Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

localised lesions in children or adults

1st line – topical corticosteroids or topical tacrolimus

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ACUTE
|
localised lesions in children or adults
1st line – 

topical corticosteroids or topical tacrolimus

Localised disease may be successfully managed with high-potency topical corticosteroids, with or without occlusion.[35][41]

Widespread application of potent topical corticosteroids (such as fluorinated corticosteroids) over a large body surface area may result in significant systemic absorption and should be avoided. Use of occlusion enhances the effect of the topical corticosteroid, but also increases absorption, so it should be limited to small body surface areas and only several days at a time.

Individual case reports described a response to topical treatment with tacrolimus, a calcineurin inhibitor. Topical tacrolimus causes more local irritation than topical corticosteroids, but it may be useful as an alternative in localised and limited disease without the disadvantage of causing skin atrophy.[38]

Primary options

clobetasol topical: (0.05%) apply sparingly to the affected area(s) twice daily for up to 2 weeks

Secondary options

tacrolimus topical: (0.1%) apply sparingly to the affected area(s) twice daily for up to 2 weeks

Consider – sedating antihistamines

Back
ACUTE
|
localised lesions in children or adults
Consider – 

sedating antihistamines

Additional treatment recommended for SOME patients in selected patient group

Itch is usually controlled with the use of oral sedating antihistamines, such as hydroxyzine or diphenhydramine.

Primary options

hydroxyzine: children ≤40 kg: 2 mg/kg/day orally given in divided doses every 6-8 hours when required ; children >40 kg and adults: 25 mg orally every 6-8 hours when required, maximum 100 mg/day

OR

diphenhydramine: children 2-6 years of age: 6.25 mg orally/intravenously/intramuscularly every 4-6 hours when required; children 6-12 years of age: 12.5 to 25 mg orally/intravenously/intramuscularly every 4-6 hours when required; adults: 25-50 mg orally/intravenously/intramuscularly every 4-6 hours when required

widespread lesions in adults

1st line – oral corticosteroids

Back
ACUTE
|
widespread lesions in adults
|
no contraindication to oral corticosteroids
1st line – 

oral corticosteroids

Most patients will respond well to systemic corticosteroids. However, it is essential to use systemic corticosteroids for the shortest duration and at the lowest dose possible, to avoid serious adverse effects. Starting doses of prednisolone >0.75 mg/kg/day may not give additional benefit. Lower doses may be adequate to control disease and reduce the incidence and severity of adverse reactions.[37] [ Cochrane Clinical Answers logo ]

The initial dose is maintained until cessation of new blister formation. It is then slowly tapered over 6 to 9 months.

Primary options

prednisolone: 0.5 to 2 mg/kg/day orally

Consider – sedating antihistamines

Back
ACUTE
|
widespread lesions in adults
|
no contraindication to oral corticosteroids
Consider – 

sedating antihistamines

Additional treatment recommended for SOME patients in selected patient group

Itch is usually controlled with the use of oral sedating antihistamines, such as hydroxyzine or diphenhydramine.

Primary options

hydroxyzine: 25 mg orally every 6-8 hours when required, maximum 100 mg/day

OR

diphenhydramine: 25-50 mg orally/intravenously/intramuscularly every 4-6 hours when required

2nd line – oral corticosteroids plus antibiotic therapy

Back
ACUTE
|
widespread lesions in adults
|
no contraindication to oral corticosteroids
2nd line – 

oral corticosteroids plus antibiotic therapy

Most patients will respond well to systemic corticosteroids. However, it is essential to use systemic corticosteroids for the shortest duration and at the lowest dose possible, to avoid serious adverse effects. The initial dose is maintained until cessation of new blister formation. It is then slowly tapered over 6 to 9 months.

The addition of antibiotics is considered for corticosteroid-sparing if long-term use is anticipated.[9][38]

If antibiotics such as tetracycline plus nicotinamide are added, corticosteroids may be tapered and stopped more rapidly (over several months).

