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Cutaneous Granulomatosis: a Comprehensive Review

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Abstract

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.

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Abbreviations

DCs:

Dendritic cells

T cells:

T lymphocytes

MΦs:

Macrophages

TLR:

Toll-like receptors

NOD:

Nucleotid-binding oligomerization domain

DAMPs:

Damage-associated molecular patterns

PAMPs:

Pathogen-associated molecular pattern

IFN:

Interferon

M1:

Macrophages 1

M2:

Macrophages 2

IL:

Interleukin

APCs:

Antigen presenting cells

Th:

T helper cells

GA:

Granuloma annulare

HLA:

Human leukocyte antigen

TNF:

Tumor necrosis factor

NL:

Necrobiosis lipoidica

P.:

Propionibacterium

IGD:

Interstitial granulomatous dermatitis

PNGD:

Palisaded neutrophilic and granulomatous dermatitis

RGD:

Reactive granulomatous dermatitis

Mtb:

Mycobacterium tuberculosis

DG-SIGN:

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

PDT:

Photodynamic therapy

MAL-PDT:

Methyl aminolevulinate-photodynamic therapy

PUVA:

Psoralen and UVA

M.:

Mycobacterium

PCR:

Polymerase chain reaction

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Acknowledgements

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.

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  1. Benedetta Terziroli Beretta-Piccoli and Carlo Mainetti contributed equally to this work.

Authors and Affiliations

  1. Epatocentro Ticino, Lugano, Switzerland

    Benedetta Terziroli Beretta-Piccoli

  2. Department of Dermatology, Bellinzona Regional Hospital, Bellinzona, Switzerland

    Carlo Mainetti

  3. Cité générations, Onex, Switzerland

    Marie-Astrid Peeters

  4. Clinique de Dermatologie, Hôpitaux Universitaires de Genève, Rue Gabrielle Perret-Gentil 4, CH-1211, Genève, Switzerland

    Emmanuel Laffitte

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  1. Benedetta Terziroli Beretta-Piccoli
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Terziroli Beretta-Piccoli, B., Mainetti, C., Peeters, MA. et al. Cutaneous Granulomatosis: a Comprehensive Review. Clinic Rev Allerg Immunol 54, 131–146 (2018). https://doi.org/10.1007/s12016-017-8666-8

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