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eMedicine Specialties > Dermatology > Bullous Diseases

Bullous Pemphigoid: Treatment &

MedicationAuthor: Lawrence S Chan, MD, Dr Orville J Stone Professor of Dermatology, Head, Department of Dermatology,

University of Illinois College of Medicine

Contributor Information and Disclosures

Updated: May 28, 2010

TREATMENTMedical Care

As in other autoimmune bullous diseases, the goal of therapy is to decrease

blister formation, to promote healing of blisters and erosions, and to determine the

minimal dose of medication necessary to control the disease process. Therapy must

be individualized for each patient, keeping in mind preexisting conditions and other

patient-specific factors.

Consultations

Treatment of patients with bullous pemphigoid requires coordination of care

between the dermatologist and the patient's primary care provider. Patients with oral

disease may require an otolaryngologist and/or a dentist for evaluation and care. An

ophthalmologist should evaluate patients with suspected ocular involvement and

those requiring prolonged high-dose steroids.

Diet

The lesions may flare in patients with oral disease after eating hard and crunchyfoods, such as chips, raw fruits, and vegetables.

For patients treated with systemic corticosteroid for longer than 1 month, a

combined supplement of calcium and vitamin D should be instituted to prevent

osteoporosis. The dosage and the frequency are stated in the recommendations

established by the American College of Rheumatology Task Force in 1996.42

In addition to calcium and vitamin D supplementation, patients on long-term

treatment with systemic corticosteroids should be taking bisphosphonate, a specific

inhibitor for osteoclast-mediated bone resorption (eg, alendronate).

ActivityPatients should be instructed to avoid direct physical trauma to their skin

surfaces. For example, localized bullous pemphigoid has rarely been described

peristomally.
http://emedicine.medscape.com/specialtieshttp://emedicine.medscape.com/dermatologyhttp://emedicine.medscape.com/dermatology#bulloushttp://emedicine.medscape.com/dermatologyhttp://emedicine.medscape.com/dermatology#bulloushttp://emedicine.medscape.com/specialties


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MEDICATIONTreatment is directed at reducing the inflammatory response and autoantibody

production. Although target-specific therapy is the "Holy Grail" for

immunodermatologists, nontarget-specific treatments are currently used. The most

commonly used medications are anti-inflammatory agents (eg, corticosteroids,

tetracyclines, dapsone) and immunosuppressants (eg, azathioprine, methotrexate,

mycophenolate mofetil, cyclophosphamide). An article from Europe provided evidence

that strong topical corticosteroid treatment may achieve disease control while

avoiding systemic adverse effects from systemic corticosteroids.43

Proper treatments of bullous pemphigoid depend on the severity of the disease.

For localized disease, topical steroids plus the systemic anti-inflammatory (tetracycline

and nicotinamide) may be sufficient. Effects of monotherapy with nicotinamide are

unknown. For more severe cases, systemic steroids along with immunosuppressives

may be needed to control the disease. If the disease is difficult to control, consider

treatment with an anti-CD20 antibody (rituximab), which is relatively specific intargeting the antibody-producing B cells.44,45,46,47,48,49

Anti-inflammatory agents

These agents inhibit the inflammatory process by inhibiting specific cytokine

production and vascular permeability. They may also stabilize granulocyte membranes

and prevent release of key enzymes.

Prednisone (Deltasone)

May decrease inflammation by reversing increased capillary permeability and

suppressing PMN activity. When taken orally, it is used alone or in conjunction withother immunosuppressive agents for treating bullous pemphigoid.

Dosing

Adult

1 mg/kg/d not to exceed 80 mg/d; taper as symptoms resolve

Pediatric

Administer as in adults (consult patient's pediatrician before prescribing

medication)

Interactions

Increased levels occur with ketoconazole, erythromycin, clarithromycin,estrogens, and birth control pills; decreased levels occur with

aminoglutethimide, phenytoin, phenobarbital, rifampin, cholestyramine, and

ephedrine; levels of potassium-depleting diuretics (potentiates potassium loss

and digitalis toxicity) and cyclosporine increase; levels of isoniazid, insulin

(resistance is induced), and salicylates decrease; monitor anticoagulant therapy

and theophylline levels.