Nicotinamide is used in combination with antibiotics and appears to have anti-inflammatory properties. It may act as a histamine receptor antagonist and has also has been reported to inhibit eosinophil and neutrophil chemotaxis and secretion.[39] Nicotinamide lacks the vasodilator, gastrointestinal, hepatic, and hypolipaemic actions of nicotinic acid. As such, nicotinamide has not been shown to produce the flushing, itching, and burning sensations of the skin as is commonly seen when large doses of nicotinic acid are given orally.[40]

On successful treatment of blisters, the antibiotics and nicotinamide should be slowly tapered over several months to avoid a relapse.[38]

Primary options

prednisolone: 0.5 to 2 mg/kg/day orally

-- AND --

nicotinamide: 500-2000 mg orally once daily at bedtime

-- AND --

tetracycline: 250-500 mg orally four times daily

or

doxycycline: 50-100 mg orally once or twice daily

or

minocycline: 50-100 mg orally once or twice daily

or

erythromycin base: 333 mg orally (delayed-release) three times daily

Consider – ciclosporin

Back
ACUTE
|
widespread lesions in adults
|
no contraindication to oral corticosteroids
Consider – 

ciclosporin

Additional treatment recommended for SOME patients in selected patient group

Ciclosporin can be added to the combination therapy as a corticosteroid-sparing drug; the systemic corticosteroids would then be slowly tapered over weeks to months while the patient continues taking antibiotics. A slow corticosteroid taper depends on the patient's starting dose and duration of therapy, and is adjusted to the clinical response of the patient once the disease process is stable.

The evidence for benefit with ciclosporin is conflicting, even with relatively high doses of >6 mg/kg/day, and responses mainly occurred in patients treated with concomitant oral corticosteroids.[37]

Primary options

ciclosporin: 2.5 to 4 mg/kg/day orally given in 2 divided doses

More

Consider – sedating antihistamines

Back
ACUTE
|
widespread lesions in adults
|
no contraindication to oral corticosteroids
Consider – 

sedating antihistamines

Additional treatment recommended for SOME patients in selected patient group

Itch is usually controlled with the use of oral sedating antihistamines, such as hydroxyzine or diphenhydramine.

Primary options

hydroxyzine: 25 mg orally every 6-8 hours when required, maximum 100 mg/day

OR

diphenhydramine: 25-50 mg orally/intravenously/intramuscularly every 4-6 hours when required

1st line – dapsone or antibiotic therapy or immunosuppressants

Back
ACUTE
|
widespread lesions in adults
|
contraindication to corticosteroids
1st line – 

dapsone or antibiotic therapy or immunosuppressants

If corticosteroid treatment is contraindicated for those with systemic lesions, alternative treatments exist.[30]

Dapsone is used, especially if patients have a neutrophil-rich infiltrate. It is contraindicated in glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD deficiency predisposes to haematological adverse effects of dapsone and should be excluded in predisposed races.[38] In the US, black males are most commonly affected, with a prevalence of approximately 10%.

Other options are a combination of tetracycline and nicotinamide, and immunosuppressive drugs.

Nicotinamide is used in combination with antibiotics and appears to have anti-inflammatory properties. It may act as a histamine receptor antagonist and has also has been reported to inhibit eosinophil and neutrophil chemotaxis and secretion.[39] Nicotinamide lacks the vasodilator, gastrointestinal, hepatic, and hypolipaemic actions of nicotinic acid. As such, nicotinamide has not been shown to produce the flushing, itching, and burning sensations of the skin as is commonly seen when large doses of nicotinic acid are given orally.[40]

On successful treatment of blisters, the antibiotics and nicotinamide should be slowly tapered over several months to avoid a relapse.[38]

Methotrexate is considered in patients with concomitant psoriasis and bullous pemphigoid in the hands of practitioners with experience using antimetabolites. Methotrexate should include folic acid or calcium folinate as part of the regimen.

Primary options

dapsone: 50 mg orally once daily

OR

nicotinamide: 500-2000 mg orally once daily at bedtime

-- AND --

tetracycline: 250-500 mg orally four times daily

or

doxycycline: 50-100 mg orally once or twice daily

or

minocycline: 50-100 mg orally once or twice daily

or

erythromycin base: 333 mg orally (delayed-release) three times daily

OR

methotrexate: 7.5 mg orally/intramuscularly once weekly on the same day of each week initially, increase gradually according to response, maximum 25 mg/week; or 2.5 to 7.5 mg orally every 12 hours for 3 doses per week; use lowest effective dose

-- AND --

folic acid: 1 mg orally once daily (except on day when methotrexate is given)

or

calcium folinate: 5 mg orally once weekly (on a different day to when methotrexate is given)

OR

azathioprine: 50-200 mg orally once daily, adjust according to response, maximum 2.5 mg/kg/day

OR

mycophenolate mofetil: 500-1000 mg orally twice daily

OR

chlorambucil: 6 mg orally once daily

OR

cyclophosphamide: 2-3 mg/kg/day orally

Consider – sedating antihistamines

Back
ACUTE
|
widespread lesions in adults
|
contraindication to corticosteroids
Consider – 

sedating antihistamines

Additional treatment recommended for SOME patients in selected patient group

Itch is usually controlled with the use of oral sedating antihistamines, such as hydroxyzine or diphenhydramine.

