الفهرس 
Pulse GC TherapyOnly 14 pages are availabe for public view
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Abstract
Pulse therapy means the administration of suprapharmacologic doses of drugs in an intermittent manner to enhance the therapeutic effect and reduce the side effects. In context of corticosteroids, pulse therapy refers to discontinuous i.v. infusion of high doses of the medication, defined as treatment with more than 250 mg prednisone or its equivalent per day, for one or more days. However GCs may also be administered in an intermittent manner orally or even topically for treatment of some dermatologic diseases.
Regarding parentral pulse steroid therapy methylprednisolone is administered at a dose of 20-30/kg (500-1000 mg) per pulse. Dexamethasone is administered at a dose of 4-5 mg/kg (100-200 mg) per pulse. Repeated pulses are given at intervals of 24-48 hours, i.e., daily or on alternate days, usually for three or six pulses. Single dose administration regimens have also been described.
Clinical uses of pulse GC in dermatology include pemphigus vulgaris, paraneoplastic pemphigus, bullous pemphigoid, Reiter’s disease, pemphigoid gestationis, SLE and subacute cutaneous lupus erythematosus. dermatomyositis/polymyositis, Sweet’s syndrome, generalized lichen planus, erythema multiforme major, EBA, AA, subcorneal pustular dermatosis, progressive systemic sclerosis, polyarteritis/temporal arteritis/Wegner’s granulomatosis, pyoderma gangrenosum, KD, urticarial vasculitis, eosinophilic fasciitis, cytophagic histiocytic panniculitis and cutaneous T-cell lymphoma.
Side effects of pulse GC therapy include immediate an long term side effects, regarding the immediate side effects, they include hypotension or hypertension, peripheral edema, electrolyte abnormalities, cardiac arrhythmias, congestive heart failure, pulmonary edema, anaphylaxis, arthralgias, glucose intolerance, dyspepsia, metallic taste, gastrointestinal bleeding or perforation, insomnia, euphoria, psychosis, depression, Facial flushing, seizures and sudden death. While the Long term side effects include generalized pruritus, pancreatitis, urinary tract infection, otitis media, septic arthritis, pneumonia, posterior subcapsular cataract, reactivation of pulmonary tuberculosis and candidiasis.
Oral minipulse therapy implies use of cycles of pulse dose corticosteroids in much smaller doses compared to the usual pulse therapy The steroid used most commonly used is either betamethasone or dexamethasone at a dose of 5mg or approximately 0.1mg/kg body weight, methylprednisolone has also been tried but with a relatively larger dose.
Regarding the clinical uses of oral pulse steroid therapy in dermatology, they include vitiligo, AA, lichen planus, recalcitrant necrobiotic xanthogranuloma, pemphigus vulgaris.
As for the uses of topical pulse steroid therapy in dermatology, they include psoriasis, atopic dermatitis and EBA.
Cyclophosphamide, an alkylating agent, has been used as a carcinotoxic drug in the treatment of malignancies and as an immunosuppressant in the treatment of various autoimmune disorders. Pulse i.v. cyclophosphamide therapy is given at a dose of 500 to 1000 mg/m2 over 1 hour.
Its Clinical uses in dermatology include pemphigus vulgaris, bullous pemphigoid, CP, paraneoplastic Pemphigus, herpes gestationis, TEN, pyoderma gangrenosum, Wegener’s granulomatosis, lymphomatoid granulomatosis, rheumatoid vasculitis, polyarteritis nodosa, severe necrotizing vasculitides, SLE, dermatomyositis, relapsing polychondritis, Behcet’s disease, scleromyxedema, lichen myxedematosus, severe eczematous dermatitis, mycosis fungoides, histiocytosis X, multicentric reticulohistiocytosis, and cytophagic histiocytic panniculitis.
Toxicity and adverse effects include hematologic toxicity, gastrointestinal toxicity, gonadal damage, urologic damage, carcinogensis, opportunistic infection, alopecia, cardiotoxicity, pulmonary damage, teratogenicity, water intoxication (hyponatremia), hypersensitivity, anaphylaxis, hepatotoxicity, anagen effluvium, mucositis, hyperpigmentation of skin and nails, transient cerebral dysfunction, fever, and fatigue.
