Nodules: How do they form?

Generally associated with inflammatory or infectious dermatoses, the subcutaneous nodules are a specific form of spots, most commonly appearing in the context of nodular acne. Compared to other spots, such as the papules or the pustules, nodules are distinguished by their firm consistency, their deep implantation in the skin, often at the level of the dermis, and their protruding appearance. They are sometimes painful, due to their significant size. The formation of a nodule involves several interconnected biological events and usually begins with a infiltration of inflammatory cells into the dermis.

This infiltration is typically triggered by pathogens such as bacteria or fungi, which elicit a response from the immune system and the migration of macrophages, white blood cells, through chemotaxis to the site of inflammation. Thanks to their Toll-like receptors, macrophages recognise pathogens and cellular debris before phagocytosing them, that is, digesting them. However, these immune cells also trigger the release of pro-inflammatory cytokines, such as interleukins-1 and 6, tumour necrosis factor TNF-α, and interferon gamma IFN-γ. These cytokines create an environment conducive to the infiltration of additional immune cells, such as T lymphocytes, neutrophils, and eosinophils. This massive recruitment of cells leads to a local swelling of the subcutaneous tissues which contributes to the formation of a palpable mass under the skin, a precursor to the nodule.

As cells gather, they release mediators that amplify the inflammatory response and increase vascular permeability, promoting the leakage of plasma and proteins into the interstitial tissue, which intensifies local swelling. Prostaglandins, also part of the cytokine family, are also recruited and play a role in the phenomena of vasodilation/vasoconstriction and in the sensitisation of nerve endings, which is the origin of the pain sometimes felt at the nodule sites. In parallel, chronic inflammation stimulates the production of the TGF-β growth factor, which increases the proliferation of fibroblasts and tissue development. The intensification of the synthesis of extracellular matrix fibres gives the nodule its firm consistency. When fibroblast proliferation is very pronounced, it is referred to as fibrosis.

Some subcutaneous nodules may conceal malignant tumours, such as basal cell carcinomas or squamous cell carcinomas. If in any doubt, do not hesitate to consult a dermatologist if you notice the presence of a lump under the skin.