Understanding Subcutaneous Nodules: Causes Overview

Certainly, let’s delve deeper into some of the key causes of subcutaneous nodules:

Inflammatory Conditions:

1. Rheumatoid Arthritis (RA):

   • RA nodules are typically found in 20-30% of RA patients.
   • They commonly develop over pressure points or areas prone to repeated trauma.
   • Histologically, RA nodules consist of central fibrinoid necrosis surrounded by palisading histiocytes, fibroblasts, and lymphocytes.

2. Granulomatosis with Polyangiitis (GPA):

   • Formerly known as Wegener’s granulomatosis, GPA can cause nodules due to necrotizing vasculitis affecting small and medium-sized vessels.
   • The nodules in GPA often involve the upper respiratory tract and lungs but can also appear in the skin.

3. Sarcoidosis:

   • Sarcoidosis nodules result from non-caseating granulomas and can affect multiple organs, including the skin, lungs, lymph nodes, and eyes.
   • Skin involvement occurs in around 25% of sarcoidosis cases, presenting as erythematous, violaceous, or hyperpigmented nodules.

4. Erythema Nodosum:

   • This is a type of panniculitis characterized by septal inflammation in subcutaneous fat.
   • Erythema nodosum can be associated with infections (e.g., streptococcal), inflammatory bowel disease, medications, or pregnancy.

Infections:

1. Abscesses:

   • Subcutaneous abscesses are localized collections of pus due to bacterial infections, commonly caused by Staphylococcus aureus or Streptococcus species.
   • Treatment involves incision and drainage, along with appropriate antibiotics.

2. Tuberculosis (TB):

   • Cutaneous TB can present as nodules, ulcers, or papules, with nodular TB being less common than other forms.
   • Nodular TB may result from direct inoculation, hematogenous spread, or lymphatic dissemination.

3. Fungal Infections:

   • Sporotrichosis is a fungal infection caused by Sporothrix schenckii, leading to subcutaneous nodules along lymphatic channels (sporotrichoid pattern).

Neoplastic Causes:

1. Lipomas:

   • Lipomas are the most common benign soft tissue tumors, composed of mature adipocytes.
   • They are typically slow-growing, painless, and mobile under the skin.

2. Dermatofibromas:

   • Dermatofibromas are fibrous nodules that often arise after minor trauma, such as insect bites or skin injuries.
   • They are characterized by a central fibroblast-rich core and surrounding collagenous tissue.

3. Neurofibromas:

   • Neurofibromas are associated with neurofibromatosis type 1 (NF1) and type 2 (NF2), genetic disorders affecting the nervous system.
   • They can be cutaneous or deep-seated, arising from peripheral nerves.

4. Metastatic Cancer:

   • Subcutaneous nodules can result from metastases of various cancers, including breast, lung, colon, and melanoma.
   • These nodules often indicate advanced disease and may be associated with systemic symptoms.

Connective Tissue Disorders:

1. Systemic Lupus Erythematosus (SLE):

   • SLE can cause subcutaneous nodules, especially in areas subjected to pressure or trauma (e.g., elbows, knees).
   • These nodules, termed lupus profundus or subcutaneous lupus nodules, are typically non-tender and may resolve with systemic treatment.

2. Dermatomyositis:

   • Calcinosis cutis, a hallmark of dermatomyositis, can lead to subcutaneous nodules containing calcium deposits.
   • These nodules are often located over bony prominences or areas of chronic pressure.

3. Systemic Sclerosis (Scleroderma):

   • Scleroderma can cause calcinosis cutis, where calcium deposits form nodules in the skin, subcutaneous tissue, or muscles.
   • Calcinosis in scleroderma is associated with a poorer prognosis and may require surgical intervention.

Traumatic Causes:

1. Foreign Body Reaction:

   • Nodules can form in response to retained foreign materials, such as sutures, splinters, or inert substances like silicone.
   • Foreign body granulomas can develop, characterized by histiocytes surrounding the foreign material.

2. Reactions to Injections:

   • Some injections, including vaccines or medications, can lead to localized reactions and nodules at the injection site.
   • These reactions are often inflammatory in nature and may resolve with conservative management.

Vascular Disorders:

1. Hemangiomas:

   • Hemangiomas are vascular tumors that can occur in infancy (infantile hemangiomas) or adulthood (cavernous hemangiomas).
   • Subcutaneous nodules may form in cases of deep or combined hemangiomas involving the skin and subcutaneous tissues.

2. Kaposi Sarcoma:

   • In the context of HIV/AIDS, Kaposi sarcoma can present with subcutaneous nodules due to vascular proliferation caused by human herpesvirus-8 (HHV-8) infection.
   • Classic Kaposi sarcoma often involves the lower extremities, while AIDS-related Kaposi sarcoma may affect multiple sites.

Genetic and Congenital Conditions:

1. Xanthomas:

   • Xanthomas are lipid-filled nodules that can occur in familial hypercholesterolemia and other lipid metabolism disorders.
   • They result from the accumulation of cholesterol-rich macrophages in the skin.

2. Neurofibromatosis:

   • Neurofibromatosis type 1 (NF1) is characterized by neurofibromas, café-au-lait spots, Lisch nodules (iris hamartomas), and other manifestations.
   • Subcutaneous neurofibromas can cause nodules along peripheral nerves, leading to neurologic symptoms.

Endocrine Disorders:

1. Thyroid Nodules:

   • Thyroid nodules can be benign (e.g., adenomas, colloid nodules) or malignant (e.g., papillary, follicular, medullary, anaplastic carcinoma).
   • Fine-needle aspiration (FNA) biopsy is often used to evaluate thyroid nodules for malignancy.

2. Calciphylaxis:

   • Calciphylaxis, also known as calcific uremic arteriolopathy, can cause painful subcutaneous nodules due to calcification of small blood vessels.
   • It is most commonly seen in patients with end-stage renal disease (ESRD) and is associated with high mortality.

Iatrogenic Causes:

1. Granulomatous Reaction to Fillers:

   • Soft tissue fillers, such as hyaluronic acid or collagen injections, can sometimes lead to granulomatous reactions and nodules.
   • These reactions may require steroid injections or surgical removal of the filler material.

2. Medication Reactions:

   • Certain medications, such as corticosteroids, can cause subcutaneous nodules as a side effect, particularly with long-term use.
   • Drug-induced lupus can also present with nodules in the skin and subcutaneous tissues.

Miscellaneous Causes:

1. Foreign Body Granulomas:

   • Chronic exposure to foreign materials, such as silica, can lead to granulomatous reactions and nodular formations.
   • Occupational exposures and inhalation of foreign particles are common routes of entry for such materials.

2. Mycobacterial Infections:

   • Besides tuberculosis, atypical mycobacterial infections (e.g., Mycobacterium marinum, Mycobacterium avium-intracellulare) can cause subcutaneous nodules, especially in immunocompromised individuals.
   • These infections may require prolonged antimicrobial therapy for resolution.

3. Radiation Dermatitis:

   • Radiation therapy for cancer treatment can lead to fibrotic changes in the skin and subcutaneous tissues, resulting in nodular formations.
   • Management includes topical treatments for skin irritation and monitoring for late radiation effects.

Each of these causes has distinct clinical features, diagnostic approaches, and management strategies. A thorough evaluation by healthcare professionals, including dermatologists, rheumatologists, infectious disease specialists, and oncologists, is essential for accurate diagnosis and appropriate treatment of subcutaneous nodules.