Pharmacotherapy of Dermatologic Disorders | Module 05 Notes

Overview

Prevalence and Common Conditions

• Skin disorders are very common; ~5% of people have a skin, nail, or hair condition.

• Elderly individuals often have two or more chronic skin conditions (e.g., dermatitis, skin cancer, fungal infections).

• Common dermatologic conditions treated with topical therapy:

  • Atopic dermatitis

  • Contact dermatitis

  • Minor skin infections

  • Acne

Purposes of Topical Drug Application

1. Local Treatment – Directly treats skin disorders using topical agents (e.g., corticosteroids, antibiotics, retinoids, fluorouracil).

2. Systemic Treatment – Drugs absorbed transdermally to treat systemic conditions (e.g., clonidine for hypertension, estrogen therapy, opioids for pain).

Percutaneous Drug Absorption Considerations

• Site of application: affects drug absorption (varies by body location).

• Skin integrity: Compromised skin increases absorption and systemic effects.

• Infection presence: can alter treatment approaches (e.g., infected atopic dermatitis).

• Drug concentration & vehicle type: affect drug penetration and effectiveness.

• Absorption mechanism: Passive diffusion is the primary method of drug movement.

Skin Structure and Drug Penetration

• Epidermis (avascular, mainly keratinocytes) undergoes renewal every ~25-40 days.

• Stratum corneum (outermost layer) acts as the major barrier to drug penetration.

• Drug penetration occurs via:

  • Transappendageal route (minor pathway) – through sweat ducts, hair follicles.

  • Transepidermal routes:

    • Intracellular lipid route – Major route, drugs diffuse between cells.

    • Transcellular route – Less common, drugs pass directly through cells.

Drug Absorption Terms

• Penetration – Entry of drug into the stratum corneum.

• Permeation – Drug diffusion through skin layers.

• Resorption – Drug uptake into systemic circulation.

• Reservoir Effect – Some drugs (e.g., fentanyl patch) remain in the skin and continue absorption after removal.

General Principles

The effectiveness of a topical drug depends on both the drug’s inherent potency and its ability to penetrate the skin, which is influenced by drug properties, formulation (vehicle), and skin conditions.

1. Drug Properties Affecting Absorption

• Molecular size: Smaller molecules (<500 Daltons) penetrate better.

• Ionization: Un-ionized drugs diffuse more easily; pH impacts ionization balance.

• Lipophilicity: The drug must balance lipid and water solubility for optimal skin penetration.

• pH of Skin:

  • Normal acidic pH (4-5) favors acidic drugs with lower pKa values.

  • Diseased or alkaline skin favors basic drugs.

• Therapeutic considerations: Ideal topical drugs should be potent at low doses (<20 mg/day), have short half-lives, and not cause irritation or immune reactions.

2. Role of the Vehicle (Formulation)

• The vehicle does not significantly penetrate the skin but affects drug absorption by:

  • Modulating drug release from the formulation.

  • Altering skin barrier properties (e.g., hydration).

  • Increasing drug solubility in the stratum corneum.

• Formulation can impact a drug’s potency, as seen with topical corticosteroids:

  • Even at the same drug concentration, different formulations (e.g., ointments, creams, lotions) lead to different potencies.

  • Ointments are generally more potent than creams, which are more potent than lotions.

  • Different salts of the same drug (e.g., hydrocortisone acetate vs. hydrocortisone butyrate) also differ in potency due to lipid solubility variations.

3. Comparison of Common Topical Formulations

4. Absorption and Bioavailability of Topical Drugs

• Low absorption does not mean low efficacy. Some highly potent drugs (e.g., fluocinolone acetonide) have poor absorption but still work well at low doses.

• Absorption rates vary by drug:

  • Hydrocortisone: <2% absorbed in 24 hours.

  • Nicotine (transdermal patch): 75-90% bioavailability.

• Peak absorption occurs 12-24 hours post-application.

• Concentration-driven absorption: Higher drug concentration in the formulation increases absorption due to passive diffusion.

