L-23 Dermatologic Treatments: History and Evolution

Dermatologic Systemic & Surgical Treatments & Therapeutics

• Stanley Skopit, DO, MSE, FAOCD, FAAD is a Clinical Professor of Dermatology, NSU-KPCOM
• Additionally, Skopit is a Clinical Associate Professor, Affiliated, Dermatology, NSU-MD
• Serves as the Program Director, ACGME Dermatology Residency Training Program
• Skopit is the Chairman, Department of Dermatology at Larkin Community Hospital

Historical Context

• Early dermatological treatments included mercury for syphilis, and arsenauro and mercauro as blood builders
• Unguentine was used as an antiseptic for inflammation with a formula modified from Sir Astley Cooper
• Freligh's Tonic claimed to be a panacea for numerous ailments and skin eruptions
• Opium was once used as a treatment for asthma

Evolution of Treatments

• In the late 19th to early 20th century, treatments were simple: "If it's wet, dry it! If it's dry, wet it!"
• Modern (21st Century) dermatological treatments are advancing rapidly, with laser therapy being a key modality

Cosmetics & Skin Care

• The total global skin care and beauty industry spending is a large market
• $483 Billion was spent in 2020
• $716 Billion is projected for 2025
• $799.10 Billion is projected by 2030
• 51% of sales in the U.S. were purchased online in 2024

Systemic Therapy Overview

• Systemic glucocorticoids
• Sulfones
• Aminoquinolines
• Cytotoxic & antimetabolic agents
• Retinoids
• Antihistamines
• Antibiotics
• Antiviral drugs
• Antifungal agents
• Immunosuppressive & immunomodulatory agents
• Thalidomide
• Therapeutic photomedicine: phototherapy
• Photochemotherapy & photodynamic therapy
• Plasmaphoresis
• Hair regrowth

Systemic Glucocorticoids

• Properties include immunosuppression and anti-inflammatory effects.
• Used to treat blistering diseases (bullous pemphigus, bullous pemphigoid, epidermolysis bullosa, herpes gestationis, erythema multiforme, toxic epidermal necrolysis)
• Useful for connective tissue diseases (dermatomyositis, SLE, eosinophilic faciitis)
• Also treats vasculitis, sarcoidosis, leprosy, capillary hemangiomas, panniculitis, urticaria & angioedema, and severe dermatitis
• Complications are avascular necrosis, atherosclerosis, osteoporosis, suppression of the hypothalmic-pituitary axis, drug interactions, concerns during pregnancy & lactation, and immunologic side effects

Sulfones

• Properties include anti-inflammatory effects
• Dapsone is the primary drug.
• Used to treat Dermatitis Herpetiformis (DH) and Erythema Elavatum Diutinum (EED)

Aminoquinolines

• Properties include immunological effects
• Drugs are antimalarials: chloroquine, hydroxychloroquine (Plaquenil®), and quinacrine
• Used for Lupus Erythematosus (LE), Polymorphous Light Eruption (PLE), and Porphyria Cutanea Tarda (PCT)

Cytotoxic & Antimetabolic Agents

• Antimetabolic agents include Methotrexate (for cancer therapy, psoriasis, Reiter’s Syndrome, Sarcoidosis), Azathioprine, Thioguanine, and Hydroxyurea
• Alkylating agents include Cyclophosphamide (for autoimmune disease), Chlorambucil, and Anthracyclines
• Hedgehog Signaling Pathway Inhibitor: can treat advanced metastatic BCC with Erivedge -Vismodegib, taken 150mg QD and Odomzo - Sonidegib, taken 200mg QD
• Monoclonal Ab: These drugs belong to a class of drugs that binds to programmed death receptor-1, which blocks the PD-1/PD-L1 pathway for advanced treatment of SCC; Libtayo (Cemiplimab), administered via IV

Oral Retinoids

• Accutane (Isotretinoin) treats acne
• Soriatane (Acitretin) treats psoriasis
• Tegison (Etretinate) treats cutaneous disorders of cornification, including Darier's Disease, Pityriasis Rubra Pilaris (PRP), and Grover's Disease

