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 variant (classic annular rash)

1st line – conservative management

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ACUTE
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localised variant (classic annular rash)
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without cosmetic concerns
1st line – 

conservative management

Localised GA is usually left alone unless the patient insists on treatment for cosmetic reasons.

1st line – cryotherapy

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ACUTE
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localised variant (classic annular rash)
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with cosmetic concerns
1st line – 

cryotherapy

Cryotherapy with liquid nitrogen held approximately 10 cm from the lesion and at an angle of 45°. Two 5-second pulsed cycles should be used, and treatment areas should not overlap to minimise risk of atrophic scarring.

The patient may experience a stinging sensation, and the area may become inflamed immediately after therapy. Over the next week a scab or blister may form; these usually resolve in 7 days.

1st line – topical or intralesional corticosteroids

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ACUTE
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localised variant (classic annular rash)
|
with cosmetic concerns
1st line – 

topical or intralesional corticosteroids

Topical or intralesional corticosteroids can be offered. Clobetasol is a potent topical corticosteroid used with or without a hydrocolloid dressing. It is easy for the patient to apply and is painless.

Intralesional corticosteroids can be used if topical corticosteroids have not induced any improvement after 8 weeks, but this can be painful.

Long-term use of superpotent corticosteroid creams can cause skin atrophy. Injections can result in depressed scarring if not given by trained personnel.

Primary options

clobetasol topical: (0.05%) apply a small amount to the affected area(s) once daily (or once weekly if occlusive dressing is used) for up to 8 weeks, maximum 50 g/week

Secondary options

triamcinolone acetonide: (5 mg/mL) 0.1 mL intralesionally every 6-8 weeks; two to three treatments are usually sufficient

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generalised variant (widespread macular rash)

1st line – phototherapy

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ACUTE
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generalised variant (widespread macular rash)
1st line – 

phototherapy

Small studies demonstrate that using oral psoralen reduces the risk of burning during treatment. Lesions tend to clear within 4 months but the relapse rate is high.[40]

If relapse occurs, extending PUVA phototherapy treatment by up to an extra month is possible, termed remission PUVA, but the risk of skin cancer is higher.

Narrow-band UV-B may be effective in some patients.[41]

1st line – hydroxychloroquine or chloroquine

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ACUTE
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generalised variant (widespread macular rash)
1st line – 

hydroxychloroquine or chloroquine

While there is limited good quality evidence for their use in this indication, hydroxychloroquine and chloroquine are the most widely supported and most often used first-line agents.[42][32] Hydroxychloroquine is the preferred option as there is less risk of ocular toxicity compared to chloroquine. Results from one retrospective analysis suggest that chloroquine might be beneficial for patients who have previously failed treatment with hydroxychloroquine.[42]

Ocular monitoring is required with these drugs.

Primary options

hydroxychloroquine: 3-6 mg/kg/day orally given once daily or in 2 divided doses, maximum 400 mg/day

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Secondary options

chloroquine phosphate: consult specialist for guidance on dose

2nd line – isotretinoin or dapsone

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ACUTE
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generalised variant (widespread macular rash)
2nd line – 

isotretinoin or dapsone

The use of isotretinoin as a second-line treatment is based on historical case reports demonstrating significant improvement.[43] However, there are no recent data to support its use. Isotretinoin is associated with potentially serious adverse effects and requires careful monitoring.[44] In the US, isotretinoin can be prescribed only through the iPLEDGE system. iPLEDGE: registration scheme for isotretinoin Opens in new window Providers, pharmacies, and patients must register with the system in order to prescribe the drug. It is contraindicated in pregnancy. Women of childbearing age should use additional contraception. Improvement can take up to 3 months.[45]

A number of case reports have demonstrated the efficacy of dapsone in the management of generalised granuloma annulare. However, it has more risks and adverse effects associated with its use compared to isotretinoin, but also appears to be more efficacious.[36] It shows an initial good response, but high relapse rate on cessation of therapy.[46] Reticulocyte count and methemoglobin levels should be monitored weekly during therapy with dapsone, owing to risk of haemolytic anaemia.

Primary options

isotretinoin: 0.5 to 1 mg/kg/day orally for 6 months

OR

dapsone: 100 mg orally once daily for up to 8 weeks

3rd line – systemic anti-inflammatory agents

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ACUTE
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generalised variant (widespread macular rash)
3rd line – 

systemic anti-inflammatory agents

Systemic anti-inflammatory agents may be trialled if treatment with hydroxychloquine, chloroquine, isotretinoin, dapsone, or phototherapy has been unsuccessful.

Many drugs have been tried, including corticosteroids, methotrexate, pentoxifylline, ciclosporin, and chlorambucil. A specialist should be consulted on specific drug regimens, as combinations of these drugs may be used.

Evidence for ciclosporin suggests that patients respond within weeks and stay symptom-free for up to 1 year.[47] In studies involving children, symptoms resolved within 4 weeks and patients remained asymptomatic for up to 2.5 years after stopping treatment.[50]

Case reports and small case series suggest a potential role for tumour necrosis factor (TNF)-alpha inhibitors, such as adalimumab, in the management of widespread, recalcitrant GA.[48]

Primary options

prednisolone: consult specialist for guidance on dose

OR

methotrexate: consult specialist for guidance on dose

OR

pentoxifylline: consult specialist for guidance on dose

OR

ciclosporin: consult specialist for guidance on dose

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OR

chlorambucil: consult specialist for guidance on dose

OR

adalimumab: consult specialist for guidance on dose

perforating variant (crusted or ulcerated lesion)

1st line – isotretinoin

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ACUTE
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perforating variant (crusted or ulcerated lesion)
1st line – 

isotretinoin

In the UK, isotretinoin is prescribed under the Pregnancy Prevention Programme (PPP), while in the US, it can be prescribed only through the iPledge system. iPLEDGE: registration scheme for isotretinoin Opens in new window Contraindicated in pregnancy. Women of childbearing age should use additional contraception.

Improvement can take up to 3 months.[45]

Primary options

isotretinoin: 0.5 to 1 mg/kg/day orally for 6 months

subcutaneous variant (soft nodule)

1st line – conservative management

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ACUTE
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subcutaneous variant (soft nodule)
1st line – 

conservative management

Demonstrated cases of subcutaneous GA require only reassurance, as the lesions are benign, and surgery does not affect their likelihood to recur.

patch variant (erythematous plaques)

1st line – conservative management

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ACUTE
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patch variant (erythematous plaques)
1st line – 

conservative management

Rare; no specific treatment established. Usually left to resolve.

If persistent, treatment approaches can be based on therapy for generalised GA.

Phototherapy (with NB-UVB or PUVA) may be particularly effective for this variant.[49]

1st line – topical corticosteroids

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ACUTE
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patch variant (erythematous plaques)
1st line – 

topical corticosteroids

Rare; no specific treatment established. Topical corticosteroids may be tried. Clobetasol is a potent topical corticosteroid used with or without a hydrocolloid dressing. It is easy for the patient to apply and is painless.[38]

Primary options

clobetasol topical: (0.05%) apply a small amount to the affected area(s) once daily (or once weekly if occlusive dressing is used) for up to 8 weeks, maximum 50 g/week

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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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