Contraindications

Absolute: Systemic fungal infection, herpes simplex keratitis, hypersensitivity

(usually with corticotropin, occasionally with IV forms)Relative: Hypertension, active TB, CHF, prior psychosis, positive purified protein

derivative test result, glaucoma, severe depression, diabetes mellitus, active


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peptic ulcer disease, cataracts, osteoporosis, recent bowel anastomosis,

pregnancy


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Precautions

Use lower dose in hypothyroidism, liver disease, and obesity (decreased

cortisol-binding globulin [CBG] and increased free fraction of steroid);

pregnancy, hyperthyroidism, and concurrent estrogen therapy may increase

CBG levels; abrupt discontinuation of glucocorticoids may cause adrenal crisis;

hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease,

hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growthsuppression, and infections may occur with glucocorticoid use; alternate-day

therapy does not prevent bone loss (appropriate monitoring and prophylaxis for

osteoporosis continues to evolve)

Tetracycline (Sumycin)

Although an antibiotic, tetracycline has proven effective in some cases of bullous

pemphigoid either alone or in conjunction with niacinamide (2 g/d). Efficacy may be

due to anti-inflammatory properties.

Dosing

Adult500 mg qid

Pediatric

8 years: 25-50 mg/kg/d (10-20 mg/lb)

Interactions

Bioavailability decreases with antacids containing aluminum, calcium,

magnesium, iron, or bismuth subsalicylate; can decrease effects of oral

contraceptives, causing breakthrough bleeding and increased risk of pregnancy;

can increase hypoprothrombinemic effects of anticoagulants.

Contraindications : Documented hypersensitivity; severe hepatic dysfunction

Precautions

Photosensitivity may occur with prolonged exposure to sunlight or tanning

equipment; reduce dose in renal impairment; consider drug serum level

determinations in prolonged therapy; use during tooth development (last one

half of pregnancy through age 8 y) can cause permanent discoloration of teeth;

Fanconilike syndrome may occur with outdated tetracyclines.

Clobetasol (Temovate)

Class I superpotent topical steroid; suppresses mitosis and increases synthesis of

proteins that decrease inflammation and cause vasoconstriction. Useful in treating

localized bullous pemphigoid or in conjunction with low-dose systemic corticosteroids

to treat the generalized disease.

Dosing

Adult

Apply bid for up to 2 wk; not to exceed 50 g/wk

Pediatric

12 years: Apply as in adults

Contraindications : Documented hypersensitivity; viral or fungal skin infections


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Precautions

Do not apply to face or intertriginous areas; systemic absorption and adrenal

suppression may occur with prolonged therapy or application to large surface

areas; may cause skin to atrophy; may increase risk of infections

Immunosuppressive agents

For patients in whom steroids or other anti-inflammatory agents have not caused aresponse or for those unable to tolerate prednisone, immunosuppressants are useful

adjuvants.

Azathioprine (Imuran)

Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May

decrease proliferation of lymphocytes. For use alone or in conjunction with prednisone.

Dosing

Adult

1 mg/kg qd/bid (empiric) or by TPMT level; increase by 0.5 mg/kg q4wk until

response, not to exceed 2.5 mg/kg/d.TPMT testing not entirely reliable; involves testing activity of TPMT activity in

RBCs, which correlates with systemic TPMT activity; functional enzyme test has

been shown to have variability between test sites, and kits may contain varying

amounts of enzyme inhibitor; starting at low doses, monitoring for

pancytopenia, then increasing the dose is an alternative; if clinical response is

not good, patient may be a homozygote for high activity and may need

increased dose; some references recommend checking before treatment in all

patients.

