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Treatment Profile: Tinea (Ringworm / Dermatophytosis)

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Diagnosis Before Treatment

• KOH preparation: Scrape the leading edge of the lesion; examine for hyphae and arthroconidia (sensitivity 77-88%). This should be confirmed before prescribing oral agents.
• Culture: Definitive but slow.
• PAS stain: Used on nail clippings for onychomycosis.
• Wood's lamp: Microsporum species fluoresce green-yellow; Trichophyton does not.

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Treatment by Site

1. Tinea Corporis (Body Ringworm)

• Applied twice daily for 2-4 weeks (continue 1 week beyond clinical resolution)
• Allylamines are preferred over azoles for higher cure rates:
  • Terbinafine 1% cream - once daily for 7 days; mycologic cure ~84% vs. 23% placebo
  • Naftifine, butenafine - also fungicidal (faster, shorter courses)
• Azoles (fungistatic, less expensive):
  • Clotrimazole, miconazole, ketoconazole, econazole, oxiconazole - twice daily x 2-4 weeks

• Terbinafine 250 mg/day x 1-2 weeks - higher cure rates than griseofulvin
• Itraconazole 100-200 mg/day x 1-2 weeks
• Griseofulvin (micro 500 mg/day or ultramicro 375 mg/day x 2-4 weeks)

Key: Allylamines outperform azoles for cure rates (SOR: A). Terbinafine 1% once daily for 7 days is highly effective (SOR: B). - Textbook of Family Medicine 9e

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2. Tinea Pedis (Athlete's Foot)

• Allylamines cure slightly more infections than azoles but cost more (SOR: A)
  • Terbinafine 1% or butenafine 1% twice daily x 1-2 weeks
  • Naftifine twice daily x 2-4 weeks
• Azoles: clotrimazole, miconazole, econazole twice daily x 2-4 weeks
• Keep feet dry; change socks frequently; avoid occlusive footwear; wear protective footwear in shared areas

• Terbinafine 250 mg/day x 2 weeks (SOR: B)
• Itraconazole 200 mg/day x 1 week
• Note: Tinea pedis often requires longer treatment and frequently relapses. - Harrison's 22E

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3. Tinea Cruris (Jock Itch)

• Same topical regimen as tinea corporis and pedis
• Treat the feet simultaneously if also infected (common co-infection source)
• Avoid tight or wet clothing; plain/antifungal powder may help reduce moisture
• Oral therapy if spread beyond the groin:
  • Terbinafine 250 mg/day x 1-2 weeks
  • Fluconazole 150 mg once weekly x 2-4 weeks (SOR: B)
  • Itraconazole as alternative

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4. Tinea Capitis (Scalp Ringworm)

• Griseofulvin: proven first-line, but requires longer courses; GI distress, headache, urticaria are common side effects
• Terbinafine granules: FDA-approved for tinea capitis; fewer drug interactions than itraconazole
• Kerion (boggy inflammatory mass): treat with oral antifungals; add a short oral steroid course if no response (does NOT require antibiotics or I&D)
• Use selenium sulfide 2.5% or ketoconazole 2% shampoo as adjunct to reduce shedding and transmission

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5. Onychomycosis / Tinea Unguium (Nail Ringworm)

• Ciclopirox 8% lacquer daily x 48 weeks
• Efinaconazole 10% solution or tavaborole 5% solution (FDA-approved, newer options)
• Amorolfine nail lacquer (available outside US)

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Oral Agent Summary

"Nizoral [ketoconazole] oral tablets should not be a first-line treatment for any fungal infection." - FDA warning, cited in Harrison's 22E

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General Principles

• Nystatin is NOT active against dermatophytes - do not use for tinea
• All oral agents carry hepatotoxicity risk - avoid in pregnancy and breastfeeding
• Verify fungal etiology (KOH or culture) before prescribing oral antifungals
• Prevent spread: avoid sharing towels/clothing, treat contacts, disinfect fomites
• Tinea versicolor (Malassezia furfur, not a true dermatophyte): treat with selenium sulfide, ketoconazole 2% shampoo, or short-course oral fluconazole/ketoconazole
• Watch for id reactions: papular/vesicular hypersensitivity remote from the infection site, often after starting treatment - not an allergy to the antifungal

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Treatment Profile: Eczema (Atopic Dermatitis)

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Pathophysiology Basis for Treatment

• Impaired epidermal barrier (filaggrin loss-of-function) allows allergen penetration and water loss
• Th2 cytokines IL-4 and IL-13 drive IgE production, eosinophil recruitment, and itch
• S. aureus colonization is near-universal in moderate-severe disease and acts as a superantigen trigger
• The "atopic march": AD often precedes asthma and allergic rhinitis

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Diagnostic Criteria

• Generalized dry skin in the past year
• History of asthma or hay fever (or atopic disease in a first-degree relative in children <4 years)
• Onset of rash before age 2
• Flexural dermatitis (or cheek/forehead involvement in children <4 years)

• Infants: cheeks, extensor surfaces, diaper area
• Children/Adults: flexural areas (antecubital and popliteal fossae), neck, upper chest

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Treatment Ladder

Step 1 - Skin Care Foundation (All Severity Levels)

• Apply oils, ointments, creams, or lotions multiple times daily
• In some cases, emollients are as effective as topical steroids for mild disease
• Apply immediately after bathing ("soak and smear" technique) to lock in moisture
• Reduce bathing water temperature; avoid harsh soaps; use fragrance-free products

• Heat, sweating, stress, wool clothing, aeroallergens, food allergens (in selected cases)
• Keep the sleeping environment cool; trim nails short to reduce scratch damage

• Written action plans outlining a stepwise approach are proven effective
• Psychological support is important - the disease significantly impacts quality of life and family sleep

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Step 2 - Topical Anti-inflammatory Agents (Mild-Moderate Disease)

Topical Corticosteroids (TCS)

• Fluorinated steroids must NOT be used on the face - they cause cutaneous atrophy
• Use mid-to-low potency on face, neck, and skin folds
• Apply once or twice daily; taper to the lowest effective potency
• If a patient worsens despite TCS + emollients, consider allergic contact dermatitis to a preservative or the steroid itself

Topical Calcineurin Inhibitors (TCIs)

• Tacrolimus ointment 0.03% (children) and 0.1% (adults) - twice daily
• Pimecrolimus cream 1% - twice daily
• Mechanism: inhibit calcineurin, blocking T-cell activation
• No risk of skin atrophy - safe for long-term use on face/intertriginous areas
• Side effect: transient stinging/burning on application; FDA black box warning about theoretical malignancy risk (weak evidence, not confirmed)

Topical Phosphodiesterase-4 (PDE4) Inhibitor

• Crisaborole 2% ointment - applied twice daily
• Non-steroidal; approved for mild-to-moderate AD in patients ≥3 months
• Side effect: application site pain/stinging

Topical JAK Inhibitor

• Ruxolitinib cream 1.5% - twice daily; approved for mild-to-moderate AD in patients ≥12 years
• Rapid onset; not for use on large body surface areas