5. Frequency of Application & Occlusion Effects

• Once-daily application of topical steroids is as effective as multiple applications.

  • The skin acts as a reservoir, allowing prolonged drug action.

  • Less frequent application improves patient adherence.

• Occlusion (e.g., saran wrap, occlusive dressings):

  • Increases skin hydration and temperature, enhancing drug penetration.

  • More hydration leads to better absorption.

• Vehicle Types:

  • Ointments provide occlusion, enhance absorption, but may cause maceration in oozing lesions.

  • Creams are useful for inflammatory lesions and intertriginous areas but may cause irritation due to preservatives.

  • Lotions are useful for application on hairy areas and drying oozing lesions but are less potent than creams or ointments.

  • Gels can be very potent and are useful for wet lesions like poison ivy but should be used cautiously under specialist guidance.

• Drug Absorption:

  • Absorption can be influenced by factors like the vehicle, skin hydration, occlusion, and the thickness of the stratum corneum.

  • For example, occlusion enhances drug absorption significantly but may also increase the risk of side effects like skin atrophy or systemic toxicity.

  • The site of application plays a huge role: thinner skin (like eyelids and scrotum) facilitates higher absorption than thicker skin (like the soles of feet).

• Age Factors:

  • Elderly skin tends to be thinner and drier, which can alter drug absorption.

  • Children, especially infants and newborns, have thinner skin and higher absorption rates. Newborns, in particular, have a higher body surface area to body weight ratio, increasing the risk for systemic toxicity.

• Skin Damage: Any damage to the skin barrier, such as from disease or trauma, can increase absorption. For example, in conditions like atopic dermatitis or severe psoriasis, the absorption of topical medications can be much higher than in healthy skin.

• Local and Systemic Side Effects:

  • Local effects can include irritation, allergic reactions, atrophy, acne, and telangiectasia.

  • Systemic effects may range from CNS toxicity to hormonal imbalances, and the metabolism of the drug can be influenced by skin enzymes.

Topical Drug Preparations and Absorption:

1. Vehicles and Their Effects:

   • Ointments: Provide occlusion, enhancing drug absorption but can cause maceration in oozing lesions. They are more potent but not ideal for areas where moisture needs to be absorbed.

   • Creams: Useful for acute inflammatory lesions, especially those that are exudative or oozing, due to their drying effects. They’re effective in intertriginous areas but may cause irritation due to preservatives.

   • Lotions: Often alcohol-based and can dry oozing lesions more effectively than creams. They are useful for application to hairy areas but are less potent and effective than ointments or creams.

   • Gels: Very potent, especially for wet lesions like those from poison ivy. They tend to dry quickly and don’t leave residue, but they are highly potent and should be used with caution under specialist guidance, as they may cause significant absorption.

2. Absorption and Bioavailability:

   • Topical drugs are absorbed at low rates, with less than 2% of some corticosteroids (e.g., hydrocortisone) absorbed after a single application. However, absorption can be enhanced with higher concentrations of the drug or specific vehicles.

   • Occlusion: Enhances hydration and skin temperature, promoting absorption. It can increase drug absorption by 10 to 100 times, leading to faster onset and higher efficacy. However, occlusion may also increase the risk of side effects like skin atrophy or systemic side effects (e.g., suppression of the hypothalamic-pituitary-adrenal axis).

   • The stratum corneum's thickness and integrity affect absorption. Thinner skin areas like the eyelids and scrotum have much higher drug penetration, while thicker areas like the soles of feet have lower absorption.

3. Factors Influencing Absorption:

   • Age:

     • Elderly skin tends to be thinner, drier, and less lipid-rich, potentially reducing the absorption of some drugs while increasing the absorption of lipophilic drugs. However, aged skin may also be more friable, leading to easier penetration if damaged.

     • In newborns and infants, skin is thinner and more permeable, leading to increased absorption rates, particularly in premature infants. Their higher body surface area-to-weight ratio also increases the risk of systemic toxicity from topical medications.

