgE, B/L turbinate hypertrophy
Step 1	CRS diagnostic criteria (EPOS) + full differential diagnosis table
Step 2	Investigations - allergy workup, nasal/imaging, and lab panel (side-by-side)
Step 3	Allergen avoidance - HDM, moulds, pollens, pets
Step 4	Pharmacotherapy stepwise table - antihistamines → INCS (gold standard with doses) → LTRAs → saline → decongestants → OCS → antibiotics
Step 5	Immunotherapy - SCIT vs SLIT, indications, contraindications
Step 6	Surgical options (turbinate reduction techniques + FESS) + Biologics table (Dupilumab, Omalizumab, Mepolizumab, Tezepelumab)
Emergency Refer Box	ENT referral criteria (red-flag conditions)
Footer	Full source citations including 2025 NEJM + Allergy meta-analysis

Color-coded by severity tier (blue → green → amber → red) with directional arrows between each step.

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