Antihistamines

• Indications include pruritus, urticaria, & angioedema
• 1st Generation H-1 (Traditional, Classic): Hydroxyzine (Atarax), Meclizine (Antivert)
• 2nd Generation H-1 (Low Sedation): Terfenadine (Seldane®), Astemizole (Hismanal®), Cetirizine (Zyrtec), Loratadine (Claritin®)
• 3rd Generation H-1 Antagonists (H1 blockers block action of histamine at the H1 receptor =↓ allergies): Desloratadine (Clarinex®), Fexofenadine (Allegra®), Levocetirizine (Xyzal®)
• H-2 Type Receptor Antagonists (Reduce the amount of acid produced by cells in the stomach lining): Cimetidine (Tagamet®), Ranitidine (Zantac®), Famotidine (Mylanta, Pepcid®), Nizatidine (Axid®)
• Tricyclic Antidepressants like Doxepin can be a therapeutic agent with antihistamine activity

Oral Antibiotic Overview

• Penicillins: Penicillin V, Dicloxacillin, Amoxicillin
• Cephalosporins: Cephalexin, Cephradine
• Tetracyclines: Doxycycline, Minocycline, Tetracycline
• Macrolides: Azithromycin, Clarithromycin, Erythromycin
• Fluoroquinolones: Ciprofloxacin, Oflaxacin, Levofloxacin
• Clindamycin
• Trimethoprim-sulfamethoxazole

Oral Antiviral Drugs

• Treatment for HSV & HVZ viral infections: Acyclovir (Zovirax®), Valacyclovir (Valtrex®), Famciclovir (Famvir®)
• Treatment for CMV infections: Ganciclovir (Guanine®), Foscarnet (Foscavir®), Cidofovir (Vistide®)
• Treatment for HIV infections: Reverse Transcriptase Inhibitors, Protease Inhibitors, and Antiretroviral Drugs.
• Interferons are cytokines that are antiviral, immunomodulating & antiproliferative

Oral AntiFungal Agents

• Terbinafine (Lamisil®) – Allylamine- antimycotic
• Triazoles – antimycotic: Itraconazole (Sporanox®), Fluconazole (Diflucan®)
• Ketoconazole (Nizoral®) – Imidazole - fungistatic
• Griseofulvin – narrow spectrum antimycotic; (penicillin sensitivity in 10% of patients): Microsize & Ultramicrozise

Immunosuppressive & Immunomodulatory Drugs

• Cyclosporine (Neoral®) – Calcineurin Inhibitor (Oral)
• Enbrel® (Etanercept) - Anti-TNF (SubQ)
• Amevive ® (Alefacept) – Fusion protein (Taken off Market)
• Raptiva® (Efalizumab)- (Taken off the market)
• Remicade® (Infliximab) – Anti-TNF (IV Infusion)
• Humira® (Adalimumab) – Anti-TNF (SubQ)
• Stelera (Ustekinumab)- IL-23 & IL-12 Inhibitor (SubQ)
• Cosentyx (Secukinumab) – IL 17A antagonist (SubQ) for moderate to severe plaque psoriasis
• Otezla® (apremilast) - phosphodiesterase 4 Inhibitor (Oral)
• Taltz® (Ixekizumab) – IL -17A inhibitor (SubQ)
• Tremfya® (Guselkumab) – IL-23 Blocker(SubQ) for moderate to severe psoriasis
• Dupixent®(Dupilumab) – IL- 4 & IL-13 Blocker (SubQ) for uncontrolled moderate to severe eczema; fully human mAb directed toward IL-4R∝
• Adbry® (tralokinumab) – IL 13 Inhibitor (SubQ) – for atopic Dermatitis
• Nemolizumab – humanized monoclonal Ab agent against IL-31 receptor A for Atopic Dermatitis in Dogs
• Skyrizi® (risankizumab-rzaa) – IL-23 antagonist (SubQ) for moderate to severe plaque psoriasis 4x/yr
• Siliq® (Brodalumab) – IL -17 receptor blocker (SubQ) for moderate to severe plaque psoriasis – 1 injqwkx3 doses then q2wks