Intravenous pulse cyclophosphamide also proved to be effective in treatment of SLE after plasmapheresis as it is toxic to B cell proliferation. Few reports have suggested that plasmapheresis in conjunction with pulse i.v. cyclophosphamide may improve disease in patients with refractory bullous pemphigoid recalcitrant CP, pyoderma gangrenosum and severe pemphigus vulgaris.
The original rationale for the therapeutic application of Ig was prevention and treatment of infectious diseases. With the description of agammaglobulinemia, substitution therapy became the primary indication for the use of Ig. Off-label use of IVIg is increasing in dermatology. There is accumulating evidence that IVIg is effective in the treatment of various skin diseases, especially immunobullous diseases refractory to conventional therapies despite the lack of evidence from large, multicenter, randomized controlled trials.
The dose of IVIg used in patients with primary antibody deficiency is 200 mg/kg every two weeks, however, when it is used for immunomodulation the dose is most frequently 2 g/kg per month. IVIg may be infused as five daily doses of 400 mg/kg each. However, some studies found a superior effect of IVIg when given as a single full dose rather than divided doses. Repeated infusions of IVIg, usually 2 g/kg at 4–6-week intervals, are needed.
Clinical uses of IVIg in dermatology include immunodeficiency syndromes and some off-label dermatologic uses such as in autoimmune bullous disease, urticaria, TEN, connective tissue diseases, vasculitis and others like psoriasis, atopic dermatitis and pyoderma gangrenosum.
Side effects of IVIg therapy include headache, backache, myalgia, fever, anaphylaxis, transmission of hepatitis C, acute hemolysis, aseptic meningitis, urticaria and erythema multiforme.
Prostaglandin E1 is a prostanoid that has numerous biological actions such as inhibition of receptor-mediated stimulation of platelet aggregation, cytoprotection, vasodilation and suppression of antibody formation.
Prostacyclin exerts a potent vasodilatory action by inducing cyclic adenosine monophosphate and by an antiproliferative effect on smooth muscular cells, as well as inhibition of platelet aggregation. It also improves the malleability of the red cells and reduces the leucocitary adhesion to endothelial cells.
Clinically PGE1 and PGI2 are used in dermatology to treat connective tissue diseases and Raynaud’s disease showing some adverse effects like hypotension, diarrhea, headache, nausea, flushing, and jaw pain.
Itraconazole is a triazole antifungal agent with a broad activity spectrum and favorable pharmacokinetic and safety profiles. Itraconazole is keratinophilic and tends to accumulate in skin, hair and nails, where it may persist at therapeutic levels long after completion of treatment (stratum corneum: 2–4 weeks, nails: 6–9 months). It’s used at a dose of 200 mg twice daily for 7 days in most cases and to be repeated every month if needed. It’s used to treat superficial mycoses, yeast infections and deep cutaneous (subcutaneous) infections. Treatment with itraconazole pulse may cause headache, gastrointestinal disorders, dizziness and skin reactions.
There are distinct advantages to treating tinea capitis with a dose of griseofulvin that is administered on one, two or three occasions, e.g. improved compliance and reduced cost. Such a regimen would become a consideration if it could be demonstrated that it had an efficacy and adverse effects profile that were similar to, or better than continuous therapy.
Intermittent dosage schedules of ketoconazole, 400mg/day has been reported with varying degree of success in treatment of pitryasis versicolor and other superficial fungal infections.
When fluoconazole is used to treat superficial mycoses including onychomycosis, the dosage range is generally 150 mg once weekly for skin infections and 150-300 mg once weekly for onychomycosis.
Available studies used 250 mg twice daily given for 1 week, with 3 weeks off between successive active treatment courses, for 3 or 4 repetitions. Intermittent terbinafine was reported in treatment of tinea capitis, dermatophytes and onychomycosis.
Azithromycin is a new macrolide, which has a superior pharmacokinetic profile when compared with other macrolides. It penetrates tissues rapidly, where it remains for prolonged periods. It’s used to treat acne vulgaris, pyoderma, abscesses, infected wounds, ulcers, and erysipelas. Azithromycin may cause diarrhea, nausea, abdominal pain, palpitations, angina, dyspepsia, flatus, vomiting, melena, jaundice, vaginal monilia, vaginitis, nephritis, dizziness, headache, vertigo, somnolence, fatigue, angioedema, photosensitivity and intrahepatic cholestasis.
