Everything you need to know about inflammatory nodules.

Inflammatory nodules are fairly severe skin lesions, taking the form of bumps or protrusions. Due to their significant size, which can reach several centimetres, they are often painful and sensitive to touch. The presence of subcutaneous nodules is a sign of an active inflammatory process in the skin. These spots can develop in several contexts, in cases of nodular acne for example, or autoimmune diseases.

In fact, some inflammatory nodules occur as a result of nodular prurigo, a disease linked to a disturbance in the immune and neurological systems, or Verneuil's disease. The latter is thought to be caused by occlusion of the pilosebaceous follicle, coupled with inflammation and infection of the dermis and hypodermis. However, these conditions are relatively rare. Nodules are most commonly found in people suffering from nodular acne.

The formation of a nodule involves several biological events and begins with the infiltration of inflammatory cells into the dermis, usually triggered by pathogens such as bacteria. The immune system is then activated, leading to the migration of macrophages to the affected area. Through their Toll-like receptors, these cells identify and phagocytose the pathogens. However, in parallel, the macrophages release pro-inflammatory cytokines that attract other immune cells, such as neutrophils. This cellular recruitment causes local swelling under the skin, forming a mass that is the precursor of the nodule.

As cells gather, the inflammatory response is amplified by the release of mediators that increase vascular permeability. This leads to an influx of plasma and proteins into the tissues, which intensifies swelling. Furthermore, persistent inflammation stimulates the production of the growth factor TGF-β, promoting the proliferation of fibroblasts. This results in a heightened production of collagen fibres and other components of the extracellular matrix, giving the nodule its hard and firm texture.

It is crucial to promptly address inflammatory nodules due to the aesthetic damage they cause and the impact they can potentially have on a patient's quality of life. This is particularly true in the case of nodular acne, where numerous nodules may be present, especially on the face. Furthermore, nodules pose a scarring risk high. Managing them as early as possible helps to minimise the risk of permanent marks. The treatments for inflammatory nodules vary, particularly depending on their cause, location, and the severity of symptoms:

• Topical treatments can be prescribed in the case of inflammatory nodules.

  Inflammatory nodules can initially be treated with topical creams or gels. Corticosteroids, for example, are anti-inflammatory agents that reduce the production of pro-inflammatory cytokines and inhibit the migration of immune cells. They also stabilise the membranes of lysosomes, limiting the release of enzymes that break down tissues, which reduces inflammation and swelling of the nodule.

  Topical antibiotics, such as clindamycin or erythromycin, often used for acne, also target nodules. By inhibiting the synthesis of bacterial proteins, they block the multiplication of bacteria, thus reducing the bacterial load and pro-inflammatory mediators. Finally, topical retinoids, such as tretinoin or adapalene, act on the differentiation of epidermal cells and modulate the expression of genes related to cell growth. They also decrease sebum production, creating a less favourable environment for bacterial proliferation.

• It is possible to use oral medications to eliminate nodules.

  Inflammatory nodules can also be treated with oral antibiotics, such as doxycycline and minocycline, which inhibit the synthesis of bacterial proteins and modulate the immune response. These drugs also target matrix metalloproteinases, thereby reducing the degradation of the extracellular matrix and the infiltration of inflammatory cells. Isotretinoin can also be mentioned, a treatment of choice for severe acne cases, such as nodulocystic acne. This derivative of vitamin A reduces the size and activity of the sebaceous glands, limiting the production of sebum while preventing the obstruction of hair follicles and controlling inflammatory lesions.

• Certain localised techniques can be used in the case of inflammatory nodules.

  Particularly effective for nodules of viral origin, cryotherapy relies on the rapid freezing of the nodule tissues. This method typically uses liquid nitrogen to crystallise the intracellular fluids, which leads to the apoptosis of the nodule cells. Concurrently, a tissue repair process is initiated to restore the damaged tissues. When the nodules are purulent or present a risk of malignancy, a surgical excision can be performed. This technique allows for the complete removal of the nodule and its analysis to determine its nature.

• The nodules can be removed with a CO2 laser.

  Finally, it is possible to eliminate an inflammatory nodule using a CO2 laser. This emits at a wavelength of 10.6 µm, allowing it to target the water in tissues and vaporise it, which results in the destruction of damaged tissues. Generally well tolerated, the CO2 laser is particularly suitable for nodules with a fibrotic component or those not responding to traditional treatments.

Most inflammatory nodules are benign. However, they can sometimes conceal malignant tumours, such as basal cell carcinomas or squamous cell carcinomas. If there is any doubt about a nodule or subcutaneous lump, it is important to consult a dermatologist without delay. In such a scenario, it is preferable to establish an accurate diagnosis. If the nodule is indeed cancerous, radiotherapy or chemotherapy may be considered. Although it does not replace a medical diagnosis, the table below provides some understanding to determine if a nodule could be dangerous.

• HANCOX J. & al. Diagnosis and Treatment of Acne. American Family Physician (2004).

• SHALITA A. & al. Therapeutic considerations for severe nodular acne. American journal of clinical dermatology (2011).

• TANGHETTI E. & al. The Role of Inflammation in the Pathology of Acne. Journal of Clinical and Aesthetic Dermatology (2013).

• BHUSHAN R. & al. Guidelines of care for the management of acne vulgaris. Journal of the American Academy of Dermatology (2016).

• TIDY C. Skin and subcutaneous nodules. Patient (2021).