TPMT 19 U: Not to exceed 2.5 mg/kg

Pediatric

Safety and efficacy not established

Interactions

Allopurinol increases risk of pancytopenia; captopril/ACE inhibitors may increase

risk of anemia and leukopenia; warfarin dose may need to be increased;

pancuronium dose may need to be increased for adequate paralysis; live virus

vaccines and cotrimoxazole increase risk of hematologic toxicity; rifampicinmay cause transplants to possibly be rejected; clozapine may increase risk of

agranulocytosis.

Contraindications

Absolute: Documented hypersensitivity, pregnancy or attempting pregnancy,

clinically significant active infection

Relative: Concurrent use of allopurinol; prior treatment with alkylating agents

(eg, cyclophosphamide, chlorambucil, melphalan, others [high risk of

neoplasia])

Precautions


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Increased risk of neoplasia; caution in liver disease and renal impairment;

hematologic toxicities may occur; rarely, patients may develop fever without

associated infections; measure thiopurine methyltransferase level prior to

treatment; periodically monitor CBC count and liver function

Biologicals

Rituximab (Rituxan)Genetically engineered chimeric murine/human monoclonal antibody against human

CD20, a molecule present in normal and malignant B lymphocytes. Described in case

reports as a promising biological treatment for B-lymphocytemediated diseases (eg,

pemphigus vulgaris).

Dosing

Adult

Not approved by FDA for use in bullous pemphigoid; patients with other B-

lymphocytemediated disease (eg, non-Hodgkin lymphoma) used initial dose of

375 mg/m2 IV qwk for 4-8 wk

PediatricNot established

Interactions

Coadministration with cisplatin known to cause severe renal toxicity, including

acute renal failure; may interfere with immune response to live virus vaccine

(MMR) and reduce efficacy (do not administer within 3 mo of vaccine);

abciximab, antihypertensives, echinacea.

Contraindications

Documented hypersensitivity; documented anaphylaxis or IgE-mediatedhypersensitivity reaction to murine proteins or their components.

Precautions

Monitor CBC and platelet counts regularly during and few months

posttreatment for occurrence of cytopenia; monitor human antichimeric

antibody development (approximately 1% patients); monitor and treat

associated infections (30% probability).

Severe infusion reactions have occurred, typically during the first

infusion, with time to onset of 30-120 minutes; signs and symptoms may

include urticaria, hypotension, angioedema, hypoxia, or bronchospasm and may

require interruption of infusion; the most severe manifestations and sequelae

include pulmonary infiltrates, acute respiratory distress syndrome, myocardial

infarction, ventricular fibrillation, cardiogenic shock, and anaphylactic and

anaphylactoid events.

Factors most commonly associated with fatal outcomes are female sex,

pulmonary infiltrates, and chronic lymphocytic leukemia or mantle cell

lymphoma; infusions should be interrupted for severe reactions and medication

and supportive care measures provided; in most cases, the infusion can be

resumed at a 50% reduction in rate when symptoms have completely resolved.

Tumor lysis syndrome (TLS): Rapid reduction in tumor volume followed byacute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or

hyperphosphatemia has been reported within 12-24 h after the first infusion;


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risk greater in patients with high numbers of circulating malignant cells

(>25,000/ L) or high tumor burden; following complete resolution of TLS

complications, rituximab has been tolerated when re-administered in

conjunction with prophylactic therapy for TLS

Hepatitis B virus (HBV): Reactivation with related fulminant hepatitis and

other viral infections.


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HBV reactivation with related fulminant hepatitis, hepatic failure and

death have been reported in some patients with hematologic malignancies;

most patients received rituximab in combination with chemotherapy; median

time to diagnosis of hepatitis was approximately 4 mo after initiation of

rituximab and approximately 1 mo after last dose; patients who develop viral

hepatitis should have rituximab and any concomitant chemotherapy

discontinued; appropriate treatment should be initiated; data regarding safetyof resuming rituximab in patients who develop hepatitis subsequent to HBV

reactivation is insufficient

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