What causes granuloma annulare?

What Causes Granuloma Annulare?

Pathophysiology

Granuloma annulare results from a cell-mediated hypersensitivity reaction to an unknown antigen, leading to a characteristic inflammatory response with collagen degeneration, mucin deposition, and palisaded or interstitial histiocyte infiltration. 1

The underlying mechanism involves:

• Delayed-type hypersensitivity reaction where inflammatory cells (primarily histiocytes and lymphocytes) trigger connective tissue degradation 1, 2
• Incomplete foreign-body granuloma formation that may represent a dysfunctional immune control mechanism, where the immune system continues sustaining granulomatous formation even after the initial antigen is no longer present 3
• Collagen degeneration with mucin deposition surrounded by palisaded histiocytes, creating the characteristic histologic pattern 1

Potential Triggers and Associations

While the exact etiology remains unknown, several triggers and disease associations have been documented:

Systemic Disease Associations

• Diabetes mellitus is associated with atypical presentations of granuloma annulare 1, 4
• Thyroid disorders have been linked to GA development 5, 1
• Lipid abnormalities are described in atypical cases 1
• Malignancy has been reported in association with GA 5, 1

Infectious Triggers

• HIV infection has been associated with GA 5
• Other infectious agents have been proposed but not definitively established 1, 4

Medication-Induced Cases

• TNF-α inhibitors paradoxically can both trigger and treat GA 2
• Interleukin-17A antagonists (secukinumab) have been reported to induce GA 2
• Various other medications have been implicated as potential triggers 4

Physical Triggers

• Trauma to the skin has been associated with lesion development 5
• Insect bites and other local injuries may precipitate lesions 4

Clinical Pitfalls

The majority of GA cases occur without any identifiable trigger or systemic association, making routine extensive workup unnecessary in typical localized presentations 1, 4. Reserve comprehensive evaluation for:

• Generalized or atypical presentations 1
• Patients with clinical features suggesting underlying systemic disease 4
• Refractory cases not responding to standard therapy 1

Avoid assuming all GA requires extensive investigation for diabetes or malignancy, as the evidence for these associations is primarily from case reports and small series rather than controlled studies 4.