10.1-1 Dermatologic Drugs (Al-Mehdi)

Molluscum contagiosum

"Water blisters" (look like blisters but are translucent papules) in clusters. Nodular, pale, firm, pearl-like lesions usually 2 to 10 mm in diameter, painless and umbilicated. Caused by DNA poxvirus. Rx: IMIQUIMOD cream (TLR 7/8 agonist - 7 inactivates NFkF (TF) which normally leads to gene expression leading to activaiton of natural killer cells->production of IFNgamma->activates B-cells that produce IgG2A).

TEN

(Toxic Epidermal Necrolysis) Delayed hypersensitivity. Widespread subepidermal blistering and sloughing. Fever and lung, bladder, GI mucosal involvement (staphylococcal scalded skin syndrome does not involve mucosa). → Multiorgan failure → High mortality (>30%). Variant of TEN: Stevens-Johnson syndrome: damage restricted to mucosa.

Timeline for desquamation and replacement

14 days to move from stratum basale to stratum granulosum. Another 14 days to move through stratum corneum. otal of 28 days. The major function of stratum corneum is barrier. T The cornified cell envelope (protein envelope and lipid envelope) is the major barrier element

Folliculitis

: hair follicle infection ± pus Furuncle: abscess from a folliculitis

Captopril

ACE inhibitor

Rx of pemphigus: IMMUNOSUPPRESSIVE AGENTS

AZATHIOPRINE MYCOPHENOLATE MOFETIL METHOTREXATE CYCLOPHOSPHAMIDE

Stages of Dermatitis in Eczema

Acute stage - wet, chronic stage -dry

Erysipelas and Cellulitis

Acute, spreading infections of dermis and hypodermis. Most frequently by Group A Streptococcus (erysipelas) or S. aureus. Rx: CIPROFLOXACIN (fluoroquinolone) CEFIXIME (2nd gen cephalosporin) AMOXICILLIN + CLAVULANIC ACID (ß-lactamase inhibitor) DOXYCYCLINE

Disorders of T-Cell Dysregulation

Allergic Contact Dermatitis, Atopic Dermatitis (Eczema), and Psoriasis

Acyclovir

Antiviral

Cutaneous Anthrax

Bacillus anthracis. Naturally occurring zoonotic form. Vesicle progresses to eschar (hard, black crust). Severe tissue edema, lymphadenopathy, systemic signs Rx: CIPROFLOXACIN or DOXYCYCLINE for 60-100 days (spores persist in lymph nodes) Prophylaxis: Same as Rx

Retinoid MOA

Bind to zinc fingers - increasing or decreasing transcription of genes. 3 RARs (alpha, beta, gamma - gamma in human skin) and 3 RXRs (alpha, beta, gamma - alpha in human skin)

drug-induced pemphigus

Captopril and penicillamine contain sulfhydryl groups that react with desmoglein and make them immunoreactive

Penicillamine

Chelator, immunomodulator: copper and sometimes lead, mercury, arsenic. Used in Wilson's disease and rheumatoid arthritis

Ecthyma

Ecthyma: When impetigo extends into dermis, Chronic, well-demarcated, deep ulcers with crust. Rx: PHENOXYMETHYLPENICILLIN (Penicillin V) CLOXACILLIN TOBRAMYCIN (aminoglycoside) [Vestibulotoxic: STREPTOMYCIN, GENTAMICIN Nephrotoxic: NEOMYCIN , TOBRAMYCIN, GENTAMICIN] Topical: MUPIROCIN ointment in the nares and on skin

Impetigo

Epidermal inflammation due to infection. Non-bullous and bullous. "Honey-crusted" erosions.Rx: Staphylococcus aureus - CLOXACILLIN Group A Streptococcus - PHENOXYMETHYLPENICILLIN (PENICILLIN V)

Bullous Impetigo

Epidermolytic toxin of S. aureus cleaves desmoglein-1 → blistering. If blisters are widespread = staphylococcal scalded skin syndrome, SSSS. DDx with TEN (toxic epidermal necrolysis): TEN also has mucosal involvement.

Three forms of drug-induced skin disease

Erythroderma, TEN (toxic epidermal necrolysis), and Drug-induced hypersensitivity syndrome

Fungal: Ringworms

Etiology: Trichophyton, Microsporum and Epidermophyton genera Location: dermatophytoses (they affect skin) Tinea corporis (body) Tinea cruris (groin) Tinea pedis (athlete's foot) Tinea manuum (hand) Tinea capitis (head) Tinea unguium (nail) Rx: Topical: CLOTRIMAZOLE, TERBINAFINE (teratogenic effects - do not use in pregnancy) Systemic: ITRACONAZOLE, TERBINAFINE, GRISEOFULVIN (inhibits microtubules - like colchicine and paciltaxil).

