Induration can be caused by various medical conditions that trigger an inflammatory process, including infections, cancer, scarring, and other systemic conditions.
Infections
Several types of infections can lead to induration of soft tissues. For instance, cysts usually infected by microorganisms, like Staphylococcus aureus, can cause hardening of the cystic walls leading to induration. If the inflammation forms an abscess, (i.e., a collection of pus that builds up within tissues) further induration of the skin can be identified. Induration of the skin can also be caused by smaller inflammatory processes, such as infected insect bites or as a response to foreign bodies (e.g., wood chip).
Notably, induration of the skin is also used as a diagnostic method for individuals who may have been in contact with Mycobacterium tuberculosis, the bacteria that causes tuberculosis (TB). More specifically, the purified protein derivative (PPD) test is performed by injecting a small amount of fluid containing tuberculin (i.e., purified protein from culture of TB) under the top layer of the skin, usually on the forearm. After 48 to 72 hours, a trained healthcare worker evaluates the reaction by measuring the size of the induration (if any) created around the site of injection. There are different cutoffs to indicate a positive reaction depending on the individual’s risk factors. For people with high risk of TB (e.g., immunosuppression, HIV-positive individuals, recent close contacts with TB cases) the cutoff is ≥5 mm. In people with no known risk factors for TB, PPD is considered positive when the induration is ≥10 mm.
A positive reaction represents prior exposure to the TB antigen, not necessarily active infection. As a result, individuals with a positive PPD test may have an active TB infection, a past TB exposure (i.e., latent TB infection), received the BCG vaccine, or may even be infected by a variety of non-tuberculosis Mycobacteria. Further testing, like an interferon-gamma release assay (IGRA) or a chest X-ray, may be needed to rule out active TB infection.
Cancer
Cancer can lead to skin induration through various mechanisms, such as tumor infiltration, inflammation, and lymphatic obstruction. Skin cancers, like squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) often present as firm, indurated plaques or nodules, while melanoma may form thick, irregular masses due to malignant cell infiltration. In other cancers, like inflammatory breast cancer, cancer cells obstruct the dermal lymphatics, causing lymphedema and thickened skin around hair follicles, giving the skin the appearance of an orange peel. Finally, lymphoma, a cancer that affects immune cells, can result in enlarged lymph nodes and cutaneous induration (e.g., mycosis fungoides) due to infiltration by malignant T-cells.
Scarring
Scarring is the body’s natural way of replacing lost or damaged skin. After an injury, the skin produces collagen fibers to repair the damage, resulting in a fibrous tissue that looks and feels different from the surrounding skin. In certain cases, excessive collagen deposition causes firm, raised scars that extend beyond the wound's boundaries. These scars, known as keloid scars, seem to have a genetic predisposition, and they tend to be more common in individuals of African and Asian descent.
Other Systemic Conditions
Scleroderma
Scleroderma, also known as systemic sclerosis, is a rare autoimmune disorder in which normal tissue is replaced with thick, dense connective tissue. Scleroderma can affect any organ, but it usually involves the skin, gastrointestinal tract, lungs, heart, and kidneys. Skin lesions start in the fingers and move up across the arm to the shoulders, neck, and face. At first, the affected skin is swollen and doughy. Later when fibrosis develops, the skin becomes tight, shiny, smooth, and indurated.
Diabetes Mellitus
Diabetes mellitus can also be associated with induration as it frequently causes recurrent ulcers, especially on the bottom of the feet due to poor circulation and decreased sensation of the lower extremities. The areas of skin that have open sores can remain chronically inflamed, causing induration of the surrounding skin.
Panniculitis
Panniculitis is an inflammation of the subcutaneous (i.e., under the skin) fatty tissue that can also cause induration. An inflammatory process triggered by inflammatory disorders (e.g., Crohn disease), trauma, exposure to cold, or connective tissue disorders (e.g., lipoatrophy) can cause thickening of the skin, formation of firm nodules, and plaques.
Lymphedema
Lymphedema is a chronic condition caused by the accumulation of lymphatic fluid in the tissues due to impaired lymphatic drainage. This leads to swelling, inflammation, and fibrosis, most commonly in the arms or legs. This chronic fluid accumulation triggers an inflammatory response, leading to thickening and fibrosis of the skin and underlying tissues. In long-standing lymphedema, fat and fibrotic tissue replace the normal lymphatic structures, causing a leathery, thickened appearance often seen in elephantiasis.
Other
Occasionally, certain vaccines, medications, or biologic agents can cause a localized skin induration due to injection reactions. These indurations are usually temporary and resolve spontaneously once the inflammation subsides. Other medical procedures, like radiotherapy, can also result in induration due to damage to fibroblasts, the cells responsible for producing collagen and maintaining connective tissue. Radiation-induced induration is more common after radiation for breast cancer or head and neck tumors. In such cases, radiation may result in tightened, fibrotic skin and muscle stiffness.