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Step 3 - Antipruritic Agents

• Oral antihistamines (sedating: hydroxyzine, diphenhydramine) help with nocturnal itch via sedation
• Non-sedating antihistamines have limited benefit for AD itch (itch is not histamine-mediated)
• Most useful for helping patients sleep during flares

• "Soak and smear" (wet wrap therapy): apply topical steroid, cover with wet bandage then dry layer
• First-line for acute severe flares; 3-4 days often breaks a severe flare
• Especially effective in children

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Step 4 - Phototherapy (Moderate-Severe, Refractory to Topicals)

• Introduce at very low starting doses in AD (more sensitive than psoriasis patients)
• Acutely inflamed skin may tolerate UV poorly - cool with steroids first before starting

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Step 5 - Systemic Biologics (Moderate-Severe, Inadequate Topical Response)

Dupilumab (Dupixent) - FIRST-LINE BIOLOGIC

• Mechanism: Human monoclonal antibody targeting IL-4 receptor alpha subunit; blocks both IL-4 and IL-13 signaling
• Approved for: Patients ≥6 months with moderate-to-severe AD not adequately controlled with topicals
• Dosing:
  • Adults: 600 mg loading dose SC, then 300 mg every 2 weeks
  • Pediatric (weight-tiered): 200-600 mg loading, then 200-300 mg every 2-4 weeks depending on weight
• Efficacy: ~40-50% of adolescents/adults achieve EASI-75 at 16 weeks on monotherapy; ~55-70% when combined with TCS
• Side effects: Injection site reactions (~10%), conjunctivitis (~10-25% in real-world use) - manage with topical lubricants; does NOT cause immunosuppression; vaccine responses preserved; skin infections (including eczema herpeticum) actually decrease with dupilumab

Tralokinumab (Adbry)

• Mechanism: Binds free IL-13, blocking interaction with IL-13Rα1 and IL-13Rα2
• Approved for: Adults with moderate-to-severe AD
• Efficacy: ~30% EASI-75 monotherapy; ~55% with TCS at 16 weeks
• Side effects: Similar to dupilumab (conjunctivitis)

Lebrikizumab

• Mechanism: Binds soluble IL-13; blocks IL-4Rα heterodimerization
• Approved for: Adolescents and adults with moderate-to-severe AD
• Efficacy: ~55% EASI-75 in RCTs; sustained efficacy at 52 weeks

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Step 6 - Oral JAK Inhibitors (Moderate-Severe, Inadequate Response to Other Systemics)

• Onset: Rapid - itch reduction in 1-2 weeks, skin improvement in 2-4 weeks
• Efficacy: Upadacitinib 15 mg achieves EASI-75 in ~65% at 16 weeks; 30 mg in ~75%
• Monitoring required: CBC, lipids, LFTs, infection screen (including TB)
• Adverse effects: Acne, herpes zoster, serious bacterial infections, thrombosis, hyperlipidemia, major cardiovascular events, gastrointestinal perforation (upadacitinib/baricitinib)
• Black box warning: Increased risk of serious infection, malignancy, and cardiovascular events (class effect)

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Step 7 - Conventional Immunosuppressants (Off-label, Moderate-Severe)

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Systemic Corticosteroids (Use with Extreme Caution)

• Avoid for chronic AD - rebound flare on cessation is common and often worse than baseline
• Short courses (≤3 weeks) acceptable for acute exacerbations only, as a bridge
• If repeated courses required, step up to phototherapy or biologic
• Long-term risks: striae, infections, bone loss, growth delay in children
• Taper carefully and overlap with intensified topical regimen

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Managing Infectious Complications

• S. aureus (most common trigger/colonizer): topical mupirocin for localized impetiginization; oral flucloxacillin/cephalexin for widespread secondary infection; consider decolonization with dilute bleach baths (sodium hypochlorite 0.005% - half-teaspoon household bleach in 4L bath water)
• Eczema herpeticum (HSV superinfection): treat urgently with oral/IV acyclovir; may require hospitalization; do not use topical steroids on active herpes lesions
• Molluscum contagiosum / flat warts: use physical methods (curettage, cryotherapy) rather than chemical agents which irritate AD skin
• Smallpox vaccination is CONTRAINDICATED in AD patients - risk of progressive vaccinia

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Special Populations

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Key Evidence Highlights

• 2024 JAMA Dermatology living systematic review (PMID 39018058) of systemic immunomodulatory treatments confirms dupilumab and JAK inhibitors as superior to conventional immunosuppressants for moderate-severe AD
• 2024 AAD Practice Guideline (PMID 37943240) for adults: phototherapy and systemic therapies - dupilumab is preferred first-line systemic agent

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Treatment Profile: Diabetes Mellitus - Clinical Overview

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Glycemic Targets (All Types)

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Type 1 Diabetes Mellitus (T1DM)

Pathophysiology

Insulin Regimens

Basal-Bolus (Intensified) - Gold Standard

Premixed Insulins

• e.g., 70/30 (70% NPH / 30% regular) - less flexible; before breakfast and dinner
• Less preferred for T1DM due to rigidity

Insulin Pump (Continuous Subcutaneous Insulin Infusion, CSII)

• Uses only rapid-acting insulin continuously
• Best glycemic control with lowest hypoglycemia if combined with continuous glucose monitoring (CGM)

Adjunct Therapies in T1DM (Off-label / Conditional)

• Pramlintide (amylin analog): reduces postprandial glucose excursions and weight; SC injection with meals
• SGLT2 inhibitors: modest HbA1c reduction but risk of euglycemic DKA - use with caution
• Metformin: may reduce insulin dose and weight but not glycemic control specifically

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Type 2 Diabetes Mellitus (T2DM)

Step 1 - Lifestyle Modification (Mandatory Foundation)

• Diet: Mediterranean diet is most evidence-based (PREDIMED trial: 31% CV event reduction); reduce refined carbohydrates, saturated fats, sodium (<2300 mg/day); increase fiber, vegetables, whole grains
• Exercise: ≥150 min/week moderate-vigorous activity + strength training 3-4x/week
• Weight loss: Even 5-10% body weight loss significantly improves glycemic control
• Alcohol: ≤1 drink/day (women), ≤2/day (men) - or avoid entirely
• Lifestyle alone can achieve HbA1c reduction of 1-2% and delay need for medication

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Step 2 - Pharmacotherapy Algorithm for T2DM

First-Line: Metformin

• Metformin has been used for over 5 decades as first-line and remains preferred where cost/access is a concern
• 26-77% reduction in new-onset T2D in prediabetes

Add-on Therapy: Driven by Comorbidities

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Step 3 - Insulin in T2DM

1. Basal insulin first: Add long-acting insulin (glargine, detemir, or degludec) at bedtime - 10 units or 0.1-0.2 units/kg. Titrate fasting glucose to target.
2. If inadequate: Add prandial insulin before the largest meal (basal-plus), then convert to full basal-bolus.
3. Premixed insulins (70/30 before breakfast and dinner): simpler but less flexible.
4. Continue metformin with insulin (proven additive benefit, reduces insulin dose, weight).
5. Continuing GLP-1 RAs with insulin reduces weight gain and hypoglycemia.