   • Skin Damage: Conditions that compromise the skin’s barrier, like atopic dermatitis or severe psoriasis, can significantly increase drug absorption, leading to potentially higher systemic effects.

4. Efficacy of Topical Drugs:

   • The efficacy of topical medications depends on the drug’s inherent potency, its ability to penetrate the skin, and the concentration in the product. A drug’s efficacy can be independent of absorption; even poorly absorbed drugs can be effective due to their potency.

   • Frequency of Application: Multiple daily applications generally do not enhance the efficacy of topical drugs. In fact, once-daily applications often work just as well, increasing patient adherence and minimizing adverse effects.

   • Local and Systemic Side Effects:

     • Local Effects: These can include irritation, allergic reactions (even to corticosteroids), atrophy, acne, telangiectasis, and more. These effects are often due to the excipients or emulsifiers in the product rather than the drug itself.

     • Systemic Effects: These can range from CNS toxicity to electrolyte imbalances, endocrine disruptors, teratogenicity, and even carcinogenicity with prolonged use.

5. Skin Enzymes and Metabolism:

   • The skin is metabolically active, containing enzymes that can affect the absorption and effectiveness of topical drugs. However, the overall impact of these enzymes is usually modest (about 2-5% of the applied drug). Some drug transporters present in the skin can also influence absorption.

Key Takeaways:

• The vehicle in which a drug is delivered plays a crucial role in absorption, and occlusion can dramatically increase drug effectiveness.

• Skin thickness and damage, age, and hydration significantly influence how drugs are absorbed.

• Local side effects from topical drugs are common, and systemic toxicity can occur if absorption is higher than expected, particularly in infants or those with compromised skin.

• Ointments provide the highest potency and hydration but may be too occlusive for certain areas.

• Different formulations of the same drug can have varying potencies, even at the same concentration.

• Absorption is slow, but high inherent potency can still lead to strong therapeutic effects.

• Once-daily application is often sufficient for effectiveness, improving adherence.

• Topical drugs are designed for local skin treatment, while transdermal drugs are absorbed systemically.

• Stratum corneum is the primary barrier to drug penetration.

• Percutaneous absorption occurs primarily via intracellular lipid diffusion rather than transcellular routes.

Topical Corticosteroids

Mechanism of Action

• Glucocorticoid Receptor: Corticosteroids bind to intracellular glucocorticoid receptors, regulating gene transcription and protein synthesis in target tissues.

• Effects: 10-20% of expressed genes are regulated, leading to wide-ranging effects.

Anti-inflammatory Effects

• Arachidonic Acid Cascade: Inhibits prostaglandin production and proinflammatory cytokines (e.g., IL-1).

• Lysosomal Stabilization: Prevents enzyme release from damaged cells, reducing inflammation.

Immunosuppressive Effects

• Lymphocyte/Monocyte Apoptosis: Inhibits migration of leukocytes to sites of inflammation.

• Phagocytosis Inhibition: Reduces macrophage and lymphocyte response to antigens, impairing cellular immunity.

Key Dermatological Effects

• Vasoconstriction: Reduces capillary permeability, leading to skin blanching, and is used to measure potency.

• Antimitotic: Decreases epidermal cell mitosis, contributing to the effectiveness in conditions like psoriasis.

Steroid Potency Classification

• Group 1: Most potent (dermatologist use)

• Group 7: Least potent (appropriate for nurse practitioners)

General Guidelines for Use

• Choose the Lowest Potency: Use the least potent steroid that clears an eruption quickly.

• Duration: Limit high-potency steroids (Group 1-3) to 2-3 weeks. For moderate/low-potency (Group 4-7), treatment can last up to 6 weeks with gradual tapering.

• Children/Elderly: Avoid high-potency steroids due to systemic toxicity risks.

De-escalation Strategy

• Once inflammation is controlled, reduce steroid potency or switch to a non-steroid regimen to maintain healthy skin.

Important Considerations

• Occlusion: Can enhance drug absorption but also increase side effects.