JAK Inhibitors

• These are Janus Kinase Inhibitors and a treatment for inflammatory diseases(TYK1 & TYK2 Inhibitors)
• Cibinqo® (Abrocitinib) 100mg tab QD – moderate to severe eczema
• Rinvoq® (upadacitinib) 15-30mg tablets QD – moderate to severe atopic dermatitis
• Olumiant® (Baricitinib) 2-4mg tablets QD – disrupts cytokine & growth factor signaling pathways in alopecia areata
• Sotyktu® (Deucravacitinib) 6mg tablet QD – tablet 9 tyrosine kinase 2 inhibitor) – treatment of moderate-to-severe plaque psoriasis

Thalidomide

• Treats Erythema Nodosum Leprosum
• Treats HIV Infection
• Treats Microsporidosis
• Treats Aphthous Ulcers in AIDS
• Treats Kaposi's Sarcoma
• Treats Aphthosis & Behcet's Disease
• Treats Lupus Erythematosus
• Treats Chronic Graft-vs-Host Disease
• Treats Langerhans Cell Histiocytosis
• Treats Actinic Prurigo
• Treats Bullous Pemphigoid
• Treats Erythema Multiforme
• Treats Jessner-Kanof Disease
• Treats Palmoplantar pustulosis
• Treats Postherpetic Neuralgia
• Treats Prurigo Nodularis
• Treats Sarcoidosis
• Treats Pyoderma Gangrenosum
• Treats Uremic Pruritus
• Treats Weber-Christian Disease

Phototherapy

• Phototherapy inhibits cell proliferation
• Psoriasis can be treated via UVB
• Atopic Dermatitis can be treated via High-Dose UVA
• Polymorphous Light Eruption can be treated via PUVA or UVB
• Urticaria Pigmentosa can be treated via PUVA

Photochemotherapy & Photodynamic Therapy

• Photochemotherapy (PUVA) combines psoralen tablets & UVA, this method can be use to treat: psoriasis, cutaneous T-Cell lymphoma, atopic dermatitis, lichen planus, urticaria pigmentosa, pityriasis lichenoides, lymphatoid papulosis, pityriasis rubra pilaris, granuloma annulare, alopecia areata, localized scleroderma, graft-vs-host disease, vitiligo, HIV infected patient.
• Extracorporeal Photochemotherapy (Photophoresis) involves the irradiation of blood fractions used to treat: cutaneous T-Cell lymphoma, pemphigus vulgaris, systemic sclerosis, transplantation & graft vs host disease, SLE.
• Photodynamic Therapy PDT -Blue-U & Red-U selectively destroys target minimizing damage to vital structures by activating levulonic acid

Plasmaphoresis

• This is the separation of liquid the blood or plasma from the cells.
• Plasma can contain antibodies that attack the immune system.
• A machine removes affected cells while replacing with good cells

Hair Regrowth Systemic Meds

• Propecia (Finasteride) 1mg tab QD
• Nutrafol (OTC Nutraceutical) – 4 caps QID x 6 months
• Olumiant (Baricitinib) 2-4mg QD – JAK Inhibitor disrupting cytokine & growth factor signaling pathways in severe alopecia areata

Surgery in Dermatology

• Dermatologic Surgery introduction & approach
• Laser surgical procedures
• Skin resurfacing: chemical peels, dermabrasion, laser
• Wound Dressings
• Sclerotherapy for varicose & telangiectatic veins
• Tumescent Liposuction
• Soft Tissue Augmentation substances or fillers
• Hair Transplantation & Alopecia Reduction
• Cryosurgery
• Mohs Micrographic Surgery
• Nail Surgery

Surgical Instruments

• Biopsy Instruments include: Punch Bx (2-6mm), Shave Bx (scalpel or flex blade), or Scissor Bx

