Granuloma anulare classic type L92.0

Author: Prof. Dr. med. Peter Altmeyer

All authors of this article

Last updated on: 24.05.2021

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Synonym(s)

annular granuloma; pseudorheumatoid nodules

History
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Colcott-Fox, 1895; Radcliffe Crocker, 1903

Definition
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Asymptomatic, chronic, necrobiotic, granulomatous inflammation of the skin, with formation of skin-coloured or slightly reddened papules and plaques that form characteristic anular structures.

Etiopathogenesis
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Pathogenesis unclear. A late type reaction involving cell-mediated immune processes is suspected.

Development after insect bites or other local traumas, in the context of infections (association with viral infections (e.g. Epstein-Barr virus, HIV, herpes zoster virus and SARS-CoV-2), autoimmune diseases of the thyroid gland, frequently in diabetes mellitus.

There is good casuistic evidence for drug-induced granuloma anulare. The following drugs were listed (cited from Boyoung Lee S): adalimumab (n=5), allopuriol (n=3); gold (n=2), infliximab (n=2), topiramate(n=2), amlodipine, calcitonin, diclofenac, etanercept, interferon alpha, paroxetine, thalidomide, phostal stalergenes; vemurafib (n=1 each) .

Of historical and pathogenetic interest is the occurrence of granuloma anulare with vitamin D3 therapy(granuloma anulare vigantolicum) in tuberculosis.

In former times often associated with tuberculosis. Possibly genetic predisposition.

Manifestation
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Occurs mainly in children and adolescents, preference for the female sex.

Localization
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Preferably acra, extensor sides of the joints, back of the hand and foot, back of the fingers.

Clinical features
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In the classic and most common anular granuloma, there is a solitary or few, circular or ring-shaped, completely asymptomatic ornaments that can reach a diameter of 1.0 to 3.0 cm. The ring or circular ornaments are composed of smaller, aggregated, solid, red or skin-coloured, surface-smooth nodules and plaques, about 0.1-0.3 cm in size. In most cases, the composite nodule structure is still visible even after a longer period of existence. Growth is slow and can last for many months. If 2 paple circles meet together, the result is arching, in places obliterating ornaments.

Typically, the individual florescence of the granuloma anulare does not exceed a maximum size of 5.0 cm.

In rare cases, however, an extreme expansion up to 10.0 cm may occur(Granuloma anulare giganteum) without any explanation being provided in individual cases.

Histology
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Circumscribed nodular sites of inflammation in the upper and middle dermis (rarely located in subcutaneous fatty tissue) with central necrobiosis and throughput with nuclear fragments. Characteristic is an enclosing palisade granuloma of lymphocytes, macrophages (histiocytes), fibroblasts and, more rarely, multinuclear giant cells. Occasionally also admixtures of eosinophilic leukocytes and plasma cells. Rarely vasculitic changes can be detected with leukocytoclasia. In the granuloma anulare of the interstitial type, less nodular but rather diffuse interstitial infiltrates of CD68-positive histiocytes and lymphocytes around alcian blue-positive mucin deposits in the reticular dermis are observed.

Diagnosis
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In particular for extensive forms: clarification of diabetes mellitus (daily blood sugar profile, glucose load test), X-ray of the lungs, Multitest Mérieux, focus search.

Differential diagnosis
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Necrobiosis lipoidica (when localized on the lower extremity): telangiectasia, sunken speckly shiny centre, mainly localized on the extensor lower legs.

Sarcoidosis: mainly in cool skin areas such as the face; typical diascopically detectable intrinsic infiltrate.

Rheumatoid nodules: positive rheumatoid factor or ANA.

Syphilid: positive syphilis diagnosis.

Lichen myxoedematosus: mainly on thighs, trunk, extensor sides of arms and back of hands, with dense, whitish to yellowish papules also in linear arrangement. Histology is diagnostic.

Lichen planus anularis: on flexor sides of joints and mucous membrane with typical Wickham's pattern. Histology is diagnostic.

Dermatitis, interstitial, granulomatous with arthritis: very rare, clinical picture has not yet acquired a sharp clinical contour.

Therapy
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  • Children: Wait for spontaneous remission, if necessary mask with foil, hydrocolloid foil (e.g. Varihesive extra thin) or adhesive plaster bandage. If necessary, occlusive dressing with topical glucocorticoids (e.g. Ecural Fatty Ointment).
  • Adults: Triamcinolone acetonide crystal suspension intralesional (e.g. Volon A 10 mg, 1:3-1:5 diluted with local anaesthetics, e.g. Scandicain), multiple, or occlusive dressing with fluorinated glucocorticoid ointments (e.g. Ultralan ointment). In older, otherwise therapy-resistant foci, cryosurgery with a closed system may be necessary: temperature at the stamp -180/-190 °C, only brief freezing. If necessary, repeat after 10-14 days.
The listed forms of therapy are empirical methods and require clinical evaluation (especially in view of the high spontaneous healing rate). See also the special forms of the anular granuloma.

Radiation therapy
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Especially in the case of generalized anular granuloma, a local PUVA cream therapy is an effective option.

Internal therapy
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Antimalarial drugs e.g. Hydroxychloroquine Initial 400 mg/day for 4-8 weeks, then 200 mg/day and further reduction depending on the findings.

Alternative: In case of generalised infestation ( Granuloma anulare disseminatum), test with fumaric acid esters e.g. Fumaderm Tbl (well effective; off-label use).

Alternative: Retinoids ( Acitretin) in an initial dosage of 0.5 mg/kgkgkg and a maintenance dose of 0.1-0.2mg/kg/kg.

Alternatively, retinoids in combination with glucocorticoids. Acitretin dose as before; glucocorticoid dose (prednisolone) initial 0.5mg/kg/kgkg, maintenance dose (several months) with 0.05-0.1 mg/kg/kg.

Alternatively, dapsone (DADPS). Initial 100-200 mg/day p.o. with slow dose reduction.

Progression/forecast
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Months or even years of continuous but also recurrent course. Often (especially in children) spontaneous healing is to be expected (consider the consequences of therapy!).

Literature
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  1. Boyoung Lee S et al (2016) Vemurafenib-induced granuloma anulare. JDDG 14: 305-308
  2. Breuer C (2005) Therapy of noninfectious granulomatous skin diseases with fumaric acid esters. Br J Dermatol 152: 1290-1295
  3. Fölster-Holst R et al (1996) Unusual circulatory variant of a generalized granuloma anulare. Dermatologist 47: 53-57
  4. Guardiano RA et al (2003) Generalized granuloma annulare in a patient with adult onset diabetes mellitus. J Drugs Dermatol 2: 666-668
  5. Kolde G (2014) Granulomatous dermatoses. Act Dermatol 40: 193-204
  6. Limas C (2004) The spectrum of primary cutaneous elastolytic granulomas and their distinction from granuloma annulare: a clinicopathological analysis. Histopathology 44: 277-282
  7. Looney M et al (2004) Isotretinoin in the treatment of granuloma annulare. Ann Pharmacother 38: 494-497
  8. Proske U et al (2011) Granuloma anulare giganteum et disseminatum. Act Dermatol 37: 210-212
  9. Radcliffe Crocker H (1903) Diseases of the Skin. 3rd edn., HK Lewis, London

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