practical management of the most common autoimmune bullous diseases.ppt

Practical Management of

the Most Common

Autoimmune

Bullous Diseases

By

Khalid M. Gharib

Corticosteroid is the most frequently used

agent in the treatment of Autoimmune

Bullous Diseases

CorticosteroidsCorticosteroids have anti-inflammatory and

immunosuppressive effects and their pharmacology is understood. It is important to monitor their various side effects,

both chronic and acute, which include adrenal insufficiency, electrolyte imbalances, hypertension, hyperglycemia, myopathy, immunosuppression, psychosis, cataracts, glaucoma, osteonecrosis and osteoporosis, infections, and gastrointestinal symptoms.

Actas Dermosifiliogr. 2008;99:441-55

Osteoporosis is monitored by :

yearly bone densitometry and controlled by administration of :

calcium(1,500 mg/d), vitamin D (400 IU/d), and bisphosphonates such as alendronate (Fosamax) (weekly tablets are available). ( selectively destroying macrophage and inhibiting their proinflammatory cytokines production).

The development of osteoporosis is related to the dose and the duration of therapy. It is estimated that in 30% to 50 % of patients on a long-term glucocorticoids regimen, fractures develop.


The mechanism by which glucocorticoids cause osteoporosis is believed to be a combination of a decrease in calcium absorption and suppression of new bone formation by osteoblasts

Prednisolone in Pemphigus Vulgaris

The starting dose is 1 mg/kg/d divided into 2 or 3 doses.

( A POINT OF DISSCUSSION)

Most patients obtain remission within 4 to 12 weeks.

The dose is maintained for 6 to 10 weeks,

Then decreased by 10 to 20 mg every 2 to 4 weeks.

(J Am Acad Dermatol 2004;51:859-77.)

When the dose is 40 mg daily, the schedule is changed to every other day.

HOW?

This transition is accomplished by keeping the first day’s dose at 40 mg

and decreasing the second day’s dose by 5 to 10 mg every 2 to 4 weeks.

When the patient is taking 40 mg every other day,

the dose is tapered by 5 mg every 2 to 4 week.


If there is no recurrence, the patient undergoes a maintenance regimen of 5 mg daily or every other day for several years.

( A POINT OF DISSCUSSION).

The administration of methylprednisolone, 1 g/d intravenously over 1 to 3 hours for a few (usually 3) consecutive days, is referred to as pulse steroid therapy


In Bullous PemphegoidThe dose is 1/2 to 3/4 mg/kg/d.Unlike the treatment of PV, higher doses of prednisone

are rarely needed. A clinical response is usually obtained within 1 to 4

weeks and is indicated by healing of existing lesions and cessation of new blister formation.

The prednisone dose is then gradually decreased by relatively large portions (10 mg) initially and smaller portions (2.5-5 mg) later.


When the daily dose is 30 to 40 mg, a shift to every other day is attempted to decrease the potential for long-term glucocorticoid side effects.

This shift is usually accomplished with a decrease in the second-day dose by 5 to 10 mg every 1 to 2 weeks.

Once the second day dose is nil, the first-day dose may be tapered slowly.

There are NO clear criteria regarding cure or remission.Some authors define them on the basis of indirect or

direct immunofluorescence, Others on the basis of symptoms or the requirement for

immunosuppressive therapy. One of the criteria used is the absence of lesions

for 3 months, but this is inconsistent with clinical experience with

these patients. (J Am Acad Dermatol 2004;51:859-77.)

Imuran)) AzathioprineThe most common steroid-sparing immunosuppressive

drug is azathioprine at a dose of 50 mg every 12 hours,The usual dose of azathioprine is 2.5 mg/kg/dBut it is best to adjust the dose according to the thiopurine

methytransferase enzyme that metabolizes the drug. Thiopurine methyltransferase deficiency (approximately 1

in 300 individuals). Patients with a high level of thiopurine methyltransferase may need 4 to 5 mg/ kg/d.