• Tachyphylaxis: Reduced response after several doses. Manage by taking breaks from the drug.

Adverse Effects

• Local:

  • Skin Atrophy: Thinning, wrinkling, and hypopigmentation (permanent).

  • Striae (Stretch Marks): Irreversible scars.

  • Steroid Acne/Rosacea: Common in long-term use.

• Systemic:

  • Cushing’s Syndrome: Fat accumulation, hypertension, hyperglycemia.

  • Adrenal Insufficiency: Can lead to adrenal crisis, especially in children (e.g., diaper dermatitis).

Key Takeaway: Always monitor for side effects, and aim for the lowest effective potency. Use higher-potency steroids with caution, especially in sensitive areas (e.g., face, genitalia).

Eczematous Dermatitis

Dermatitis: Inflammation of the skin, without specifying the cause.
Eczema: A type of inflammatory skin reaction that includes conditions like atopic dermatitis, contact dermatitis, seborrheic dermatitis, etc.

Stages of Eczematous Inflammation

• Acute: Red, wet, and itchy with papules, vesicles, and bullae (e.g., poison ivy, fungal infections).

• Subacute: Erythema, scaling, dryness, and mild to moderate pruritus.

• Chronic: Thickened, lichenified skin with ongoing pruritus, often due to habitual scratching.

Complications

• Bacterial Infections: Commonly caused by Staphylococcus aureus or Streptococcus.

• Viral Infections: Herpes simplex, molluscum contagiosum.

• Psychological/Physical Impact: Discomfort, limitation, and distress.

Atopic Dermatitis (AD)

• Definition: A chronic, pruritic, inflammatory skin disease often linked to allergies (e.g., asthma, food allergies). It occurs in children but also affects adults.

• Prevalence: Affects 20-30% of children and 7-10% of adults.

• Systemic Nature: Increasingly recognized as a systemic condition with immune and barrier dysfunction.

Pathogenesis

• Genetic & Environmental Factors: Atopic dermatitis results from a complex interaction between genetic predisposition, environmental triggers, and immune system abnormalities.

• Immune Dysregulation: Type 2 immune dysfunction and epidermal barrier impairment are key features.

• Microbiome: Disruptions in skin bacteria, particularly overgrowth of Staphylococcus aureus, contribute to AD severity.

Types of Atopic Dermatitis

• Infantile: Typically resolves by age 2-3, presenting with erythema, vesicles, and oozing.

• Childhood: Chronic, with lichenification and involvement of flexural areas like wrists and ankles.

• Adult: More widespread, often with thickened, dry lesions and exacerbations of pruritus.

Contact Dermatitis

• Irritant Contact Dermatitis: Caused by exposure to substances like detergents or solvents, damaging the skin barrier.

• Allergic Contact Dermatitis: Caused by allergens (e.g., poison ivy, nickel, latex), leading to a delayed hypersensitivity reaction.

Clinical Presentation:

• Pruritic lesions, often with sharp, demarcated edges.

• Acute or chronic forms, typically asymmetric and localized to areas of contact.

Eczematous Dermatitis Treatment

1. Assessing the Rash:
To determine the extent of the rash, we use the Rule of Nines to estimate the total body surface area (TBSA) involved. For smaller or mixed burns, the palm of the hand method can be used—1 palm equates to about 1% of TBSA.

2. Treatment Goals:
The primary treatment objectives are:

• Eliminate Inflammation

• Prevent or Treat Infection

• Restore the Skin Barrier with emollients and moisturizers

• Reduce Self-inflicted Skin Damage (e.g., from scratching)

• Control Exacerbating Factors (stress, allergens, etc.)

For poison ivy/oak/sumac, the focus shifts to preventing oozing and crusting, as the allergen can spread through the fluid.

3. Acute Inflammation Management:

• Cold Compresses for soothing

• Topical Steroids (oral or intramuscular, depending on severity)

• Antibiotics if infection is present

• Antihistamines, though less effective for pruritus, may be used to help with sleep.

