Table 1.

The most common skin conditions for which ECS modulation could be an effective therapeutic option.

Affection (Estimative Costs around the Current Course of Therapy)	Current Drug Therapies		Drawbacks/ Most Significant Adverse Effects	Reference
Psoriasis (between USD 23.9 and USD 35.4 billion annually in the US	topical agents	vitamin D analogues corticosteroids	poor therapy responses	[35,112]
	phototherapy	NB-UVB PUVA	major risks of skin cancer
	standard systemic	acitretin	dry skin, hair loss, hyperlipidemia, hepatotoxicity
		ciclosporin	hypertension, irreversible renal toxicity
		methotrexate	bone marrow suppression, liver fibrosis, teratogenicity, hepatitis
	biologic agents	TNF IL-17 L-23 inhibitors	individualized therapy regimen
	small molecule inhibitors	apremilast dimethyl fumarate	used only in studies
Atopic dermatitis (USD 3.8 billion annually in the US)	topical moisturizers	glycerin, alpha hydroxy acids, hyaluronic acid, sorbitol, urea, lanolin, mineral oil, olive oil, silicone, collagen, elastin, glyceryl stearate, shea acid, stearic acid	a large number of studies lacking any significant relevance regarding the efficacy	[113,114]
	topical corticosteroids	clobetasol, fluocinonide, betamethasone, triamcinolone, fluticasone budesonide, hydrocortisone	atrophy, striae, rosacea, perioral dermatitis, acne, purpura, hypertrichosis, alteration of the skin’s pigment, sluggish wound healing, worsening of skin infections	[115]
	topical calcineurin inhibitors	tacrolimus pimecrolimus	skin burning, increased bone growth and decreased bone density, inhibition of the hypothalamic-pituitary-adrenal axis in children	[116,117,118]
	phototherapy	UVB	xerosis, erythema, actinic keratosis, skin damage tenderness, possible carcinogenic risk	[118,119]
	systemic immunotherapy	cyclosporine azathioprine	headache, serum lipid TSH elevation, teratogenicity, liver dysfunction, leukopenia, gastric ulcer, osteoporosis, glaucoma	[120]
Allergic contact dermatitis (USD 5.3 billion in the US in 2015)	systemic corticosteroids	clobetasol, betamethasone, diflorasone, fluocinonide, halcinonide, mometasone furoate, fluocinolone acetonide, desoximetasone, triamcinolone acetonide, alclometasone dipropionate, hydrocortisone, dexamethasone, prednisolone, methylprednisolone	atrophy, infections, hypertrichosis, allergic reactions, problems with systemic absorption	[36,37,121]
	calcineurin antagonists	cyclosporine	risk of malignity	[36,38]
	ultraviolet therapy	PUVA UVB	lentigines (freckling), photoaging, precancerous lesions, actinic keratoses, skin cancer, hyperpigmentation, redness, dryness, pruritus, herpes simplex virus reactivation, polymorphic light eruption	[36,39]
Asteatotic eczema (USD 5.3 billion annually)	topical steroid	hydrocortisone, glucocorticoid, nonfluorinated steroids (hydrocortisone valerate, hydrocortisone probutate, mometasone furoate), fluorinated steroids (dexamethasone, triamcinolone, fluocortolone, flumethasone, betamethasone)	skin atrophy, striae atrophicans, xeroderma, delayed wound repair, capillary telangiectasia, rosacea-like dermatitis, steroid purpura, steroid acne milium, pigmentation disorder, acne uncontrollable, hyper-pilosis	[36,40,41]
	phototherapy	UVA (UVA-1) UVB PUVA	suppressing immune system	[40]
Acne (acne is thought to cost the economy USD 3 billion annually)	topical retinoids	adapalene, isotretinoin, motretinide, retinoyl-β-glucuronide, tazarotene, tretinoin	used in various combinations, all of these topical treatments disrupt the skin’s natural barrier, requiring frequent treatment changes	[42,43,44]
	topical antibiotics	clindamycin, erythromycin	disruption of the skin’s natural barrier
	diverse topical agents	azelaic acid, benzoyl peroxide, chemical peels, corticosteroids, dapsone, hydrogen peroxide, niacinamide, salicylic acid, sodium sulfacetamide, sulfur triclosan	specific adverse events
	systemic retinoids	isotretinoin	hematological/lymphatic disorders, immune system disorders, metabolic and nutritional disorders
	systemic antibiotics	azithromycin, clindamycin, co-trimoxazole, doxycycline, erythromycin, levofloxacin, minocycline, roxithromycin	specific adverse events
	other systemic agents	hormones, clofazimine, corticosteroids, ibuprofen, zinc sulfate	specific adverse events
Seborrhea (in 2021, the value of the global seborrheic dermatitis market was estimated to be USD 2.2 billion)	antifungals	itraconazole, terbinafine, fluconazole, ketoconazole, pramiconazole	itching, burning sensation, dryness	[108,109,122]
	corticosteroids	prednisone	skin atrophy, telangiectasias, folliculitis, hypertrichosis, hypopigmentation	[109]
	calcineurin inhibitors	pimecrolimus	skin malignancy lymphoma	[123]
	phototherapy	UVB PUVA red and blue LED light	burning itching sensation genital tumor	[123]

Abbreviations: NB-UVB, narrowband ultraviolet B radiation; PUVA, psoralen ultraviolet A radiation; TNF, tumor necrosis factor; IL, interleukin; AD, atopic dermatitis; ACD, allergic contact dermatitis; UVB, ultraviolet B radiation.