Download MBBS Dermatology PPT 30 Systemic Steroids And Pulse Therapy Lecture Notes

Download MBBS (Bachelor of Medicine, Bachelor of Surgery) Dermatology PPT 30 Systemic Steroids And Pulse Therapy Lecture Notes

Systemic steroids and Pulse

therapy in Dermatology

Thursday, March 24, 2022

Systemic glucocorticoids

? Potent immunosuppressive and anti-inflammatory agents
? Knowledge of basic pharmacology - essential to maximize their

efficacy and safety as therapeutic agents
? Major naturally occurring glucocorticoid ? Cortisol (hydrocortisone)
? Synthesized from cholesterol by the adrenal cortex
? Normally, <5% of circulating cortisol is unbound the active

therapeutic form

? Remainder - inactive

Mechanism of glucocorticoids action

? Passive diffusion of the glucocorticoids through the cell membrane
? F/b binding to soluble receptor proteins in the cytoplasm
? The hormone-receptor complex then moves to the nucleus
? Regulates the transcription of its target genes
Cellular effects of glucocorticoids

? Affect the replication and movement of cells
? Induce monocytopenia, eosinopenia, and lymphocytopenia
? Lymphocytopenia - a redistribution of cells - migration from the

circulation to other lymphoid tissues

? Increase in circulating PMN leukocytes - movement of cells from the

bone marrow, diminished rate of removal from circulation and

possibly inhibition of neutrophil apoptosis

? Macrophage functions, including phagocytosis, antigen processing

and cell killing - decreased by cortisol

? This affects immediate and delayed hypersensitivity
? Granulomatous infectious diseases (e.g. tuberculosis) - prone to

exacerbation/ relapse during prolonged glucocorticoid therapy

? Antibody-forming cells, B lymphocytes and plasma cells - relatively

resistant to effects of glucocorticoids


Short courses of glucocorticoids

Have been used for
? Severe dermatitis
? Contact dermatitis
? Atopic dermatitis
? Photodermatitis
? Exfoliative dermatitis & Erythrodermas


Fundamental principles of glucocorticoids therapy

? Before glucocorticoids therapy with is begun - the benefit
? Alternative/ adjunctive therapies (azathioprine, cyclophosphamide)
? Especially if long term treatment
? Coexisting illnesses such as diabetes, hypertension and osteoporosis

need consideration
Diet during glucocorticoids therapy

? Low in calories, fat and sodium
? High in protein, potassium and calcium as tolerated
? Also consider associated comorbidities
? Protein intake - to reduce steroid-induced nitrogen/ muscle wasting
? Minimize alcohol, coffee and nicotine/ smoking
? Encourage exercise

? Basic preventative measures ? to be followed

Potential adverse effects

? A plethora of variety of side effects, when used in high

(supraphysiological) doses and in long term regimens

? Short courses (2?3 weeks) of GCs relatively safe
Side effects due to mineralocorticoids action

? Hypernatraemia and water retention
? Hypertension and weight gain
? Hypokalaemia, hypocalcaemia

Side effects due to glucocorticoids action

? Hyperglycaemia, development of diabetes
? Deterioration of diabetic control
? Dyslipidaemia ? hypertriglyceridaemia, hypercholesterolaemia
? Increased appetite, weight gain
? Menstrual irregularities
? Cushingoid features (lipodystrophy) ? moon face, `buffalo hump',

central obesity (thin limbs, plump trunk)
Cutaneous side effects

? Purpura, bruising, striae, dermal and epidermal atrophy,

telangiectasia

? `Steroid acne', rosacealike syndrome
? Impaired wound healing
? Hirsutism
? Fat atrophy with injected GCs
? Cutaneous infections ? staphylococcal and herpetic
? Hyperhidrosis

? Osteoporosis.

?Osteonecrosis (avascular necrosis).

? Growth impairment in children.

? Gastrointestinal

?Peptic ulceration.

?Bowel perforation (particular risk with active diverticulitis and

recent bowel anastomosis).

?Pancreatitis.

?Fatty liver.

?Gastrooesophageal reflux.

?Candidiasis.
? Psychiatric - occur in approximately 6% of patients
?Psychosis.
?Euphoria, depression, agitation.
?Suicidal ideation.
?Insomnia, nightmares.
?Irritability, mood lability.

? Ocular
?Ocular hypertension and glaucoma.
?Cataracts ? posterior subcapsular.
?Central serous chorioretinopathy.
?Ocular infections, including herpes simplex.

? Neuromuscular
? Muscle weakness (proximal myopathy).
?Intracranial hypertension (pseudotumor cerebri).
?Spinal epidural lipomatosis.
? Infections
?Tuberculosis reactivation.
?Opportunistic infections (consider Pneumocystis jiroveci pneumonia

prophylaxis)

? Prior to initiating GC therapy
? The patient and family members provided adequate counselling
? Information about the potential adverse effects
? A steroid treatment card - to be provided
Dosage regimens

? Oral administration - Depends on:
?Clinical diagnosis
?Severity
?Presence of other factors
? Prednisolone (or equivalent) at a starting dose of up to 1 mg/kg bw/d,

ideally given as a single morning dose

? Less likely to cause adverse effects
? Less likely to result in HPA axis suppression

Pulse therapy

? Oral
? IV Pulse therapy (DCP, DP, methylprednisolone)
? Administration of supra-pharmacologic doses of drugs in an

intermittent manner - "pulse therapy"

? In pemphigus, pulse therapy refers to intravenous (IV) infusion of high

doses of steroids for quicker, better efficacy and to decrease the side

effects of long-term steroids
? Feduska et al. first used pulse therapy in 1972 for reversal of renal

allograft rejection

? In India, JS Pasricha & Ramji Gupta, 1984

Oral minipulse therapy (OMP)

? Corticosteroids therapy i.e., dexamethasone/betamethasone
? On 2 consecutive days in a week
? Can be continued for up to 3-6 months
? MC Indications ? vitiligo, alopecia areata
DCP / DP Pulse therapy

? DCP
? DP
? Methylprednisolone - also used

? Most common indication - Pemphigus

Medications

? Dexamethasone (100 mg) ? economic option
? or methylprednisolone (20-30 mg/kg)
? With cyclophosphamide 500 mg on 2nd day of pulse


Steps of pulse therapy

Phases of pulse therapy
Modifications

? Dexamethasoneazathioprine pulse (DAP):
? Cyclophosphamide is replaced by daily oral azathioprine.
? No bolus dose of azathioprine is given during the pulse
? DAP is recommended for unmarried patients
? Who have not completed their family (Cyclophosphamide not given-

gonadal failure at a cumulative dose of 30 g and 12 g in women and

men)

Common side effects

? Mood and behavior alteration, hyperactivity, psychosis, disorientation

and sleep disturbances - 10% patients

? Hyperglycemia, hypokalemia
? Infections
? Hiccups, facial flushing, diarrhea, weakness,
? Generalized swelling, myalgia
? Arrhythmias and shock