Pemphigus foliaceus and vulgaris desmoglein (Dsg) compensation.

Foliaceus - affects mainly Dsg 1 which is found in large concentrations on outer layers of skin and to a minor extent in the mucous membrane (largely unaffected). Vulgaris - one form affects mainly Dsg 3 found mainly in mucous membrane (seperates skin from basal layer). Another form affects Dsg1 and 3 and it causes major disruption in lower layers of mucous membrane and skin.

Rx of pemphigus: corticosteroids

High potency topical steroids and PREDNISONE

Rx of Ichthyoses

Hydration: humid climates, long baths. Lubrication: lotions, creams, oils, ointments, or petrolatum. Keratolysis: UREA, SALICYLIC ACID, LACTIC ACID, GLYCOLIC ACID Propylene glycol (40-60% in water). Retinoids: ISOTRETINOIN, ACITRETIN.

systemic retinoids and SEs

ISOTRETINOIN, ACITRETIN, AND BEXAROTENE | Teratogenicity, hair loss, tendon and ligament calcification, osteoporosis. Pregnancy must be avoided, and the use of retinoids in women of childbearing age therefore requires careful monitoring

Ichthyosis types

Inability of desquamation or exaggerated proliferation of cells. Ichthyosis vulgaris - Filaggrin mutation. X-linked ichthyosis - Steroid sulfatase mutation. Lamellar ichthyosis - Autosomal recessive. Mutation of transglutaminase 1 or ABC A12 or lipoxygenase. Epidermolytic hyperkeratosis - Keratin 1 & 10 mutation.

Rx of pemphigus: MODULATORS OF ANTIBODY LEVELS:

Intravenous γ-globulin (IVIG) Plasmapheresis

Disorders of Epidermal Differentiation and Keratinization

Irritant Contact Dermatitis and Ichthyosis

Th0

Naive T-cell (inactive)

Photo Rx of psoriasis

PUVA, UVB

Major complication of psoriasis and etiology

Psoriasis >2% of US population. psoriatic arthritis (30% of patients with psoriasis). Psoriasis is caused by multiple factors (e.g. environmental, temperature etc.)

Erythroderma

Red skin (inflammation) of all of skin Etiology: Atopic and seborrheic eczema, Psoriasis, Drugs (sulfonamides, sulfonylureas, penicillin, allopurinol, captopril) Idiopathic, Leukemias, Complications: The skin is one of the largest organs of the body. Inflammation of the whole organ causes metabolic and hemodynamic problems

Dx of Psoriasis

Symmetry of lesions, Extensor distribution, Auspitz sign, Sharply demarcated lesions, and Silvery scale

IL-2 as an autoreceptor ligand

TCR signaling ->activates calcineurin (removes phosphate from NFAT-P) to *NFAT (transcription factor)* ->makes IL2->exocytosed and binds to surface receptor IL-2R signaling->activates mTOR ->altered gene expression resulting in IL-12, 1, 6, or 23

Rx of pemphigus: other

TETRACYCLINE OR ERYTHROMYCIN (if infective) DAPSONE Topical TACROLIMUS

Products of Th17 and Th1 and their purpose

Th1 - TNFalpha and Th17 - IL-17. They bind to receptors on the keratinocyte which release other cytokines (e.g. defensis, TNF-alpha,IL-1 etc.) which further activates Langerhans cell and completes the cycle.

Antibacterial Drugs in Acne

Topical or systemic: TETRACYCLINE: systemic (photosensitivity and brown discoloration of teeth - cannot be prescribed to young children (also interferes with calcium metabolism affecting bones and teeth))

Herpes zoster

Varicella zoster virus (VZV) causes chickenpox and herpes zoster. 'Shingles' is due to reactivation of VZV in sensory ganglia. Prodromal phase - tingling or pain. Dermatomal painful blister distribution. Complications: Post-herpetic neuralgia. Ophthalmic zoster. Motor neuropathy. Rx: *ACYCLOVIR*, VALACYCLOVIR, and FAMCICLOVIR

Genetic Diseases with Eczema

Wiskott-adldrich: x-linked immunodeficiency and phenylketonuria

If the retinoids increase keratinocyte proliferation, then how are they useful to treat acne, psoriasis, and ichthyosis that are characterized by hyperkeratosis. Wouldn't retinoids exacerbate these diseases?