Primary options

hydroxyzine: 25 mg orally every 6-8 hours when required, maximum 100 mg/day

OR

diphenhydramine: 25-50 mg orally/intravenously/intramuscularly every 4-6 hours when required

1st line – prednisolone plus immunosuppressant or immunosuppressant alone

Back
ACUTE
|
widespread lesions in adults
|
inadequate response to initial therapy
1st line – 

prednisolone plus immunosuppressant or immunosuppressant alone

If the patient requires high doses of systemic corticosteroids for maintenance or is not showing a clinical response, other immunosuppressive (corticosteroid-sparing) agents, such as azathioprine, mycophenolate, or ciclosporin, may be added.

Other therapies for severe generalised disease include cyclophosphamide and methotrexate.[35]

The initial dose of prednisolone is maintained until new blister formation ceases. It is then slowly tapered over 6 to 9 months.

Methotrexate is considered in patients with concomitant psoriasis and bullous pemphigoid in the hands of practitioners with experience using antimetabolites. Methotrexate should include folic acid or calcium folinate as part of the regimen.

There is currently insufficient evidence to recommend routine addition of azathioprine to systemic corticosteroids. Because of its side effects, azathioprine should be considered as an adjunctive treatment to prednisolone only when response has been inadequate and the disease is not suppressed, or where the side effects of existing therapy are unacceptable.[38]

The evidence for benefit with ciclosporin is conflicting, even with relatively high doses of >6 mg/kg/day, and responses mainly occurred in patients treated with concomitant oral corticosteroids.[37]

Primary options

prednisolone: 0.5 to 1 mg/kg/day orally

-- AND --

azathioprine: 50-200 mg orally once daily, adjust according to response, maximum 2.5 mg/kg/day

or

mycophenolate mofetil: 500-1000 mg orally twice daily

or

ciclosporin: 2.5 to 4 mg/kg/day orally given in 2 divided doses

More

OR

cyclophosphamide: 2-3 mg/kg/day orally

OR

methotrexate: 7.5 mg orally/intramuscularly once weekly on the same day of each week initially, increase gradually according to response, maximum 25 mg/week; or 2.5 to 7.5 mg orally every 12 hours for 3 doses per week; use lowest effective dose

-- AND --

folic acid: 1 mg orally once daily (except on day when methotrexate is given)

or

calcium folinate: 5 mg orally once weekly (on a different day to when methotrexate is given)

Consider – sedating antihistamines

Back
ACUTE
|
widespread lesions in adults
|
inadequate response to initial therapy
Consider – 

sedating antihistamines

Additional treatment recommended for SOME patients in selected patient group

Itch is usually controlled with the use of oral sedating antihistamines, such as hydroxyzine or diphenhydramine.

Primary options

hydroxyzine: 25 mg orally every 6-8 hours when required, maximum 100 mg/day

OR

diphenhydramine: 25-50 mg orally/intravenously/intramuscularly every 4-6 hours when required

2nd line – plasmapheresis or intravenous immunoglobulin (IVIG) and/or rituximab

Back
ACUTE
|
widespread lesions in adults
|
inadequate response to initial therapy
2nd line – 

plasmapheresis or intravenous immunoglobulin (IVIG) and/or rituximab

Plasmapheresis or IVIG and/or rituximab are used if all other treatment options fail.

The total published experience of IVIG in bullous pemphigoid is very small and suggests that it is of limited value. It produced some dramatic but short-lived responses.[43]

Rituximab alone or the combination of rituximab and intravenous immunoglobulin or immuno-adsorption appears to be advantageous in severe cases.[45][46][47][48]

Primary options

plasmapheresis

OR

normal immunoglobulin human: 400 mg/kg/day intravenously for 5 days

and/or

rituximab: consult specialist for guidance on dose

Consider – sedating antihistamines

Back
ACUTE
|
widespread lesions in adults
|
inadequate response to initial therapy
Consider – 

sedating antihistamines

Additional treatment recommended for SOME patients in selected patient group

Itch is usually controlled with the use of oral sedating antihistamines, such as hydroxyzine or diphenhydramine.