Methotrexate has a triple anti-inflammatory, antiproliferative and immunosuppressant action. Weekly dosages of methotrexate usually range from 7.5 to 25 mg given orally or parenterally.
In dermatology, methotexate is used to treat:
Psoriasis (erythrodermic; moderate to severe arthropathic; pustular; extensive chronic plaque psoriasis; refractory to phototherapy and/or retinoid; extensive ungual psoriasis).
Bullous diseases (bullous pemphigoid; pemphigus vulgaris and foliaceus; cutaneous porphyria; epidermolysis bullosa acquisita).
Collagen diseases (lupus erythematosus; dermatomyositis; scleroderma).
Vasculitis and neutrophilic dermatoses (polyarteritis nodosa, Behcet’s disease, leukocytoclastic vasculitis, Kawasaki disease, pyoderma gangrenosum).
Other indications: (Atopic dermatitis; Sézary syndrome; pityriasis rubra pilaris; pityriasis lichenoides and varioliformis acuta; Reiter’s syndrome; Sarcoidosis, lymphomatoid papulosis; mycosis fungoides; keratoacanthoma; cutaneous Crohn’s disease; chronic idiopathic urticaria; dyshidrotic syndrome).
The pretreatment workup should include a CBC and biochemistry, liver and kidney function tests, and a pregnancy test if appropriate. When indicated, serology for hepatitis B and C viruses and human immunodeficiency virus should also be ordered. A baseline chest radiograph and Mantoux test are also recommended.
A CBC should be obtained 7 to 14 days after the initial test dose and every 3 months thereafter. Liver and kidney function should be assessed at baseline and every 3 months thereafter. In the presence of associated risk factors or changes from baseline results, more frequent monitoring of laboratory parameters may be necessary until the abnormalities are stable or have returned to normal.
Toxicities from folate antagonism, including anemia, neutropenia, stomatitis and oral ulcers can be prevented or alleviated by folate supplementation. Toxicities unrelated to suppression of folate metabolism include nodulosis, hepatic fibrosis, pulmonary fibrosis, lethargy, fatigue, and renal insufficiency.
Besides pregnancy and lactation, alcoholic liver disease or other chronic liver disease, immunodeficiency syndromes, bone-marrow hypoplasia (leukopenia, thrombocytopenia, or significant anemia) and hypersensitivity to methotrexate are now considered as absolute contraindications for methotrexate. While relative contraindications include abnormalities in renal and liver functions, active infection, obesity, diabetes mellitus, concomitant use of hepatotoxic drugs, recent vaccination with a live vaccine, and unreliable patient.
Retinoids influence the growth and differentiation of epidermal cells and interfere with sebaceous glands activity. Moreover, they have immunomodulator and anti-inflammatory properties. In the treatment of acne, they act on the primary lesion - the microcomedone - and aid in sebaceous suppression.
Intermittent isotretinoin may represent an effective alternative treatment, especially in moderate acne with a low incidence and severity of side effects. The intermittent isotretinoin can be recommended in those patients not tolerating the classical dosage.
Adverse effects of isotretinoin include teratogenicity, dry lips, nose and skin, facial dermatitis, conjunctivitis, hair loss, photosensitivity, depression and Elevated levels of lipids and liver enzymes. Pregnancy is an absolute contraindication.
The effect of IQ cream on immunity has suggested its possible use in the treatment of a wide variety of dermatologic conditions in which the immune system is thought to play a role in regression of the disease. IQ 5% cream is applied three times per week at bedtime. It’s used in external genital and perianal warts, molluscum contagiosum, AKs, BCC, Bowen’s disease.
Burning, pruritus, pain, tenderness, erythema, oedema, vesicles, erosions, ulcerations, excoriations, exudation and crusting are the most common adverse effects of IQ cream.
Intermittent or pulse therapy with topical 5-FU is applied only once or twice a week to treat AKs, NMSC and psoriasis. But it might cause erythema, irritation, burning, dryness, pain, pruritus and hypo- or hyperpigmentation. Allergic contact dermatitis has been reported. Systemic toxicity is rare.