4. Wet Compresses:

• Used for acute flares to relieve irritation, cool the skin, and assist with drying weeping lesions.

• Aluminum acetate (Burrow's solution) can be added to reduce protein buildup and suppress oozing.

5. Chronic & Subacute Inflammation:

• Hydration and Lubrication are key for healing.

• Topical Steroids (mild to moderate)

• Sedating Antihistamines may be considered for night-time relief.

6. Atopic Dermatitis & Contact Dermatitis:

• Initial Treatment: Start with emollients and topical corticosteroids.

• Hydration is critical, especially for subacute and chronic stages.

• Use mild, non-soap cleansers (e.g., Cetaphil) to prevent skin drying.

7. Severe Cases (Moderate to Severe Atopic Dermatitis):

• Topical Calcineurin Inhibitors (TCIs) and Systemic Treatments (methotrexate, biologics, JAK inhibitors) may be necessary if topical treatments are ineffective.

• Proactive Treatment: To reduce flare-ups, apply topical steroids or TCIs twice weekly for two consecutive days.

8. Evaluating Treatment Response:

• There are no specific biomarkers for tracking treatment success, but key indicators of treatment failure include:

  • Insufficient improvement

  • Flare-ups despite treatment

  • Unresolved impact on quality of life

  • Adverse side effects from medication

9. Long-Term Care:

• Patients with severe dermatitis may require long-term topical steroid use.

• If treatment isn’t working, consider a dermatology referral for a comprehensive reassessment.

10. Topical Steroids Overview:

• Mild to Moderate: Can be used by nurse practitioners for flare management.

• Potent Steroids: Typically prescribed by dermatologists for more severe cases.

• Safety Considerations: Use the least potent steroid necessary, and avoid long-term systemic steroid use due to potential side effects.

Non-Corticosteroid Therapies for Eczematous Dermatitis

Topical Calcineurin Inhibitors (TCIs)

• Pimecrolimus (cream) and Tacrolimus (ointment) are alternatives to topical steroids.

• Benefits: No skin atrophy risk, suitable for sensitive areas like the face, and effective for both short-term flare-ups and long-term maintenance.

• Efficacy:

  • Pimecrolimus: Effective for mild atopic dermatitis (comparable to low-potency steroids).

  • Tacrolimus: More effective for moderate to severe cases (comparable to moderately potent steroids).

• Mechanism: Inhibit T-cell activation and cytokine production by blocking calcineurin, reducing inflammation.

• Safety: Long-term use carries a theoretical cancer risk (black box warning), but clinical studies show minimal evidence of lymphoma or skin cancer. Risk is minimal with topical use compared to systemic treatments.

• FDA Recommendations: Use as second-line therapy for patients who don't respond to steroids, with caution in children under 2 and immunocompromised patients.

Crisaborole (PDE4 Inhibitor)

• Mechanism: Inhibits PDE4, increasing cyclic AMP and reducing inflammation by promoting anti-inflammatory mediators and regulating T-cell activity.

• Usage: Approved for mild to moderate atopic dermatitis in adults and children (3 months+), applied twice daily.

• Safety: Well-tolerated, though may cause mild site pain or hypersensitivity. Safe during pregnancy (no significant developmental effects observed in animal studies).

Dupilumab (IL-4/IL-13 Inhibitor)

• Mechanism: Blocks IL-4 and IL-13, key cytokines in atopic dermatitis inflammation.

• Usage: Indicated for moderate to severe cases not controlled by topical steroids. Also used in asthma and chronic rhinosinusitis.

• Efficacy: Significant improvement in severity and itch within the first week.

• Safety: Common side effects include injection site reactions and conjunctivitis. Pregnancy and lactation data are limited, but no significant risks identified in case studies.

JAK Inhibitors (Abrocitinib, Upadacitinib, Ruxolitinib)

• Mechanism: Target Janus kinases (JAKs) involved in the inflammatory response, reducing cytokine production.

• Usage: Typically reserved for refractory cases, used when other treatments fail.

