Aetiology

Aetiology is not proven, but trauma, insect bite reactions, tuberculin skin testing, sun exposure, psoralen-UV-A phototherapy, and viral infections such as hepatitis B or C, HIV and herpes zoster have all been suggested as inciting factors.[9] Familial cases have been reported, and there is a possible link between generalised GA and the haplotype HLA BW35.[10] A weak association between GA and diabetes has been reported but is not established as a causative factor.[11] There have been similar loose associations with thyroid disease, and hyperlipidaemia.[12][13][14] Widespread GA has also been reported in patients with Hodgkin's disease, chronic lymphocytic leukaemia, and other haematological malignancies; release of cytokines by tumour cells may play a role.[6][8][15][16] There are reports of drug-induced GA associated with a number of drugs, including biological agents and with chemotherapeutics, such as vemurafenib.[17][18] Granulomatous eruptions (including GA) have been reported with the use of immune checkpoint inhibitors (PD-1/PD-L1 agents). [19]

Pathophysiology

Early work, based on T-cell populations found within GA papules, suggested that the cause of the disease was a delayed-type hypersensitivity reaction to an unknown antigen.[20] Other theories are a type 1 T-cell inflammatory response causing matrix degradation[21] and a disorder of elastic-tissue injury.[22] Treatments such as cryotherapy work purely by causing localised tissue damage by controlled frostbite. Topical and intralesional corticosteroids may have both anti-inflammatory and immunosuppressive actions. Isotretinoin, a systemic agent, works by altering DNA transcription, and this in turn may have an effect on the cytokine profile produced by this group of hyper-reactive T-cells.

Classification

Clinical variants[2][3][4][5][6]

Localised

  • Usually seen on backs of hands, feet, and elbows.

  • Classic annular appearance.

  • Most common subtype; accounting for 75% of all cases.

  • Typically asymptomatic.

  • Patients are often women in their 30s.

Generalised

  • Some physicians further subdivide 'generalised' GA into generalised annular GA and disseminated papular GA.

  • Defined as >10 lesions but usually hundreds to thousands of small flesh-coloured/yellow-brown macules and papules.

  • Rarely shows an annular or widespread patch arrangement.

  • Typically appears over torso and limbs in a symmetrical distribution.

  • May be associated with underlying malignancy, and is usually found in an older population, although the evidence for malignancy association is contradictory.

Subcutaneous

  • Deep dermal or subcutaneous nodules; associated dermal lesions may be present.

  • Typically found in children <5 years of age, commonly on the feet and fingertips.

  • No evidence of any progression to systemic disease.

Perforating

  • Rare variant.

  • Superficial papules on hands and fingers with a central umbilicated crust or ulcer.

  • Makes up 5% of all cases.

  • Can be painful and very itchy, especially if on the palmar aspect of the hand.

Patch

  • Rare variant.

  • Generally in intertriginous areas such as the inguinal creases and axillary vault.

  • Lesions are slightly infiltrated erythematous plaques with a palpable border, on which scattered papules may arise.

  • May be more responsive to phototherapy than other variants.

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