Introduction & Approach to Derm Surgery

• Factors include patient selection, infection control, surgical anatomy (danger zones), and local anesthesia
• Regarding local anesthesia, one must consider the mechanism of action, types of anesthesia, side effects, epinephrine vs no epinephrine, topical anesthetics, and "painless" local anesthesia (buffered solutions)
• Important suturing techniques are suturing materials (silk, prolene, vicryl or monocryl sutures) & needle size & shape
• Important elements are also suture placement, suture removal, stainless steel closure, super glue, and wound closure tapes
• Other considerations are excisional surgery, electrosurgery, healing by 2nd intention, local skin flaps, and general skin flaps & grafts

Electrosurgery

• The Hyfercator is used
• Electrosurgery cuts tissue
• Electrocautery coagulates tissue

Lasers in Dermatology

• LASER is an acronym for: Light Amplified by Stimulated Emission of Radiation
• Laser light is monochromatic (one color), highly collimated (parallel), intense, coherent (wavelengths of laser are in phase in space & time), and has a controllable beam of light allowing power to be delivered
• The principles of laser-skin interactions include photothermal interactions (vaporization or evaporation, selective photothermolysis) and photomechanical interactions that change tissue shape when exposed to the laser light.
• Photochemical interactions involve chemical reactions initiated by absorption of energy in the form of light.
• Clinical applications are vascular lesions (Port-wine stain, strawberry hemangioma, pyogenic granuloma, poikiloderma of Civatte, cherry angiomas, venous lake, angiokeratomas, Kaposi's sarcoma, spider veins), pigmented lesions, melasma, tattoos, and nevus of Ota, Ito & Mongolian spots
• Further applications of lasers are post-inflammatory hyperpigmentation, nevi, hair removal/transplantation, laser resurfacing, psoriasis, acne, striae, scars, and warts

Skin Resurfacing

• Techniques include chemical peels, dermabrasion, and microdermabrasion or power peels, including lasers using CO2 or Erbium: YAG lasers

Chemical Peels

• Involve wound classification
• Superficial Depth Peels: to the stratum granulosum or papillary dermis; very light using 10%-25% TCA Peel, α-Hydroxy fruity acids, salicylic acid, and rescorcinol, CO2 laser and light using 35% TCA peel
• Medium Depth Peel: penetrates through the papillary dermis to upper reticular dermis with 50% TCA
• Deep Depth Peels: involve the mid-reticular dermis and use Baker's Phenol Peel and requires a hospital procedure with monitoring
• Chemical peeling indications include: actinic keratosis, sun induced rhytids, pigmentary dyschromias, depressed scarring, and acne vulgaris
• Chemical peel complications include: pigmentary changes, infection (bacterial, fungal, or viral), prolonged erythema, textural changes, and milia

Dermabrasion

• It is indicated when surgically abrading or planing defects of the epidermis & dermis with a rapidly rotating wire brush or diamond fraise
• Complications: scarring, pigmentary changes, persistent erythema, infection

Laser Resurfacing

• Laser types include CO2 and Erbium: YAG Lasers
• Side effects and complications- most efficacious with the most risk include: predictable erythema, pruritus, swelling, oozing and crusting; pigmentary which is hyperpigmentation, permanent hypopigmentation; infection bacterial, viral, and yeast.
• Dermatitis can include eczema and scarring, which can be atrophic, hypertrophic, or keloidal
• Follicular acne, acneiform eruption, or milia

Sclerotherapy

• There is intravascular introduction when sclerosing substance to treat superficial telangiectases, venulectasis & mid-sized varicose veins
• There is surgical ambulatory phlebectomy or ligation of the saphenofemoral junction
• Sclerotherapy Indications: Pain, Major tributaries of greater & lesser saphenous veins, Major perforator reflux, Lateral venous system varicosities, Cosmetic
• Sclerotherapy Contraindications include: Reflux @ the saphenofemoral or saphenopopliteal junction, Nonambulatory patient, Obesity, Deep venous thrombosis (DVT), Allergy to sclerosing agent, Arterial obstruction, and Pregnancy