• Safety: Can cause side effects like infection risk and blood abnormalities, and are generally recommended for patients aged 12+.

Referral to a Specialist
Consider referral for:

• Diagnostic uncertainty or poor treatment compliance.

• Treatment failure with topical therapy or need for more potent options.

• Involvement of sensitive areas or frequent infections.

• Disruptions in quality of life, including excessive itching or psychological distress.

These non-steroidal treatments offer alternative approaches to managing atopic dermatitis, especially for patients who need steroid-sparing options.

Topical Antibiotics

Topical Antibiotics for Minor Skin Infections

This section focuses on the treatment of minor skin infections, also known as pyodermas, using topical antibiotics. Common infections include:

• Impetigo

• Folliculitis

• Furuncles

• Carbuncles

Etiologic Agents:

• Staphylococcus aureus (most common)

• Group A beta-hemolytic streptococcus

• Pseudomonas aeruginosa (in Folliculitis)

• Fungal causes (Candida, Pityrosporum ovale)

Topical Antibiotics:

• Primary Uses:

  • Treat superficial infections

  • Prevent infections (e.g., pre-surgical use)

  • Manage acne and non-infectious skin conditions (due to anti-inflammatory effects)

• Important Considerations:

  • Antibiotic selection depends on diagnosis and culture results

  • Empiric therapy often based on common pathogens (Staph aureus, Strep)

  • Local resistance patterns are important (antibiograms)

Impetigo:

• Description: A contagious skin infection affecting the epidermis and dermis, often with honey-colored crusting.

• Causes: Mostly Staphylococcus aureus and sometimes Group A beta-hemolytic streptococcus.

• Forms:

  • Nonbullous: Smaller lesions

  • Bullous: Larger blisters (more concerning in infants/children due to risk of fluid loss)

• Symptoms: Mild itching, soreness, local symptoms, rare systemic signs (fever, lymphadenopathy)

Treatment:

• Topical Antibiotics: First-line for uncomplicated, localized infections (less than 10 lesions, less than 100 cm² area, or <2% body surface area).

  • Advantages:

    • Targeted, high concentrations at infection site

    • Fewer systemic side effects

    • Better patient acceptance (especially in children)

  • Systemic Antibiotics: Indicated for more extensive or severe infections, or if topical therapy fails.

Common Topical Antibiotics:

• Bacitracin:

  • Mainly used for prophylaxis against gram-positive organisms.

  • Mechanism: Inhibits bacterial cell wall synthesis.

• Mupirocin:

  • Effective against Staphylococcus aureus (including MRSA) and Group A streptococcus.

  • Used for Impetigo and nasal decolonization of Staph aureus.

  • Fewer systemic side effects than oral antibiotics.

• Retapamulin:

  • Active against Staph aureus (methicillin-susceptible) and Group A streptococcus.

  • Not effective against MRSA.

• Neomycin & Gentamicin:

  • Aminoglycosides used for gram-negative infections.

  • Neomycin: Typically used for prophylaxis, can cause allergic contact dermatitis.

  • Gentamicin: Risk of systemic toxicity with large surface area applications.

• Polymyxin B:

  • Used for prophylaxis against gram-negative organisms.

  • Often combined with other antibiotics.

Topical Antifungals

Overview: There are various antifungal treatments available to manage minor skin infections, both topical and systemic. The main types of topical antifungal agents are the azoles and allylamines.

1. Azoles:

• Includes drugs like clotrimazole, econazole, miconazole, ketoconazole, oxyconazole, sulconazole, and sertaconazole (some available over the counter).

• Primarily effective against yeast but also effective against dermatophytes.

• Mechanism: Block the conversion of lanosterol to ergosterol, weakening the fungal cell wall and leading to cell death.

2. Allylamines:

• Effective against dermatophytes but less so for yeasts.

• Mechanism: Inhibit squalene epoxidase, another enzyme involved in ergosterol synthesis, impairing the fungal cell wall.

Adverse Effects:

• Azoles and allylamines may cause mild local reactions like stinging, itching, or erythema.