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Acute Complications

Hypoglycemia

• Most common complication of insulin and sulfonylurea therapy
• Mild (conscious patient): 15 g fast-acting glucose (dextrose tablets, juice, glucose gel); recheck in 15 min ("15-15 rule")
• Severe (unconscious): Glucagon 1 mg SC/IM or intranasal glucagon (3 mg) - or IV 50% dextrose 20-50 mL bolus (EMS)
• Hypoglycemic unawareness: restore by avoiding tight glycemic control for weeks

Diabetic Ketoacidosis (DKA) - Primarily T1DM

1. IV fluids: 0.9% NaCl 1-2 L in first hour, then 250-500 mL/hr
2. Insulin: Regular insulin infusion 0.1 units/kg/hr IV; switch to SC when pH >7.3, ketones cleared, patient eating
3. Potassium: Replace aggressively (insulin drives K+ intracellularly; hold insulin if K+ <3.5 mEq/L)
4. Bicarbonate: Only if pH <6.9
5. Identify and treat precipitant (infection, missed insulin, MI)

Hyperosmolar Hyperglycemic State (HHS) - Primarily T2DM

• Severe hyperglycemia (>600 mg/dL), hyperosmolality, minimal ketosis
• Treatment: Slow fluid replacement (0.45% NaCl typically); low-dose insulin infusion; correct electrolytes

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Chronic Complications - Treatment Targets and Key Therapies

Diabetic Nephropathy

• ACE inhibitor or ARB: First-line for all diabetics with hypertension or albuminuria (nephroprotection regardless of BP effect)
• SGLT2 inhibitors: Canagliflozin and dapagliflozin reduce CKD progression and ESKD (CREDENCE, DAPA-CKD)
• Finerenone (non-steroidal MRA): approved for CKD + T2DM; reduces CV events and kidney failure
• Avoid nephrotoxins (NSAIDs, contrast without adequate hydration)
• Hold metformin if eGFR <30; dose-reduce if 30-45

Diabetic Neuropathy

• Glycemic control is the only proven measure to prevent/slow progression
• Pain management:
  • First-line: Pregabalin (75-300 mg BD) or duloxetine (60-120 mg/day) - both FDA-approved for diabetic neuropathic pain
  • Second-line: Gabapentin, tricyclic antidepressants (amitriptyline, nortriptyline)
  • Topical: Capsaicin 8% patch or lidocaine patches for localized pain
  • Opioids: last resort only

Diabetic Retinopathy

• Annual dilated fundoscopic exam for all T1DM (after 5 years) and T2DM (at diagnosis)
• Tight glycemic and BP control slows progression (DCCT, UKPDS)
• Laser photocoagulation: Proliferative retinopathy and macular edema
• Anti-VEGF injections (ranibizumab, bevacizumab): for diabetic macular edema - superior to laser
• Fenofibrate: Reduces retinopathy progression in T2DM (FIELD, ACCORD-Eye)

Diabetic Foot

• Regular foot examination: Monofilament testing, ankle-brachial index (ABI)
• Offloading: Total contact casting for neuropathic ulcers
• Wound care: Debridement, moist wound dressings, infection control
• Antibiotics: Empiric coverage for Staph/Strep (infected wounds); broader for severe/ischemic infections
• Revascularization: For peripheral arterial disease contributing to non-healing wounds
• Vaccinations: influenza, pneumococcal, hepatitis B (all diabetic patients)

Cardiovascular Risk Reduction (Essential in All Diabetics)

• Statins: All T2DM patients >40 years or with CVD risk - high-intensity statin (atorvastatin 40-80 mg or rosuvastatin 20-40 mg)
• Aspirin 75-100 mg/day: Secondary prevention only (established CVD); primary prevention only if high CV risk and no bleeding risk
• BP control: RAAS blockade preferred (ACE inhibitor or ARB); target <130/80 mmHg
• Smoking cessation: Strongest modifiable CV risk factor

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Monitoring

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Special Considerations

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Diabetic Ketoacidosis (DKA): Complete Criteria, Diagnosis, and Treatment

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Definition

1. Ketonemia / ketonuria (ketosis)
2. Hyperglycemia (or history of diabetes)
3. Metabolic acidemia (anion gap acidosis)

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Pathophysiology

Insulin deficiency + Glucagon excess
         │
         ├─► Lipolysis ──► Free fatty acids ──► Liver ──► Acetoacetate + β-hydroxybutyrate
         │                                              ──► Acetone (fruity breath)
         │
         ├─► Gluconeogenesis + Glycogenolysis ──► Hyperglycemia
         │
         └─► Osmotic diuresis ──► Dehydration + Electrolyte loss (Na, K, Mg, PO4, Cl)

• Ketoacids lower HCO3⁻, raise the anion gap → high anion gap metabolic acidosis
• In early/mild DKA (normal volume): ketoacids excreted as Na⁺/K⁺ salts → normal anion gap (hyperchloremic) acidosis
• As volume depletes, ketoacid excretion cannot keep pace → anion gap widens
• During treatment, anion gap acidosis converts back to hyperchloremic acidosis (normal gap) before full resolution - this is expected and not a sign of failure

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Precipitants ("The 6 I's" + drugs)

• Infection (most frequent - pneumonia, UTI, cellulitis)
• Inadequate insulin / non-adherence
• Initial presentation of new-onset T1DM

• Ischemia (ACS, stroke)
• Infarction/Inflammation (pancreatitis, mesenteric thrombosis)
• Intoxication (alcohol, cocaine)
• Drugs: Corticosteroids, SGLT2 inhibitors (euglycemic DKA), antipsychotics (clozapine, olanzapine), sympathomimetics, thiazide diuretics, lithium
• Endocrinopathies: Cushing's syndrome, thyrotoxicosis, acromegaly
• Severe burns, hyperthermia/hypothermia
• Emotional stress (despite continued insulin)

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Diagnostic Criteria

Biochemical Triad (The "DKA")

Note: The degree of hyperglycemia does NOT correlate with severity of acidosis. - Barash Clinical Anesthesia 9e

Severity Classification (ADA/2024 Consensus)

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Clinical Presentation

• Progressive polyuria and polydipsia
• Nausea, vomiting, anorexia
• Weakness, lethargy, malaise
• Diffuse abdominal pain (may mimic acute abdomen; from ileus/gastric paresis - NOT a surgical emergency unless confirmed)
• Fruity/acetone breath

• Kussmaul breathing (deep, labored, rapid respirations - respiratory compensation for acidosis)
• Dry skin and mucous membranes
• Reduced jugular venous pressure
• Tachycardia, orthostatic hypotension (hypovolemic shock in severe cases)
• Altered mental status, stupor, coma (correlates with hyperosmolality)
• Fever if infection is the precipitant (absence of fever does not rule out infection)

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Investigations (Initial Workup)