Primary options

hydroxyzine: 25 mg orally every 6-8 hours when required, maximum 100 mg/day

OR

diphenhydramine: 25-50 mg orally/intravenously/intramuscularly every 4-6 hours when required

widespread lesions in children

1st line – oral corticosteroids

Back
ACUTE
|
widespread lesions in children
|
no contraindication to oral corticosteroids
1st line – 

oral corticosteroids

Most patients will respond well to systemic corticosteroids. However, it is essential to use systemic corticosteroids for the shortest duration and at the lowest dose possible, to avoid serious adverse effects.

The initial dose is maintained until new blister formation ceases. It is then slowly tapered over 6 to 9 months.

Primary options

prednisolone: 0.5 to 2 mg/kg/day orally

Consider – sedating antihistamines

Back
ACUTE
|
widespread lesions in children
|
no contraindication to oral corticosteroids
Consider – 

sedating antihistamines

Additional treatment recommended for SOME patients in selected patient group

Itch is usually controlled with the use of oral sedating antihistamines, such as hydroxyzine or diphenhydramine.

Primary options

hydroxyzine: children ≤40 kg: 2 mg/kg/day orally given in divided doses every 6-8 hours when required ; children >40 kg: 25 mg orally every 6-8 hours when required, maximum 100 mg/day

OR

diphenhydramine: children 2-6 years of age: 6.25 mg orally/intravenously/intramuscularly every 4-6 hours when required; children 6-12 years of age: 12.5 to 25 mg orally/intravenously/intramuscularly every 4-6 hours when required

2nd line – oral corticosteroids plus antibiotic therapy

Back
ACUTE
|
widespread lesions in children
|
no contraindication to oral corticosteroids
2nd line – 

oral corticosteroids plus antibiotic therapy

Most patients will respond well to systemic corticosteroids. However, it is essential to use systemic corticosteroids for the shortest duration and at the lowest dose possible, to avoid serious adverse effects. The initial dose is maintained until new blister formation ceases. It is then slowly tapered over 6 to 9 months.

The addition of antibiotics is considered for corticosteroid-sparing if long-term use is anticipated.[9][38] If antibiotics such as tetracycline plus nicotinamide are added, corticosteroids may be tapered and stopped more rapidly (over several months).

Nicotinamide is used in combination with antibiotics and appears to have anti-inflammatory properties. It may act as a histamine receptor antagonist and has also has been reported to inhibit eosinophil and neutrophil chemotaxis and secretion.[39] Nicotinamide lacks the vasodilator, gastrointestinal, hepatic, and hypolipaemic actions of nicotinic acid. As such, nicotinamide has not been shown to produce the flushing, itching, and burning sensations of the skin as is commonly seen when large doses of nicotinic acid are given orally.[40]

On successful treatment of blisters, the antibiotics and nicotinamide should be slowly tapered over several months to avoid a relapse.[38]

Primary options

prednisolone: 0.5 to 2 mg/kg/day orally

and

erythromycin base: 30-50 mg/kg/day orally given in divided doses every 6-8 hours

and

nicotinamide: 500-2000 mg orally once daily at bedtime

Consider – ciclosporin

Back
ACUTE
|
widespread lesions in children
|
no contraindication to oral corticosteroids
Consider – 

ciclosporin

Additional treatment recommended for SOME patients in selected patient group

In children, there are reports of success with ciclosporin in the more resistant cases. Ciclosporin can be added to the combination therapy as a corticosteroid-sparing drug; the systemic corticosteroids would then be slowly tapered over weeks to months while the patient continues taking antibiotics. A slow corticosteroid taper depends on the patient's starting dose and duration of therapy, and is adjusted to the clinical response of the patient once the disease process is stable.

The evidence for benefit with ciclosporin is conflicting, even with relatively high doses of >6 mg/kg/day, and responses mainly occurred in patients treated with concomitant oral corticosteroids.[37]

Primary options

ciclosporin: 2.5 to 4 mg/kg/day orally given in 2 divided doses

More

Consider – sedating antihistamines

Back
ACUTE
|
widespread lesions in children
|
no contraindication to oral corticosteroids
Consider – 

sedating antihistamines

Additional treatment recommended for SOME patients in selected patient group

Itch is usually controlled with the use of oral sedating antihistamines, such as hydroxyzine or diphenhydramine.