Other Topical Agents:

• Nystatin: For cutaneous or mucosal Candida infections. Can be used for oral thrush or perianal/vulvar infections.

• Tolnaftate: Effective for dermatophytes, not Candida. Used in creams, solutions, and powders, applied twice daily.

• Ciclopirox: Broad-spectrum antifungal agent effective against dermatophytes, Candida, and pityrosporum, although it has low cure rates.

• Amphotericin B: Primarily for Candida but ineffective for dermatophytes.

Topical Steroids:

• May be combined with antifungal agents but can suppress the local immune response, potentially worsening the infection.

Systemic Treatments:

1. Griseofulvin:

• Fungistatic agent that prevents fungal cell division by disrupting the mitotic spindle.

• Commonly used for tinea capitis (scalp fungal infection), typically requiring 4-6 weeks of therapy.

• Side effects: Nausea, photosensitivity, liver toxicity, and it interacts with contraceptives.

2. Terbinafine:

• Broad-spectrum antifungal: useful for tinea capitis, often producing a faster and better mycological response than griseofulvin.

• Side effects: Liver enzyme elevations, gastrointestinal issues, and rare bone marrow suppression.

3. Prescription Azoles:

• Itraconazole, Fluconazole, and Ketoconazole are used systemically for tinea infections, with itraconazole being FDA-approved for tinea capitis.

• Side effects: Hepatotoxicity (notably with ketoconazole), gastrointestinal complaints, and more.

Special Cases and Considerations:

Tinea Capitis:

• Always requires systemic therapy as topical treatments cannot penetrate the hair follicle.

Other Conditions Needing Systemic Therapy:

• Hyperkeratotic infections (palms/soles), extensive or disabling infections, and chronic recalcitrant infections may benefit from oral treatment.

Asymptomatic Carriers:

• Individuals who harbor fungal organisms but show no symptoms can still transmit infection.

• Treatment for carriers is controversial, but some experts recommend antifungal shampoo or systemic therapy based on the severity of fungal growth.

Monitoring:

• Regular follow-up is important, especially in cases of griseofulvin resistance, to assess treatment efficacy and adjust accordingly.

Pathophysiology of Acne Vulgaris

• Acne vulgaris: Chronic, inflammatory disorder of the pilosebaceous follicles.

• Prevalence: Affects 80% of people aged 12-25; can persist beyond 25 in 3% of men and 12% of women.

• Psychological impact: Acne causes scarring, hyperpigmentation, and affects self-esteem.

• Costs: Over $1 billion annually in medical costs, with over-the-counter treatments contributing to $1 million in expenditures each year.

Contributing Factors:

• Sebaceous Gland Hyperplasia: Increased oil production triggered by hormonal changes (especially androgens during puberty).

• Altered Follicular Growth: Abnormal keratinization leads to clogged follicles.

• Bacterial Colonization: Cutibacterium acnes thrive in excess oil, causing inflammation.

• Inflammation: Results in papules, pustules, and nodules (inflammatory lesions).

Types of Lesions:

• Non-inflammatory lesions:

  • Whitehead (closed comedo): Keratin and sebum buildup within a closed follicle.

  • Blackhead (open comedo): Similar to a whitehead but with oxidized melanin exposed to air.

• Inflammatory lesions:

  • Papule: Red, inflamed lesion without follicle rupture.

  • Pustule: Inflamed lesion with pus due to follicular rupture.

  • Nodule: Larger, deeper lesion often leading to severe scarring.

Acne Severity:

• Mild acne: Few non-inflammatory lesions, minimal inflammation.

• Moderate acne: More significant inflammation, but no nodules.

• Severe acne: Numerous inflammatory lesions, possibly nodules or cystic lesions.

Severe Forms:

• Acne Conglobata: Severe nodulocystic acne with abscesses and draining sinus tracts.

• Acne Fulminans: Sudden systemic inflammation, fever, joint pain, and severe skin lesions.