Mandatory (stat)

Additional (guided by clinical picture)

• Blood cultures (if infection suspected)
• Chest X-ray (pneumonia, aspiration)
• Troponin / ACS workup (if indicated)
• Corrected sodium: Add 1.6 mEq/L to measured Na⁺ for every 100 mg/dL glucose >100 mg/dL

Acid-Base Analysis Pearls

• Winter's Formula: Expected paCO2 = (1.5 × HCO3⁻) + 8 ± 2 - if actual paCO2 is higher than expected, concurrent respiratory acidosis; if lower, concurrent respiratory alkalosis
• Delta-delta gap: If delta AG - delta HCO3⁻ > +6 → concurrent metabolic alkalosis (e.g., from vomiting); if < -6 → concurrent hyperchloremic acidosis

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Treatment

Priority Order

1. Airway - avoid intubation if possible; if comatose/vomiting → intubate and maintain hyperventilation
2. IV fluids (first and most urgent)
3. Potassium replacement (before or with insulin unless K⁺ >5.5)
4. Insulin (only after K⁺ ≥3.5 mEq/L)
5. Find and treat the precipitant
6. Monitor closely with flow sheet (glucose, pH, K⁺, HCO3⁻, urine output hourly)

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1. Intravenous Fluids

2024 Meta-Analysis Update (PMID 38925619): Balanced electrolyte solutions (e.g., Plasmalyte, Hartmann's) result in faster DKA resolution than 0.9% saline (avoids hyperchloremic acidosis) - increasingly preferred over NS once shock phase is complete.

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2. Potassium Replacement

• Check K⁺ every 1-2 hours during treatment
• ECG monitoring is useful if rapid K⁺ measurement not immediately available

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3. Insulin

• If glucose not falling by ≥50-75 mg/dL/hr → double insulin infusion rate
• When glucose reaches 250-300 mg/dL → add dextrose to IV fluids AND reduce insulin to 0.05 units/kg/hr (keep insulin going to clear ketones)
• In euglycemic DKA → add dextrose to IV fluids from the start of insulin therapy

2026 Meta-Analysis (PMID 41208563): Adding early SC basal insulin alongside IV insulin infusion reduces rebound hyperglycemia after transition and may shorten ICU stay.

2024 Meta-Analysis (PMID 39090718): SC insulin protocols are non-inferior to continuous IV insulin for mild-moderate DKA in selected patients.

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4. Phosphate

• Not routinely replaced (randomized trials show no benefit in most patients)
• Replace if: Serum phosphate <1 mg/dL, or clinical signs of hypophosphatemia (respiratory muscle weakness, hemolytic anemia, altered mental status)
• Use potassium phosphate solution when both K⁺ and PO4²⁻ need replacement

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5. Magnesium

• Commonly depleted due to osmotic diuresis
• Hypomagnesemia → refractory hypokalemia and hypocalcemia, cardiac arrhythmias, worsened mental status, vomiting
• If symptomatic or Mg²⁺ low: 1-3 g magnesium sulfate IV over 1-2 hours

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6. Sodium Bicarbonate

• Worsening hypokalemia
• Paradoxical CSF acidosis (CO2 crosses blood-brain barrier faster than HCO3⁻)
• Delayed ketosis clearance
• No improvement in outcomes

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Resolution Criteria (DKA)

Important: Urine ketones may remain positive (especially nitroprusside-based tests) for hours after DKA has resolved, as acetoacetate is regenerated from β-hydroxybutyrate during recovery. This is expected and should NOT delay transition to SC insulin.

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Transition to Subcutaneous Insulin

1. Patient tolerating oral food/drink
2. DKA resolution criteria met (above)
3. Give SC basal insulin 1-2 hours BEFORE stopping IV insulin infusion (to prevent rebound hyperglycemia due to short half-life of IV insulin)
4. If new-onset T1DM: start basal-bolus regimen at 0.5-0.8 units/kg/day
5. If known T1DM: restart the patient's home insulin regimen
6. Identify and address the reason DKA occurred before discharge

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Monitoring During Treatment (Flow Sheet)

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Complications

Iatrogenic (most preventable)

Clinical

Mortality

• Treated DKA: 5-7% overall mortality
• Primary causes of death: infection (especially pneumonia), arterial thrombosis, shock
• Mortality has decreased significantly with standardized protocols

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DKA vs HHS - Key Distinctions

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Keratitis vs. Conjunctivitis: Key Differences with Images

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Anatomical Basis - Where Is the Inflammation?

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CONJUNCTIVITIS

Definition

Types and Clinical Features

1. Bacterial Conjunctivitis

• Symptoms: Painless or minimally painful; mucopurulent discharge causing eyelids to stick together on waking; gritty sensation
• Signs: Diffuse conjunctival injection; chemosis (conjunctival edema); cornea clear with no fluorescein staining; no preauricular lymphadenopathy (except gonococcal)
• Discharge: Yellow-green, mucopurulent, thick
• Pathogens: Staphylococcus, Streptococcus, H. influenzae; contact lens wearers → Pseudomonas
• Treatment: Topical trimethoprim-polymyxin B; fluoroquinolone drops for contact lens wearers; usually self-limited

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2. Viral Conjunctivitis

• Most common cause: Adenovirus (most frequent); also HSV, EBV, measles
• Symptoms: Watery, clear discharge; foreign-body sensation; mild photophobia; often bilateral (spreads from one eye to the other); may follow upper respiratory infection
• Signs: Diffuse injection, watery discharge, preauricular lymphadenopathy (distinguishes from bacterial), follicles on palpebral conjunctiva; cornea initially clear
• Epidemic keratoconjunctivitis (EKC): Severe adenoviral infection - intense redness, photophobia, subepithelial corneal infiltrates (punctate keratitis may develop)
• Treatment: Supportive - cool compresses, artificial tears, ocular decongestants (e.g., naphazoline); highly contagious - strict hand hygiene; resolves in 1-3 weeks

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3. Allergic Conjunctivitis

• Symptoms: Intense itching (the hallmark), watery discharge, redness, epiphora
• Signs: Injected, edematous conjunctiva; cobblestone papillae on palpebral conjunctiva (in vernal/chronic forms); prominent chemosis; cornea clear
• Discharge: Stringy, white, mucoid
• Treatment: Remove allergen; cool compresses; topical antihistamines (olopatadine); mast cell stabilizers (cromolyn); NSAIDs (ketorolac); topical steroids only for severe cases (with ophthalmology oversight)

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Image: Punctate keratitis - a complication when viral conjunctivitis spreads to the cornea

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KERATITIS

Definition

"Keratitis is a threat to vision because of the risk of corneal clouding, scarring, and perforation." - Harrison's 22E