Sclerotherapy Technique

• Includes pretreatment evaluation and sclerosing solutions
• Sclerosing solutions can be hypertonic saline, hypertonic solutions & dextrose, polidocanol (detergent-based urethane), sodium tetradecyl sulfate (long-chained fatty acid salt), sodium morrhuate (5% solution of the salts of saturated & unsaturated fatty acids in cod liver oil)
• Chemical irritants also are used (polyiodinated iodine and chromated glycerin)
• Complications: Post-sclerotherapy hyperpigmentation, Telangiectatic matting, Cutaneous Necrosis/Ulceration, Superficial Thrombophlebitis, Pulmonary Embolism, Arterial Injection
• Alternative Approaches: Surgical Ligation & Limited Stripping, Ambulatory Phlebectomy, Intense pulsed Light Source (IPL), Lasers (flash-lamp pumped-dye laser Sclerolase, Nd:YAG

Tumescent Liposuction.

• It is a safe & effective technique for removing adipose tissue to effect a change of contour using local anesthesia

Soft Tissue Augmentation Substances

• Injectable Bovine Collagen (Discontinued): Zyderm I, Zyderm II, Zyplast
• Injectable Bio-engineered Collagen (Discontinued): Cosmoderm, Cosmoplast
• Fibril (microfibrillated cellulose)
• Fat Transplantation
• Neurotoxins: Botox, Dysport, Xeomin, Jeuveau
• Hyaluronic Acid
• Calcium hydroxylapatite
• Poly-L-lactic acid
• Gortex implantation

Hair Replacement Techniques for Androgenic Alopecia (Male Pattern Baldness)

• Hair Transplantation
• Alopecia Reduction
• FUT (Follicular Unit Transplantation)
• FUE (Follicular Unit Extension)
• DHI (Direct Hair Implant) by Choi needle
• PRP (Plasma Rich Protein) Injections
• Micrographs (1-2 hairs), Mini-slit graft (3-5 hairs), Mini graft (5-12 hairs), Standard graft (8-30 hairs)
• Complications -infection, minimal growth, accelerated hair loss, cobblestoning, A-V fistulas, temporary curly hair, epidermal cysts, osteomyelitis, indented "grooves", keloids, telogen effluvium, hyperfibrotic healing, hypertrophic scars, chronic folliculitis/wound dehiscence
• Alopecia Reduction Definition:excision of an area of alopecia or future alopecia

Cryosurgery

• Cold has been an adjunct in medicine since the Egyptians at 2500 BC
• CO2 was 1°cryogen in early 1900s (-109° F)
• Liquid N2 has been used since 1948 (-320° F)
• Cryosurgery: Technique utilizes heat removed from tissues by application of cold. It is effective in treating benign, premalignant & malignant lesions
• Side effects: Expected effects including edema, vesicles, bullae, weeping, eschar formation; Infection; Abnormal Scarring; Pigment Alteration; Nerve Damage; Insufflation of Soft Tissue; Alopecia

Mohs Micrographic Surgery Technique

• Neoplasm identified & marked
• Local anesthetic infiltrated
• Curettement of lesion to delineate the margin of the tumor; Neoplasm is removed using a tangential incision circumferentially around the tumor with the deep margin excised horizontally & parallel to the skin surface.
• Specimen divided, tissue sides are color-coded & a map created, duplicating the tissue orientation & color locations
• Tissue is presented to the technician, inverted & sectioned on a microtome on-site
• Surgeon reviews the sections microscopically, marking areas of residual tumor on the map.
• This process continues until tumor is clear, then the site is repaired and reconstructed

Nail Surgery

• Procedures: Avulsion (partial, complete), Hematoma Drainage, Puncture, Paring, Biopsy (nail clipper biopsy, shave biopsy, incisional biopsy, punch biopsy), Ingrown Nail, Removal of longitudinal melanonychia, Verruca vulgaris surgical treatment