Granuloma anulare (overview) L92.-

Calcott Fox, 1895

Asymptomatic, chronic, necrobiotic, granulomatous inflammation of the skin (including subcutis), with formation of skin-colored or slightly red papules and plaques that develop into characteristic anular outline formations of varying size. Clinically, different clinical pictures, with different clinical morphology and prognosis are presented, which are united only by the common histopathological substrate (necrobiotic collagen degeneration with radiating histiocytic inflammatory reaction: palisade granulomas).

Clinical variants of the anular granuloma:

• Granuloma anulare classical type
• Granuloma anulare subcutaneous type (pseudorheumatoid nodule)
• Granuloma anulare erythematous type
• Granuloma anulare disseminatum type (Granuloma anulare disseminatum)
• Granuloma anulare perforating type (Granuloma anulare perforans)
• Granulomatosis disciformis chronica et progressiva (Miescher`s Granuloma)
• Granuloma anulare multiforme
• Granuloma anulare bullous type: rarely described after use of TNF-alpha-receptor antagonist)
• Actinic granuloma (also known as anular elastolytic giant cell granuloma) - variant of the anular granuloma in (extensively) UV-exposed areas?
• Granuloma anulare giganteum (rare variant of Granuloma anulare)

Rare disease. Exact incidence figures are not available. In large dermatological centers, 0.1-0.5% of all patients have a diagnosis of granuloma anulare. Isolated case reports of familial occurrence are known.

Etiology and pathomechanism are unknown. Hypothetically were considered:

• delayed type IV immune response to focal connective tissue aging
• trauma-induced necrobiosis
• malignant neoplasias
• diabetes mellitus, dyslipoproteinemia, autoimmune thyroiditis
• Infection triggering through various Pathogens (especially viruses)
• Drugs

For further details see below Granuloma anulare classic type

Prevalent in children and adolescents and young adults. In 2/3 of all patients, the disease begins before the age of 30. f>m=2:1. Casuistic reports of a familial cluster (Weidenthaler-Barth B 2017).

In the classic and most common granuloma anulare, there is a solitary, or a few, circular or annular, completely asymptomatic ring structures that may reach 1.0 to 3.0 cm in diameter. These rings are composed of smaller, aggregated, firm, surface-smooth nodules and plaques. Their growth is slow and may persist for many months. When 2 ring structures meet, arcuate ornaments result.

Typically, the single efflorescence of classic granuloma anulare does not exceed a maximum size of 5.0 cm.

In rare cases, however, an extreme extension up to 10.0 cm may occur (granuloma anulare giganteum), without any explanation in individual cases.

Number of lesions: 85% of patients have less than 10 foci. Rarer is the exanthematous granuloma anulare disseminatum, which occurs in episodes and is also asymptomatic, with multiple smaller and often only suggestive anular plaques.

Perforating granuloma anulare (granuloma anulare perforans) shows central umbilication with crusting.

Granulomatosis disciformis chronica et progressiva (Miescher`s granuloma) seems to have a special clinical status.

Circumscribed nodular foci of inflammation in the upper and middle dermis (rarely located in subcutaneous adipose tissue) with central necrobiosis and throughput of nuclear fragments and mucin. Characteristic is an enclosing palisade granuloma of lymphocytes, macrophages (histiocytes), fibroblasts, and rarely multinucleated giant cells. Sporadic admixtures of eosinophilic leukocytes and plasma cells. In granuloma anulare of the interstitial type, less nodular but rather diffuse interstitial infiltrates of CD68-positive histiocytes and lymphocytes are observed around alcian blue-positive mucin deposits in the reticular dermis. In this case, necrobiosis is absent. In the rare form of perforating granuloma anulare, there is exudation of degenerated connective tissue.

See below the individual clinical pictures.

Wide variation in the duration of the condition. Spontaneous cure within the first two years can be expected in about 60% of patients. In children, the spontaneous remission rate is 80-90%. Known to have a high local recurrence rate (about 40%).

1. Butsch F et al (2015) Granuloma anulare. Dermatologist 66: 867-87
2. Boyoung Lee S et al (2016) Vemurafenib-induced granuloma anulare. JDDG 14: 305-308
3. Kowalski L et al (20169 Vesicular granuloma anulare under etanercept or abatacept therapy. Nude Dermatol 42:38-40
4. Weidenthaler-Barth B (2017) Clinical and histological spectrum of palisaded granulomatous dermatitides:Granuloma annulare, necrobiosis lipoidica, rheumatoid nodules, and necrobiotic xanthogranuloma. Dermatologist 68:536-541.

See below the individual clinical pictures