Types and Clinical Features

1. Bacterial Keratitis

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• Symptoms: Severe unilateral pain, photophobia, blurred vision, mucopurulent or purulent discharge
• Signs: Epithelial defect + stromal infiltrate; circumcorneal (ciliary) injection (redness most intense around the cornea); stromal edema; anterior uveitis; hypopyon (pus in anterior chamber) in moderate-severe cases; chemosis and lid swelling
• Risk factors: Contact lens wear (especially extended use) - Pseudomonas is responsible for >60% of contact lens-related keratitis; corneal trauma; immunosuppression; diabetes; prior LASIK
• Pathogens: Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae, Moraxella

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2. Herpetic Keratitis (HSV)

• Pattern: Characteristic dendritic (branching) ulcer on cornea - pathognomonic for HSV keratitis
• Fluorescein staining reveals branching tree-like epithelial defect
• Can recur with stress/immunosuppression; repeated episodes cause progressive corneal scarring
• Treatment: Topical antiviral (ganciclovir gel or trifluridine); oral acyclovir/valacyclovir for stromal disease; never use topical steroids alone without antiviral cover (reactivates virus)

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3. Fungal Keratitis

• Typically gradual onset; grey or yellow-white infiltrate with indistinct fluffy margins and satellite lesions
• Associated with plant/agricultural trauma in tropical climates; contact lens wear; topical steroid use
• Filamentous fungi (Fusarium, Aspergillus) in tropics; Candida in temperate climates
• Can penetrate intact Descemet's membrane causing endophthalmitis without perforation
• Treatment: Topical natamycin (filamentous); topical/oral voriconazole; prolonged course

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4. Acanthamoeba Keratitis

• Associated with contact lens wear + tap water exposure (swimming, lens rinsing with tap water)
• Intensely painful, disproportionate to signs
• Ring infiltrate on cornea is characteristic
• Often misdiagnosed as HSV initially - delayed diagnosis leads to poor outcomes
• Treatment: Topical polyhexamethylene biguanide (PHMB) + propamidine for months

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Side-by-Side Comparison

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Diagnostic Red Flags: "This is NOT Simple Conjunctivitis"

1. Significant pain - especially if deep/boring
2. Reduced visual acuity
3. Marked photophobia
4. Circumcorneal (limbal) injection
5. Corneal haziness or white spot visible to naked eye
6. Hypopyon (white layer at bottom of iris)
7. Contact lens wearer - any red eye is bacterial keratitis until proven otherwise
8. Failure to improve after 48 hours of topical antibiotics

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Treatment Summary

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Migraine: Diagnostic Criteria and Treatment Profile

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Overview

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Pathophysiology (Brief)

• Cortical spreading depression (CSD) - the neurological basis of aura; a wave of depolarization spreading across the cortex at 3-5 mm/min
• Trigeminovascular activation - sensitization of trigeminal nerve fibers innervating meningeal vessels, releasing inflammatory mediators (including CGRP - calcitonin gene-related peptide) that drive the headache phase
• Central sensitization - explains cutaneous allodynia (skin sensitivity) and the "throbbing" quality

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The Four Phases of a Migraine Attack

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DIAGNOSTIC CRITERIA (ICHD-3)

Migraine Without Aura

1. Unilateral location (60-75% of cases; may become bilateral as attack progresses)
2. Pulsating/throbbing quality
3. Moderate or severe pain intensity (inhibits or prohibits daily activities)
4. Aggravation by routine physical activity (e.g., walking, climbing stairs), or causes avoidance of activity

1. Nausea and/or vomiting
2. Photophobia AND phonophobia

Memory aid: "POUND" - Pulsatile, One-day duration (4-72h), Unilateral, Nausea, Disabling

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Migraine With Aura

• Visual (most common: scintillating scotoma, zigzag lines/fortification spectra, visual field loss)
• Sensory (paresthesias - typically starting in hand, spreading to face)
• Speech and/or language (expressive dysphasia most common)
• Motor (hemiplegic migraine)
• Brainstem symptoms (dysarthria, vertigo, tinnitus, diplopia, ataxia)
• Retinal (monocular visual disturbance)

1. At least one aura symptom spreads gradually over ≥5 minutes
2. Two or more aura symptoms occur in succession
3. Each individual aura symptom lasts 5-60 minutes
4. At least one aura symptom is unilateral
5. At least one aura symptom is positive (e.g., zig-zag lines, tingling - not just loss)
6. Aura is accompanied, or followed within 60 minutes, by headache

Key: Aura spread is SLOW (5-20 min to reach maximum) - this distinguishes it from TIA (seconds) and seizure (seconds to 1-2 min)

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Special Migraine Subtypes

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Common Triggers

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TREATMENT

Key Principle: Stratified Care

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Acute (Abortive) Treatment

• Treat as early as possible - during aura if recognizable, not waiting for full pain
• Oral preparations become less effective once attack is fully established (GI dysmotility impairs absorption) - use non-oral routes for severe attacks
• Combine drugs with different mechanisms (NSAID + triptan + antiemetic) for more refractory attacks
• Rest in a dark, quiet room with ice pack; sleep often terminates attack

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Step 1: Mild-Moderate Attacks (Non-specific Analgesics)

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Step 2: Moderate-Severe Attacks (Migraine-Specific: Triptans)

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Step 2 Alternative: Lasmiditan (Reyvow)

• Selective 5-HT1F receptor agonist - NO vasoconstrictive properties
• Safe in patients with cardiovascular contraindications to triptans
• Efficacy comparable to triptans in Phase III trials
• Side effects: dizziness, sedation; do not drive for 8 hours after

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Step 2 Alternative: CGRP Receptor Antagonists (Gepants) - Acute Use

• Ubrogepant (Ubrelvy): 50-100 mg oral
• Rimegepant (Nurtec ODT): 75 mg ODT - also approved for prevention
• Mechanism: block CGRP receptor → no vasoconstrictive effects → safe in cardiovascular disease
• Effective; can be combined with triptans; no medication overuse headache risk (unlike triptans/NSAIDs)

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Ergot Derivatives (Second-line)

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Antiemetics (Adjunctive - Essential)

• Metoclopramide 10 mg IV/oral - dopamine antagonist; treats nausea AND improves GI motility (increases triptan absorption); mild efficacy against headache itself
• Prochlorperazine 10 mg IV/oral - effective antiemetic; IV prochlorperazine alone has significant intrinsic antimigraine efficacy (useful in ED)
• Ondansetron 4-8 mg - for refractory nausea; less efficacy against headache
• Chlorpromazine 0.1 mg/kg IV - effective for acute migraine in ED

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IV/ED Treatment for Severe/Status Migrainosus

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Preventive (Prophylactic) Treatment

When to Start Prevention

• ≥4 migraine days/month
• Attacks are very prolonged or debilitating even if infrequent
• Acute medications are contraindicated, ineffective, or overused
• Specific subtypes: hemiplegic migraine, migraine with prolonged aura, migrainous infarction
• Patient preference

Goals and Principles

• Reduce attack frequency by ≥50% (target)
• Titrate slowly to minimum effective/maximum tolerated dose
• Give each drug at least 3 months (full benefit may take 6 months)
• Discontinue after 6-12 months of good control and reassess
• Avoid in pregnancy (most agents teratogenic)

