Systemic therapy is required in many dermatological, allergic, and venereal diseases when topical treatment is not sufficient. Use of systemic therapy has increased in the last decades, especially after introducing new agents in dermatological therapy (i.e. biologicals, small molecules). Before introducing therapy, it is mandatory to establish a correct diagnosis, evaluate potential contraindications and consider possible side effects including drug interactions during the treatment.
9.3.2 Pharmacologic Basics of Systemic Therapy in Dermatology
Antibiotics are used to treat infectious skin and venereal diseases and some other diseases due to their antimicrobial, anti-inflammatory, and immunomodulatory effects. In infectious diseases, antibiotics should be prescribed according to the infection type (typing of resistance pattern) and according to the spectrum of action. Antimicrobial resistance development should be avoided whenever possible (definite indication, avoid broad-spectrum antibiotics). Indications: primary (i.e. disseminated impetigo contagiosa, Lyme disease) and secondary (i.e. severely impetiginized eczema), deep bacterial infections of the skin as well as venereal diseases (i.e. syphilis, gonorrhoea), primarily non-infectious, but pathogen-associated diseases (i.e. severe acne ), primarily non-pathogen-associated skin diseases (i.e. nodular rosacea).
Antihistamines are competitive antagonists acting on the histamine receptor. In dermatology, most commonly used are H1 blockers as they are indicated for the treatment and the prophylaxis of allergic and pseudoallergic reactions. First-generation H1 blockers had sedative side-effects, which has been avoided in the second-generation antihistamines which do not cross the blood-brain barrier. Indications include urticaria, allergic rhinitis and conjunctivitis; intravenously administered antihistamines are the mainstay of the initial treatment of anaphylaxis.
Systemic antimycotics are used in the treatment of widespread or deep localised dermatomycoses as well as mycotic infections that affect hair and nails. Most commonly used groups of antimycotics are azole-type antifungals (i.e. fluconazole, itraconazole for the treatment of dermatophytes and yeasts) and allylamine derivates (i.e. terbinafine for the treatment of dermatophytoses). Griseofulvin is still used in the treatment of dermatophytoses.
Glucocorticoids are the most widely used drugs in dermatology. Their main mode of action are anti-inflammatory, immunosuppressive and antiproliferative. Glucocorticosteroids are indicated in the therapy of inflammatory dermatoses, autoimmune dermatoses, granulomatous dermatoses, and other diseases that are not classified in one of these three groups. They are absolutely contraindicated in active untreated tuberculosis, systemic mycoses and ocular herpes simplex. The list of relative contraindications is much broader, including chronic gastritis, esophagitis and gastrointestinal bleeding, severe osteoporosis, glaucoma, depression etc. In those patients, glucocorticosteroids can be introduced if needed but with special prophylactic measures. Most common side effects are diabetes mellitus, hypertension, increased susceptibility to infections, osteoporosis, aseptic bone necrosis, gastrointestinal bleeding etc.
Retinoids include derivatives of vitamin A acid and substances with different chemical structures but related biological activities. They belong to the steroids superfamily.
Five groups of retinoids are available for the use in dermatology:
- isotretinoin and
The most common indications for use are psoriasis, palmoplantar hyperkeratosis, PRP (Pityriasis Rubra Pilaris), lichen planus for acitretin; refractory hand eczema for alitretinoin; cutaneous T-cell lymphomas for bexarotene; and severe and refractory forms of acne for isotretinoin. Contraindications: familial and clinically relevant acquired lipid metabolic disorders, simultaneous administration of tetracyclines, severe diabetes, pregnancy or plans to become pregnant and breastfeeding due to teratogenicity. Contraceptive care measures should be followed seriously.
The two most important antimetabolites in systemic dermatological therapy are methotrexate and azathioprine. Methotrexate has a cytotoxic and immunomodulatory function. It is indicated in severe psoriasis, psoriatic arthritis, dermatomyositis, morphea, and some other dermatoses. It is usually prescribed once a week orally or subcutaneously. Contraindications for the therapy are pregnancy and lactation, acute infection, bone marrow depression and liver diseases. To avoid MTX overdose, folic acid should be given orally in parallel. Azathioprine is a cytotoxic agent used as an immunosuppressant. Main indications are autoimmune blistering diseases (in combination with glucocorticoids – as steroid-sparing agents). Other indications include vasculitis, lupus erythematosus, and pyoderma gangrenosum.
Chloroquine and hydroxychloroquine are most commonly given in dermatology for the treatment of cutaneous and systemic lupus erythematosus. Glucose-6-phosphate dehydrogenase deficiency should be excluded before introducing therapy. Contraindication for introducing the drug is retinopathy, visual field restrictions, pregnancy and lactation. Ophthalmological consultations should be done before starting the treatment and in most patients after five years, in risk groups every year.
Dapsone is an antibacterial and anti-inflammatory drug, in dermatology most commonly used to treat dermatitis herpetiformis, linear IgA dermatosis and nodular vasculitis. Glucose-6-phosphate dehydrogenase deficiency should be excluded before introducing therapy. Methemoglobin should be checked regularly; hemolytic anaemia and agranulocytosis can occur.
Biologics and small molecules
Biologics are monoclonal antibodies which target specific proteins involved in the pathogenesis of various dermatological diseases, including psoriasis and metastatic melanoma.Small molecules are agents with a low molecular weight that can pass through cell membranes to modulate intracellular targets. They are most commonly used in the treatment of psoriasis and atopic dermatitis.
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