Treatment With Intravenous Cyclophosphamide(Genoxal)

1. Begin with oral cyclophosphamide at 50 mg every 12 hours and monitor tolerance by laboratory analysis

(suspend treatment if a white cell count < 2500 cells/mm3

is observed)

2. Intravenous treatment

a. Dose every 15-30 days

b. 1-1.5 g/m2; infusion in 200 mL over 2 hours

c. Hydration with saline (500 mL in 3 hours)

d. Cycles, 3 to 10 according to response3. Follow-up with complete blood count, urinalysis,

and monitoring of nausea/vomiting and infections Actas Dermosifiliogr. 2008;99:441-55

Dexamethasone-Cyclophosphamide Pulse Therapy

Phase 1:

Dexamethasone (100 mg dissolved in 500ml 5% dextrose) slow intravenous over 2h on 3consecutive days

+ cyclophosphamide 500 mg on day 1

DCP repeated every 4 w

Between these pulses : once daily oral cyclophosphamide 50 mg

Phase 2: Monthly pulse therapy of DCP for minimum

6 mPhase 3: stop monthly pulses but continue oral 50

mg for additional one yearPhase 4: withdrawn oral and follow up .

Dermatology online journal,2003

Oral cyclophosphamide for treatment ofpemphigus vulgaris and foliaceus

Patients received oral cyclophosphamide at a dose of 2 to 2.5 mg/kg/d each morning followed by aggressive oral hydration (hemorrhagic cystitis)with at least 2 to 3 L of fluids.

Prednisone (1 mg/kg/d) was also used, and tapering of the prednisone commenced after 2 to 3 months of therapy. Reductions of prednisone then occurred on a monthly basis, until a maintenance dose was achieved.

Patients with severe cutaneous disease (more than 40% body surface involvement), Once prednisone was reduced below 20 mg/d, the cyclophosphamide dose was adjusted to maintain an absolute neutrophil count of 1500 to 2500 c/L

If the absolute neutrophil count decreased below this target range, the cyclophosphamide was temporarily discontinued and restarted at a lower dose.

American academy of dermatology,2003

Azathioprine is less effective than cyclophosphamide

but appears to be more widely used.

It is less toxic and therefore requires less monitoring than cyclophosphamide.

Due to its relatively lower toxicity, lower risk of sterility, and lower lifetime risk of malignancy, it is indicated in younger persons.

Treatment With Rituximab (Mabthera)1. Prior to treatment Hepatitis C virus

serology Antibodies (indirect immunofluorescence,

enzyme- linked immunosorbent assay).

2. Dose, 375 mg/m2 (600-650 mg) a. One day a week b. Four weeks

c. Some use intravenous immunoglobulin 0.4 g/kg the day before (infection prophylaxis)

d. In case of relapse, a single dose according to clinical course

3. Premedicate with 1 ampule of dexchlorpheniramine and 1 g intravenous paracetamol 1 hour before

4. Slow infusion (6 hours) beginning at 15 mL/min for 15 minutes


Autoimmune bullous skin disorder intensity score

The severity of pemphigus can vary even within

individuals.

Efforts have been made to develop a scale for the measurement of severity similar to the Psoriasis

Area Severity Index,6 covering criteria such as : the rule of 9’s, the extent of erosion or dry

crust, and tolerated foods (the so-called autoimmune bullous skin

disorder intensity score), with good intentions but little practical use.

Severity is also classified as mild, moderate, and severe

according to the judgment of the observer. The disease continues to be associated with a

mortality of 5%, usually as a result of treatment complications.


The choice of therapy is dependent to some degree on the severity of the disease at presentation.

Other factors that play a role in choosing therapy are patient-related (age, general health, and associated medical illnesses such as diabetes, hypertension, or tuberculosis) and drug-related (onset of action, efficacy, adverse effects, and cost).

Unless there is an absolute contraindication, the initial therapy of PV is systemic glucocorticoid.

practical management of the most common autoimmune bullous diseases.ppt

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