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First-Line Preventive Agents (AAN/AHS Level A)

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Second-Line Preventive Agents (AAN/AHS Level B-C)

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Newer Targeted Preventive Therapies - CGRP Pathway

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Botulinum Toxin (OnabotulinumtoxinA / Botox)

• FDA-approved for chronic migraine only (≥15 headache days/month)
• 155-195 units injected at 31-39 sites across head and neck muscles every 12 weeks
• Reduces headache days by ~8-9 days/month vs. ~6-7 placebo in PREEMPT trials
• Very safe; most common SE: neck pain, injection site reactions

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Non-Pharmacological Management

• Trigger identification and avoidance (keep headache diary)
• Regular sleep schedule - consistent wake/sleep times; avoid oversleeping
• Regular meals - avoid fasting; stay hydrated
• Aerobic exercise ≥3x/week - reduces migraine frequency comparably to some preventive drugs
• Cognitive-behavioral therapy (CBT) + biofeedback - Level A evidence for prevention
• Relaxation training - progressive muscle relaxation; mindfulness
• Physical therapy - for cervicogenic triggers and muscle tension
• Acupuncture - modest evidence; can be used as adjunct
• Neuromodulation devices (non-invasive): transcranial magnetic stimulation (sTMS; FDA-cleared for acute and preventive treatment), external trigeminal nerve stimulator (Cefaly), non-invasive vagus nerve stimulator (gammaCore)

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Medication Overuse Headache (MOH / "Rebound Headache")

• Develops when acute medications are taken too frequently:
  • Triptans/ergotamines: ≥10 days/month
  • NSAIDs/analgesics: ≥15 days/month
  • Opioids/combination analgesics: ≥10 days/month
• Features: Diffuse daily headache, worse on waking, analgesic tolerance, reduced response to preventive medications
• Treatment: Withdraw the overused medication (abrupt for triptans/NSAIDs; tapering for opioids/barbiturates/benzodiazepines); bridge with DHE protocol or steroids; restart preventive therapy

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Special Populations

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Diagnosis and Treatment of Other Types of Headache

• Primary headaches (no underlying cause - the headache IS the disease): Tension-type, cluster, trigeminal autonomic cephalalgias, other primary headaches
• Secondary headaches (caused by another condition): Subarachnoid hemorrhage, meningitis, increased ICP, cervicogenic, medication overuse, etc.

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1. TENSION-TYPE HEADACHE (TTH)

Diagnostic Criteria (ICHD-3)

1. Bilateral location
2. Pressing/tightening quality (non-pulsating) - "band-like," "vise around head," pressure
3. Mild to moderate intensity (does not prohibit activities)
4. NOT aggravated by routine physical activity (walking, climbing)

• No nausea or vomiting
• No more than one of: photophobia OR phonophobia (not both)

Key Distinguishing Features from Migraine

Pathophysiology

Treatment

• Acetaminophen 1000 mg - first-line, well-tolerated
• Ibuprofen 400-800 mg or naproxen 500-1000 mg - effective
• Aspirin 500-1000 mg
• Caffeine combination products (aspirin/acetaminophen + caffeine) - modestly more effective
• Rest, ice/heat pack, massage of neck/scalp muscles
• Triptans are NOT effective for pure TTH (only effective if comorbid migraine)
• Opioids are never indicated - if parenteral treatment seems needed, reconsider the diagnosis

• Amitriptyline 10-75 mg/night - the only drug with proven efficacy (even in non-depressed patients); benefit independent of antidepressant effect
• Nortriptyline - better tolerated than amitriptyline
• SSRIs and benzodiazepines have NOT been shown effective for chronic TTH
• OnabotulinumtoxinA (Botox) - negative in controlled trials for TTH (unlike chronic migraine)
• Acupuncture - modest benefit for some patients
• Biofeedback + relaxation therapy - effective for prevention
• Address underlying anxiety, depression, stress - critical for chronic TTH management
• Avoid analgesic overuse (>15 days/month leads to medication overuse headache)

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2. TRIGEMINAL AUTONOMIC CEPHALALGIAS (TACs)

• Unilateral, severe orbital/periorbital pain
• Ipsilateral cranial autonomic features (lacrimation, conjunctival injection, rhinorrhea, nasal congestion, ptosis, miosis, facial sweating)
• Short-to-moderate duration attacks

TAC Comparison Table (ICHD-3 / Harrison's 22E)

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2A. Cluster Headache

• ≥5 attacks of severe/very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15-180 min
• At least 1 of: ipsilateral conjunctival injection/lacrimation, nasal congestion/rhinorrhea, eyelid edema, forehead/facial sweating, miosis/ptosis, or restlessness/agitation
• Attacks cluster in bouts (episodic: 7 days-1 year, followed by ≥3-month remission; chronic: no remission >3 months)
• 1-8 attacks per 24 hours; often nocturnal (1-2 hrs after sleep onset / REM sleep)

• Prevalence ~1 in 500; predominantly males (3:1), onset 3rd decade
• ~90% episodic; ~10% chronic
• Attacks peak in 5-10 min; patient is agitated and restless (opposite to migraine - patients pace and rock)

Acute Treatment of Cluster Headache

Preventive Treatment of Cluster Headache

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2B. Paroxysmal Hemicrania (PH)

• Short (2-30 min) attacks of severe unilateral periorbital pain, multiple times daily
• Associated with full ipsilateral autonomic features
• Absolute and complete response to indomethacin is pathognomonic and diagnostic
  • Start 25 mg TID with food; titrate to 75-150 mg/day until complete resolution
  • Cover with PPI to protect gastric mucosa
• Failure to respond to indomethacin should prompt search for secondary cause (structural lesion)

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2C. SUNCT / SUNA

• Short-lasting Unilateral Neuralgiform headache with Conjunctival injection and Tearing (SUNCT) or Cranial Autonomic symptoms (SUNA)
• Ultra-short attacks (5-240 seconds); frequency 3-200/day
• Triggered by cutaneous stimuli (unlike trigeminal neuralgia, brief refractory period between attacks)
• Acute: IV lidocaine for severe attacks
• Preventive: Lamotrigine (150 mg/day - first-line), topiramate, gabapentin
• Must rule out posterior fossa / pituitary lesions with MRI

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2D. Hemicrania Continua

• Continuous unilateral headache with fluctuating severity; background pain with superimposed exacerbations
• Ipsilateral autonomic features during exacerbations
• Absolute, complete response to indomethacin (same as PH - diagnostic)
• Treatment: indomethacin 75-150 mg/day indefinitely; COX-2 inhibitors as alternative to spare GI side effects; topiramate or melatonin for indomethacin-intolerant patients

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3. TRIGEMINAL NEURALGIA (Tic Douloureux)

Diagnosis

• Sudden, brief (seconds to <2 min), severe, electric shock-like stabbing pain in trigeminal nerve distribution (V2 and V3 most common - cheek, jaw, gums, lips)
• Triggered by light touch of specific trigger zones (eating, talking, cold wind, brushing teeth)
• Pain-free interval between attacks (refractory period - key distinction from SUNCT)
• Usually unilateral; affects women > men; most common >50 years
• Most cases: neurovascular compression of the trigeminal nerve root (superior cerebellar artery)
• Red flag: Bilateral TN or TN in a young patient → rule out multiple sclerosis

