Clinical Reviews in Allergy & Immunology

, Volume 54, Issue 1, pp 131–146 | Cite as

Cutaneous Granulomatosis: a Comprehensive Review

  • Benedetta Terziroli Beretta-Piccoli
  • Carlo Mainetti
  • Marie-Astrid Peeters
  • Emmanuel Laffitte


Cutaneous granulomatosis is a heterogeneous group of diseases, characterized by a skin inflammatory reaction triggered by a wide variety of stimuli, including infections, foreign bodies, malignancy, metabolites, and chemicals. From a pathogenic point of view, they are divided into non-infectious and infectious granulomas. Pathophysiological mechanisms are still poorly understood. Non-infectious granulomatous skin diseases include granuloma annulare, necrobiosis lipoidica, rheumatic nodules, foreign body granulomas, cutaneous sarcoidosis, and interstitial granulomatous dermatitis. Necrobiosis lipoidica is more frequent in diabetic patients. Infectious granulomas of the skin are caused by mycobacteria, in particular Mycobacterium tuberculosis or atypical mycobacteria; parasites, such as Leishmania; or fungi. Pathogenic mechanisms of M. tuberculosis-related granuloma are discussed. From a clinical point of view, it is useful to divide cutaneous granulomatosis into localized and more disseminated forms, although this distinction can be sometimes artificial. Three types of localized granulomatous lesions can be distinguished: palisaded granulomas (granuloma annulare, necrobiosis lipoidica, and rheumatoid nodules), foreign body granulomas, and infectious granulomas, which are generally associated with localized infections. Disseminated cutaneous granulomas can be divided into infectious, in particular tuberculosis, and non-infectious forms, among which sarcoidosis and interstitial granulomatous dermatitis. From a histological point of view, the common denominator is the presence of a granulomatous inflammatory infiltrate in the dermis and/or hypodermis; this infiltrate is mainly composed of macrophages grouped into nodules having a nodular, palisaded or interstitial architecture. Finally, we propose which diagnostic procedure should be performed when facing a patient with a suspected cutaneous granulomatosis.


Granulomatous disease Granuloma annulare Necrobiosis lipoidica Foreign body granulomas Infectious granulomas Sarcoidosis Interstitial granulomatous dermatitis 



Dendritic cells

T cells

T lymphocytes




Toll-like receptors


Nucleotid-binding oligomerization domain


Damage-associated molecular patterns


Pathogen-associated molecular pattern




Macrophages 1


Macrophages 2




Antigen presenting cells


T helper cells


Granuloma annulare


Human leukocyte antigen


Tumor necrosis factor


Necrobiosis lipoidica




Interstitial granulomatous dermatitis


Palisaded neutrophilic and granulomatous dermatitis


Reactive granulomatous dermatitis


Mycobacterium tuberculosis


DC-specific intercellular adhesion molecule-3-grabbing non-integrin


Photodynamic therapy


Methyl aminolevulinate-photodynamic therapy


Psoralen and UVA




Polymerase chain reaction



We kindly acknowledge the assistance of Professor Diego Vergani (MD, PhD) for his critical review of the pathogenesis section, and Professor Gürkan Kaya (MD) for providing the histological pictures.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Informed Consent

When necessary, informed consent has been collected from patients.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Epatocentro TicinoLuganoSwitzerland
  2. 2.Department of DermatologyBellinzona Regional HospitalBellinzonaSwitzerland
  3. 3.Cité générationsOnexSwitzerland
  4. 4.Clinique de DermatologieHôpitaux Universitaires de GenèveGenèveSwitzerland

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