Treatment Approach:

• Combination therapy is key, targeting multiple factors at once.

Drug Therapy for Acne Vulgaris

Benzoyl Peroxide:

• Action:

  • Antibacterial agent killing Cutibacterium acnes via free oxygen radicals.

  • Mild comedolytic, keratolytic, and anti-inflammatory effects.

  • Primary action is antibacterial.

• Effectiveness:

  • Recommended as monotherapy for mild acne.

  • Enhances results when combined with topical or oral treatments for mild-to-severe acne.

  • Improves scar appearance over six months when used with a topical retinoid.

• Resistance:

  • No bacterial resistance reported in Cutibacterium acnes.

  • Reduces bacterial resistance when paired with antibiotics.

• Application:

  • Penetrates the skin, metabolized into benzoic acid with minimal systemic absorption (<5%).

  • Available as washes, foams, creams, gels (leave-on or wash-off).

• Side Effects:

  • Irritation, bleaching of fabrics, photosensitivity.

  • Rare contact dermatitis.

  • Lower concentrations (2.5-5%) recommended for sensitive skin.

• Usage:

  • Start with low concentrations once daily, increasing frequency and strength gradually.

Azelaic Acid:

• Indications:

  • Inflammatory acne, hyperpigmentation, acne rosacea.

• Action:

  • Antibacterial, anti-comedonal, and keratolytic effects.

  • Inhibits conversion of testosterone to dihydrotestosterone, potentially reducing acne.

• Tolerance:

  • Well-tolerated with mild side effects (pruritus, burning, erythema in 1-5%).

  • Ideal for patients with sensitive skin who can't tolerate retinoids.

• Pregnancy Category: B.

Topical Antibiotics:

• Clindamycin (1%):

  • Preferred due to lower resistance rates.

  • Works by inhibiting bacterial protein synthesis.

  • Can cause rare Clostridium difficile-related diarrhea.

• Erythromycin (2%):

  • Less effective due to resistance in Cutibacterium acnes.

  • Available in various forms (cream, gel, lotion).

• Usage:

  • Best used with benzoyl peroxide to reduce bacterial resistance.

  • Avoid monotherapy for prolonged periods to prevent resistance.

Dapsone:

• Indications:

  • 5% gel for moderate acne, often in combination with retinoids.

• Precaution:

  • Topical use does not cause clinically relevant hemolysis in G6PD deficiency.

  • Can cause temporary orange discoloration when combined with benzoyl peroxide.

Systemic Antibiotics:

• Tetracyclines (e.g., doxycycline, minocycline):

  • Used for moderate-to-severe acne.

  • Inhibit bacterial protein synthesis and have anti-inflammatory effects.

  • Side effects: photosensitivity, dizziness, tinnitus, autoimmune reactions (minocycline).

• Alternative Antibiotics:

  • Macrolides (e.g., erythromycin, azithromycin) for patients unable to take tetracyclines.

  • Trimethoprim/Sulfamethoxazole as second-line therapy for pregnant patients or those allergic to other antibiotics.

• Resistance:

  • Resistance to Cutibacterium acnes is growing, particularly with macrolides.

• Usage:

  • Systemic antibiotics should be discontinued after 3-4 months, maintaining control with topical treatments.

Acne Treatment Recommendations:

• Mild Acne:

  • Initial treatment: benzoyl peroxide or topical retinoid.

• Inflammatory Acne:

  • Combination therapy with benzoyl peroxide + retinoids or antibiotics.

• Moderate Acne:

  • Add oral antibiotics (e.g., tetracyclines) if topical treatments fail.

  • Consider oral contraceptives or spironolactone for hormonal acne.

• Severe Acne:

  • Isotretinoin or a 2-3 drug regimen (including oral antibiotics).

• Referral to Dermatology:

  • Recommended for moderate-to-severe acne, scarring, or hormonal acne.

Combination Therapy:

• Best Practice:

  • Combination of topical antibiotics with retinoids or benzoyl peroxide.

  • More effective than monotherapy and prevents resistance.