Investigation

• MRI with contrast - to rule out secondary causes (MS plaques, tumor, vascular compression)

Treatment

• Microvascular decompression (MVD) - most durable; Teflon felt placed between nerve and offending vessel; gold standard for fit surgical candidates
• Stereotactic radiosurgery (Gamma Knife) - less invasive; 1-2 month latency; for poor surgical candidates
• Percutaneous procedures (balloon compression, glycerol rhizotomy, radiofrequency thermocoagulation) - less durable but fast onset

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4. OTHER PRIMARY HEADACHES

Primary Thunderclap Headache (Benign)

• Sudden-onset severe headache reaching max intensity in <1 minute; lasts hours to days
• Must first rule out subarachnoid hemorrhage - this is a diagnosis of exclusion
• Once secondary causes excluded: typically spontaneously resolves; NSAIDs for pain; nimodipine may help in primary cases

Primary Cough Headache

• Bilateral headache precipitated by and lasting <30 min after coughing/Valsalva
• Must exclude Arnold-Chiari malformation with MRI
• Treatment: indomethacin 25-75 mg/day; propranolol; acetazolamide

Primary Exertional Headache

• Bilateral, pulsating headache during/after physical exertion, lasting 5 min to 48 hours
• Must exclude subarachnoid hemorrhage for first attack
• Treatment: indomethacin pre-exercise; propranolol; ergotamine before anticipated exercise

Primary Sex Headache (Coital Headache)

• Bilateral headache precipitated by sexual activity; two forms: dull ache building with arousal (tension-type), or explosive at orgasm
• Explosive type must urgently exclude SAH
• Treatment: indomethacin 25-50 mg before sexual activity; propranolol; triptan before anticipated sexual activity

New Daily Persistent Headache (NDPH)

• Daily headache from onset (no prior history), memorable first day, persistent from the start
• Often follows viral illness; distinct from chronic migraine/TTH
• Treatment: notoriously refractory; tricyclics, topiramate, doxycycline (anti-inflammatory); spontaneous remission in some

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5. SECONDARY HEADACHES - RED FLAGS AND KEY Diagnoses

"SNOOP4" - Red Flag Criteria (Prompt investigation)

Key Secondary Headache Diagnoses

Subarachnoid Hemorrhage (SAH)

• "Worst headache of my life" - thunderclap onset, reaching maximum severity within seconds to 1 minute
• May follow exertion; associated neck stiffness, photophobia, vomiting, loss of consciousness
• Investigation: Non-contrast CT head (sensitivity ~98% within 6 hrs; drops with time); if CT negative → lumbar puncture (xanthochromia); CT angiography/MR angiography for aneurysm
• Treatment: Neurosurgical emergency - coiling or clipping of aneurysm; nimodipine 60 mg every 4 hours (reduces vasospasm); ICU care

Meningitis/Encephalitis

• Headache + fever + neck stiffness + photophobia = meningism triad
• Kernig's sign (can't extend knee when hip flexed 90°), Brudzinski's sign (involuntary hip/knee flexion on neck flexion)
• Investigation: LP (after CT to exclude raised ICP); CSF analysis (opening pressure, cell count, glucose, protein, Gram stain, culture, PCR for viruses)
• Treatment: Immediate empiric: ceftriaxone 2g IV BD + dexamethasone 0.15 mg/kg IV QDS before LP if suspected bacterial; add acyclovir 10 mg/kg TID for HSV encephalitis

Giant Cell Arteritis (Temporal Arteritis)

• Age >50 (almost always >60); new headache, scalp tenderness, jaw claudication, visual disturbance
• Tender, nodular, non-pulsatile temporal artery; elevated ESR and CRP
• Risk of sudden permanent visual loss (anterior ischemic optic neuropathy)
• Investigation: ESR (often >50 mm/hr), CRP, temporal artery biopsy
• Treatment: Immediate high-dose prednisone 40-60 mg/day even before biopsy if visual symptoms (do not wait); if visual loss threatened: IV methylprednisolone 1g/day × 3 days; tocilizumab (IL-6 receptor antagonist) now approved as steroid-sparing agent

Idiopathic Intracranial Hypertension (IIH / Pseudotumor Cerebri)

• Obese young women; daily headache, visual obscurations, pulsatile tinnitus, papilledema
• Investigation: MRI (empty sella, transverse sinus stenosis, optic nerve sheath dilation); LP shows raised opening pressure (>25 cmH2O), normal CSF constituents
• Treatment: Acetazolamide 1-4 g/day (reduces CSF production); weight loss; repeat LP for symptom relief; optic nerve sheath fenestration or CSF shunting for vision-threatening cases

Cervicogenic Headache

• Headache originating from cervical structures; unilateral, radiates from occiput to forehead; associated with neck pain and restricted cervical ROM; worsened by neck movements/positions
• Investigation: Cervical spine imaging; diagnostic nerve blocks
• Treatment: Physical therapy; cervical nerve blocks; NSAIDs; trigger point injections; surgery for structural pathology

Post-traumatic Headache

• Develops within 7 days of head trauma; resembles migraine or TTH
• Duration varies - may persist for months to years
• Treatment: Amitriptyline or other migraine/TTH preventives; NSAIDs/triptans for acute episodes; avoid opioids; address psychological comorbidity

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Quick Summary Table

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Herpes: Diagnosis and Treatment

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PART 1: HERPES SIMPLEX VIRUS (HSV)

Virology and Epidemiology

• HSV-1: Double-stranded DNA virus; seroprevalence ~58-90% worldwide. Primary cause of orolabial herpes (80%) and HSV encephalitis.
• HSV-2: Primary cause of genital herpes (70-90%); seroprevalence ~17% in the US aged 14-49 years. ~50 million Americans affected; ~1 million new genital herpes cases per year.
• Transmission: HSV-1 via oral secretions/contact; HSV-2 via sexual/genital contact or neonatal during delivery.
• After primary infection, virus travels retrograde to sensory nerve root ganglia (trigeminal ganglion for HSV-1; sacral ganglia S2-S4 for HSV-2) where it remains latent for months to years.
• Reactivation triggers: Fever, emotional stress, trauma, intense sunlight, immunosuppression, menstruation.