Primary options

hydroxyzine: children ≤40 kg: 2 mg/kg/day orally given in divided doses every 6-8 hours when required ; children >40 kg: 25 mg orally every 6-8 hours when required, maximum 100 mg/day

OR

diphenhydramine: children 2-6 years of age: 6.25 mg orally/intravenously/intramuscularly every 4-6 hours when required; children 6-12 years of age: 12.5 to 25 mg orally/intravenously/intramuscularly every 4-6 hours when required

1st line – antibiotic therapy or dapsone

Back
ACUTE
|
widespread lesions in children
|
contraindication to corticosteroids and time-limited disease
1st line – 

antibiotic therapy or dapsone

Children who have contraindications for corticosteroid therapy are often treated initially with erythromycin and niacin or dapsone.

Dapsone is used, especially if patients have a neutrophil-rich infiltrate. It is contraindicated in glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD deficiency predisposes to haematological adverse effects of dapsone and should be excluded in predisposed races.[38] In the US, black males are most commonly affected, with a prevalence of approximately 10%.

Other options are a combination of tetracycline and nicotinamide, and immunosuppressive drugs.

Nicotinamide is used in combination with antibiotics and appears to have anti-inflammatory properties. It may act as a histamine receptor antagonist and has also has been reported to inhibit eosinophil and neutrophil chemotaxis and secretion.[39] Nicotinamide lacks the vasodilator, gastrointestinal, hepatic, and hypolipaemic actions of nicotinic acid. As such, nicotinamide has not been shown to produce the flushing, itching, and burning sensations of the skin as is commonly seen when large doses of nicotinic acid are given orally.[40]

On successful treatment of blisters, the antibiotics and nicotinamide should be slowly tapered over several months to avoid a relapse.[38]

Primary options

nicotinamide: 500-2000 mg orally once daily at bedtime

and

erythromycin base: 30-50 mg/kg/day orally given in divided doses every 6-8 hours

OR

dapsone: 2 mg/kg/day orally

Consider – sedating antihistamines

Back
ACUTE
|
widespread lesions in children
|
contraindication to corticosteroids and time-limited disease
Consider – 

sedating antihistamines

Additional treatment recommended for SOME patients in selected patient group

Itch is usually controlled with the use of oral sedating antihistamines, such as hydroxyzine or diphenhydramine.

Primary options

hydroxyzine: children ≤40 kg: 2 mg/kg/day orally given in divided doses every 6-8 hours when required ; children >40 kg: 25 mg orally every 6-8 hours when required, maximum 100 mg/day

OR

diphenhydramine: children 2-6 years of age: 6.25 mg orally/intravenously/intramuscularly every 4-6 hours when required; children 6-12 years of age: 12.5 to 25 mg orally/intravenously/intramuscularly every 4-6 hours when required

1st line – dapsone or chlorambucil or high-dose intravenous methylprednisolone

Back
ACUTE
|
widespread lesions in children
|
inadequate response to initial therapy
1st line – 

dapsone or chlorambucil or high-dose intravenous methylprednisolone

In children, there are reports of success with dapsone and chlorambucil in the more resistant cases. Note that dapsone is contraindicated in glucose-6-phosphate dehydrogenase (G6PD) deficiency. High-dose intravenous methylprednisolone therapy has also been shown effective. In most, remission is achieved within the first year.

Primary options

dapsone: 2 mg/kg/day orally

OR

chlorambucil: consult specialist for guidance on dose

OR

methylprednisolone: 4-48 mg/day intravenously given in 4 divided doses

Consider – sedating antihistamines

Back
ACUTE
|
widespread lesions in children
|
inadequate response to initial therapy
Consider – 

sedating antihistamines

Additional treatment recommended for SOME patients in selected patient group

Itch is usually controlled with the use of oral sedating antihistamines, such as hydroxyzine or diphenhydramine.

Primary options

hydroxyzine: children ≤40 kg: 2 mg/kg/day orally given in divided doses every 6-8 hours when required ; children >40 kg: 25 mg orally every 6-8 hours when required, maximum 100 mg/day

OR

diphenhydramine: children 2-6 years of age: 6.25 mg orally/intravenously/intramuscularly every 4-6 hours when required; children 6-12 years of age: 12.5 to 25 mg orally/intravenously/intramuscularly every 4-6 hours when required

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Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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