An inflammatory skin nodule is a palpable mass, often painful, that develops in the dermis or subcutis. Its size usually exceeds one centimeter, distinguishing it from a simple papule. Several diseases, whether infectious, autoimmune, or metabolic, can trigger the appearance of these lesions. Understanding the underlying mechanism guides the diagnosis and conditions the management.
Panniculitis and erythema nodosum: when the subcutaneous fatty tissue becomes inflamed
Panniculitis refers to inflammation of the fatty layer located beneath the skin. Among its forms, erythema nodosum is the most common. It manifests as firm, painful red or purplish nodules, primarily located on the anterior surface of the shins, sometimes on the arms.
Erythema nodosum is not an autonomous disease: it reflects a reaction of the body to a triggering factor. Three main categories of causes are identified. Bacterial infections (notably streptococci), fungal, or viral infections are at the forefront. Certain medications can also provoke this reaction. Finally, chronic inflammatory bowel diseases, such as Crohn’s disease or ulcerative colitis, are among the recognized triggers.
The nodules are often accompanied by fever, joint pain, and marked fatigue. To better understand the causes of inflammatory nodules on the skin, it is essential to distinguish these general signs from purely cutaneous manifestations, as the etiological assessment guides the treatment.
The diagnosis is based on clinical examination, supplemented by blood tests, a chest X-ray, and sometimes a skin biopsy. The treatment primarily targets the cause: stopping the suspected medication, antibiotic therapy in case of infection, or managing the underlying bowel disease. Rest and non-steroidal anti-inflammatory drugs relieve symptoms in most cases.
Prurigo nodularis: nodules linked to a neuro-immune disorder
Prurigo nodularis is characterized by extremely pruritic nodular lesions, symmetrically distributed across the body. Their number can exceed one hundred, and their size can reach three centimeters. The itching is so intense that it severely disrupts sleep and quality of life.
The origin of this disease is not fully understood, but it involves a combined dysregulation of the immune and neurological systems. Type 2 inflammation is thought to play a central role in maintaining the vicious cycle of itch-scratch-nodule. Heat, sweat, and skin irritation exacerbate the symptoms.
Dupilumab: the first targeted therapy for prurigo nodularis
Conventional treatments (topical corticosteroids, antihistamines, antidepressants) often prove insufficient against this disease. Since 2022, dupilumab (Dupixent) has become the first targeted therapy approved by the FDA for prurigo nodularis. This same molecule is currently being evaluated for European approval.
Phase 3 trials (PRIME and PRIME2) showed significant improvement in itch and near-complete resolution of nodular lesions in some patients after 24 weeks of treatment. A prospective real-world registry (BioDay), followed over 52 weeks, confirms sustained efficacy on itch, sleep, and quality of life, even in patients more severe than those included in clinical trials. However, complete remission remains rare.
Suppurative hidradenitis and nodular acne: infections and inflammation of the hair follicle
Two conditions related to the hair follicle cause recurrent inflammatory nodules, but through different mechanisms.
Suppurative hidradenitis
Suppurative hidradenitis (Verneuil’s disease) affects areas rich in apocrine glands: armpits, groin folds, perineal region. It is characterized by deep, painful nodules that progress to abscesses and then scar fistulas. The disease evolves in flare-ups and can become very debilitating.
Its mechanism combines follicular occlusion, secondary bacterial superinfection, and a disproportionate inflammatory response. Tobacco and obesity are documented aggravating factors. Management combines prolonged antibiotic therapy, surgery for chronic lesions, and, in severe forms, anti-TNF biologic therapies.
Severe nodular acne
Nodular acne represents the most severe form of common acne. The nodules, primarily located on the face, back, and chest, result from deep inflammation of the pilosebaceous follicle. Unlike superficial comedones, these lesions frequently leave scars.
Recent European recommendations emphasize the early initiation of oral isotretinoin in nodular forms to limit the risk of scarring. Regular biological monitoring and contraception for women of childbearing age remain prerequisites for this treatment.
Cutaneous granulomas and autoimmune diseases: nodules without infection
Some inflammatory nodules form without any infection. Cutaneous granulomas are a typical example: they are clusters of immune cells (macrophages, epithelioid cells) that organize in response to a persistent stimulus that the body cannot eliminate.
Sarcoidosis is the most well-known systemic cause of cutaneous granulomas. It can produce firm, painless nodules that are reddish-brown in color, on the face, limbs, or scars. The diagnosis is based on biopsy, which reveals a characteristic non-caseating granuloma.
Other autoimmune diseases generate cutaneous nodules through different pathways:
- Psoriasis, in its severe or atypical forms, can produce thick nodular plaques, particularly at the elbows and knees.
- Autoimmune blistering dermatoses (pemphigus, pemphigoid) can evolve into secondary nodular lesions, especially during superinfections or chaotic healing.
- Chronic cutaneous lupus sometimes forms deep nodules (lupus panniculitis), located on the cheeks, arms, or thighs.
In all these cases, the diagnostic assessment includes skin biopsy, immunological assessment, and imaging according to the clinical context. Treatment is based on immunomodulation: corticosteroids, methotrexate, or targeted biologic therapies depending on the identified pathology.
In the face of a persistent inflammatory nodule, consulting a physician remains the first step. The diversity of diseases involved, from benign erythema nodosum to systemic sarcoidosis, makes self-diagnosis risky. A skin biopsy often clarifies the diagnosis when clinical examination and blood tests are insufficient.