You are creating new cells with normal ability for desquamation and push out dead layer that is blocked

ACITRETIN

a systemic drug - for severe psoriasis

Cyclosporine and tacrolimus

bind and inactivate calcineurin and inhibit T-cell expression of IL-2 and downstream products

plakoglobin

binds desmocollin and desmoglein (between cells) and desmoplakin (within cell)

Comedones

blackheads

Carbuncle

boil): interconnecting abscesses involving contiguous hair follicles. Abscess: Collection of pus and tissue destruction. Etiology: MSSA, MRSA Rx: MUPIROCIN ointment to eliminate nasal carriage CIPROFLOXACIN (fluoroquinolone) CEFIXIME (2nd gen cephalosporin) AMOXICILLIN + CLAVULANIC ACID (ß-lactamase inhibitor), CLOXACILLIN (penicillinase-resistant)

Epidermolysis bullosa affects

collagen VII in dermis

Topical Rx of psoriasis

corticosteroids, calcipotriol (vit.D analog), anthraline, coal tar, and retinoid (tazarotene)

Rx of pemphigus

corticosteroids, immunosuppresive agents, modulators of antibody levels (IV gamma-globulin), and other

T-cell will not work without ______

costimulation of CD86 and CD80- on the langerhans cell interacting with the CD28 on the T-cell.

Signalling transduction in T-cell leads to exocytosis of _______

cytokine, IL-2. An autocrine signalling occurs resulting in altered gene expression and production and exocytosis of IL-12 transforming other Th0 into Th1 or IL-1,6, or 23 transforming other Th0 into Th17 (or others). Clonal expansion.

Dermal _____ with prolonged corticosteroid use

dermal atrophy. Corticosteroids reduce matrix collagen and glycosaminoglycan production → dermal atrophy, drying, cracking, tightening of the skin

Pemphigus affects

desmosomes

Rx of Eczema

emollients, topical corticosteroids, and other immunosuppressants (e.g. cyclosporine, tacrolimus, and pimecrolimus)

Langerhans cells

epidermal macrophages that help activate the immune system. An antigen presenting cell. It presents the T-cell with the antigen and the T-cell will make final determination if antigen is foreign. PD-1L inhibits activation of T-cell PD=programmed death. CD86 and 80 must switch from CTLA to CD28 (costimulation).

Systemic Rx of psoriasis

etanercept, ustekinumab, adalimumab, cyclosporine, methotrexate, and acitretin

Diets high in _______ seem to be protective against the development of psoriasis

fish oils

BEXAROTENE

for cutaneous T-cell lymphoma.

Acne - genetic portion

genetic susceptibility->pilosebaceous duct (hypercornification)->blockage of pilosebaceous duct-> form comedones->inflamed papule->rupture into dermis->increased chemotactic factors (e.g. IL-8) Neutrophil recruitment->pustule.

Granulysin

has antimicrobial actions and can induce apoptosis. Affected in SJS and TEN

Pemphigoid affects

hemidesmosomes

Sirolimus

inactivates mTOR blocking IL-2R signaling and downstream products of IL-12, 1, 6, or 23

Acne through puberty

increased pubertal androgens->sebum production (sebaceous hyperplasia)->increased cutibacterium acnes->hydrolyses lipids to produce pro-inflammatory FAs->inflamed papule->rupture into dermis->increased chemotactic factors (e.g. IL-8) Neutrophil recruitment->pustule.

Laminin

key basement membrane glycoprotein. An intermediate filament that is a part of cytoskeleton.

Auspitz sign

pinpoint bleeding after a silvery scale is removed - characteristic of psoriasis. Damage proliferated (now tortuouscapillary) loops found in psoriasis.

Teratogenic effect

producing malformations (in the developing embryo)

desmoplakin

protein in desmosome plaque that is relatively large and extended dimer that forms the junction between intermediate filaments and the TM adhesion proteins (desmoglein and desmocollin). Binds keratins (which are attached to each other by filaggrin).

Atopic Dermatitis (Eczema): Sx

pruritus, flexural eczema

Tars and anthralin

psorasis drugs: inhibit keratinocyte proliferation

Topical retinoids for Rx of acne

retinoids are vitamin a derivatives (carotene is two molecules of vitamin A joined together)

Hyperkeratotic disorders usually interfere with _______

sweat gland function, leading to hypohidrosis and heat intolerance due to loss of evaporative cooling

Rx of psoriasis

systemic (high toxicity high effectiveness), photo (mild toxicity mild effectiveness), and topical ( low toxicity low effectiveness)

ISOTRETINOIN (13-cis-retinoic acid)

systemic retinoid- is used for cystic and conglobate acne, psoriasis

Stevens-Johnson Syndrome

variant of TEN-damage restricted to mucosa

CALCIPOTRIOL synonym CALCIPOTRIENE

vitamin D derivative - antiproliferative and immunomodulatory effects.