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Clinical Syndromes and Diagnosis

1A. Oral / Orolabial Herpes (HSV-1)

• Incubation: 3-7 days after exposure
• Prodrome: fever, sore throat, cervical lymphadenopathy, malaise
• Painful grouped vesicles on erythematous base anywhere in the oral mucosa, gums, pharynx
• Lesions ulcerate, coalesce, then heal in 2-3 weeks
• Most common in young children; painful eating/drooling common

• Prodrome: tingling, burning, pruritus at the lip vermilion border (hours before lesions)
• Small clusters of vesicles at the vermilion border of the lip → crust within 48 hours
• Milder and shorter than primary; self-limiting in 7-10 days

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1B. Genital Herpes (HSV-2 >> HSV-1)

• Incubation: up to 3 weeks after sexual contact
• More severe than oral primary infection
• Systemic: fever, malaise, myalgia, headache
• Men: painful vesicles/ulcers on penis, buttocks, perineum
• Women: vesicles/ulcers on labia, cervix, buttocks, perineum; more severe - vaginal discharge, dysuria, inguinal lymphadenopathy
• Duration: 2-3 weeks

• Prodrome of itching, tingling, burning/paresthesias precedes lesions by hours
• Less severe and shorter (7-10 days) than primary
• Asymptomatic viral shedding between outbreaks - major source of transmission

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1C. Herpes Simplex Encephalitis (HSV-1)

• Most common sporadic viral encephalitis in adults
• Necrotizing hemorrhagic encephalitis of the temporal lobes
• Features: acute fever, headache, altered mental status, seizures, focal neurological deficits (temporal lobe involvement: aphasia, behavioral change)
• Untreated mortality >70% - medical emergency
• MRI: T2/FLAIR hyperintensity in temporal and frontal lobes
• LP: lymphocytic pleocytosis, elevated protein, normal glucose; HSV PCR on CSF (sensitivity ~98%)
• Treatment: Acyclovir IV 10 mg/kg every 8 hours × 14-21 days - start empirically before PCR result

1D. Herpes Meningitis (HSV-2)

• Occurs in >25% of patients with primary HSV-2 infection, more common in women
• Benign, self-limiting course (unlike encephalitis)
• Lymphocytic meningitis; HSV-2 PCR on CSF diagnostic

1E. Herpetic Whitlow

• HSV infection of the finger (paronychia-like)
• Occurs in healthcare workers (oral contact) or autoinoculation
• Painful vesicles on finger; self-limiting but antiviral therapy shortens course

1F. Herpes Keratitis

• HSV-1 causing corneal ulceration; dendritic (branching) ulcer on fluorescein slit-lamp examination
• Leading infectious cause of corneal blindness in developed countries
• Treatment: Topical acyclovir 3% ointment 5×/day, or topical ganciclovir; oral acyclovir 400 mg 5×/day; avoid topical steroids alone (can worsen)

1G. Neonatal HSV

• Acquired during vaginal delivery through infected birth canal
• Risk highest with primary maternal infection in 3rd trimester
• Three patterns: skin/eye/mouth (SEM), CNS, disseminated
• Disseminated neonatal HSV: mortality >80% untreated; long-term CNS complications (mental retardation, chorioretinitis, seizures)
• Treatment: Acyclovir IV 20 mg/kg every 8 hours × 21 days (CNS/disseminated) or 14 days (SEM)

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Diagnosis of HSV

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Treatment of HSV

Oral Herpes (HSV-1)

Genital Herpes (Washington Manual / CDC Guidelines)

HSV in HIV/Immunocompromised Patients

Severe/Disseminated HSV (IV Therapy)

Acyclovir Resistance

• Rare in immunocompetent; more common in immunocompromised (especially HIV)
• Mechanism: thymidine kinase mutation (most common) or DNA polymerase mutation
• Treatment: IV Foscarnet (40 mg/kg every 8 hours); cidofovir as alternative
• Always suspect if lesions not responding after 7-10 days of treatment

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PART 2: HERPES ZOSTER (VZV / Shingles)

Epidemiology

• Lifetime incidence: 10-20% of the general population
• Incidence: 3-5 per 1000 per year in general population; >10 per 1000 per year in patients >75 years
• Risk factors: increasing age, immunosuppression (HIV, lymphoma, corticosteroids, organ transplant), diabetes
• HIV-positive individuals have 15-fold higher risk than immunocompetent

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Clinical Stages and Features

• Dermatomal pain: sharp, burning, stabbing, aching; may mimic cardiac, pleural, or abdominal pathology
• Dysesthesias, allodynia, hyperalgesia in the affected dermatome
• Headache, malaise, low-grade fever

• Erythematous maculopapular rash → grouped vesicles on an erythematous base within a single dermatome, strictly unilateral, not crossing the midline
• Progression: maculopapular → vesicular (day 1-3) → pustular (day 3-4) → crusting by day 10
• Full healing in 2-4 weeks in immunocompetent
• Most common: thoracic dermatomes (50-60%); trigeminal (ophthalmic division, V1) second most common

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Special Syndromes of Herpes Zoster

Herpes Zoster Ophthalmicus (HZO)

• VZV reactivation in the ophthalmic branch (V1) of the trigeminal nerve
• Rash on forehead, eyelid, tip/side of nose (Hutchinson's sign = nasociliary branch involvement → predicts ocular complications)
• Complications: keratitis, uveitis, corneal scarring, risk of blindness
• Urgent ophthalmology referral required; IV acyclovir if significant eye involvement

Ramsay Hunt Syndrome (Herpes Zoster Oticus)

• VZV reactivation in the geniculate ganglion of the facial nerve (CN VII)
• Triad: ipsilateral facial palsy + vesicles in the external ear (pinna/ear canal/tympanic membrane) + ipsilateral hearing loss/tinnitus/vertigo
• May also involve CN VIII
• Treatment: Acyclovir (or valacyclovir) + prednisone (to reduce nerve inflammation and improve facial nerve recovery); prognosis worse than Bell's palsy

Herpes Sine Herpete

• Dermatomal pain without any rash; diagnosis confirmed by VZV PCR or serology

Disseminated Zoster

• 20 vesicles outside the primary and adjacent dermatomes

• Occurs primarily in immunocompromised patients (13-50% of cases)
• Risk of visceral involvement: pneumonitis, hepatitis, encephalitis
• IV acyclovir mandatory

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Histopathology (Tzanck Preparation)

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Diagnosis of Herpes Zoster

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Treatment of Herpes Zoster

Antiviral Therapy (Fitzpatrick's / Bradley & Daroff's, Table 165-4)

Famciclovir or valacyclovir are preferred over oral acyclovir due to better bioavailability, higher tissue drug levels, and TID (vs 5×/day) dosing. VZV is less sensitive to acyclovir than HSV.

Corticosteroids

• Prednisone 40-60 mg/day tapering over 21 days added to antiviral therapy
• Reduces severity of acute pain and speeds rash healing
• Does NOT prevent postherpetic neuralgia in randomized trials
• Indicated for Ramsay Hunt syndrome (to improve facial nerve recovery) and severe acute pain in older patients without contraindications

Topical Therapy (acute phase)

• Cool compresses, calamine lotion, cornstarch, baking soda to dry lesions
• Do NOT use occlusive ointments, topical steroids, or topical antivirals (not effective)
• Bacterial superinfection: topical or systemic antibiotics if cellulitis develops

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Postherpetic Neuralgia (PHN) - Treatment

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Prevention: Vaccination

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Quick Summary: Herpes Treatment at a Glance

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