While the exact etiology of NPDs remains unknown, they are thought to be polymicrobial infections, where a synergistic interaction of bacteria, viruses, and fungi contributes to their pathogenesis. Porphyromonas gingivalis, Prevotella intermediaand Fusobacterium nucleatum are often involved in the production of toxins capable of causing significant damage to the periodontium.4 However, the role of these microorganisms is complex. It is unclear whether they are the primary causative agents or simply opportunistic pathogens that thrive in an exposed environment, but evidence suggests that host factors play an important role. People with weakened immune systems, malnutrition, tobacco use or stress are more susceptible to NPD, indicating that pre-existing conditions create a favorable environment for these infections to flourish.
The non-infectious nature of NPDs reinforces the importance of host factors, where these infections likely result from changes in the oral microbiome caused by underlying predispositions, leading to a dysbiotic state that favors pathogenic microbes.5,6
Specifically, other bacterial infections (e.g. gonorrhea, tuberculosis,7 and syphilis), viral infections (eg, herpes simplex virus and varicella zoster), and fungal infections (eg, candidiasis and histoplasmosis) are included in this category. These infections can present with a variety of clinical manifestations ranging from ulcers and erythema to tissue necrosis, often requiring specialized diagnostic techniques such as cultures or biopsies for confirmation. This recognition facilitates targeted treatment strategies and emphasizes the need for multidisciplinary collaboration in the management of these complex cases.
Inflammatory and immune conditions
Conditions associated with immune system dysregulation can lead to gingival inflammation without the typical accumulation of bacterial biofilm. Hypersensitivity reactions, such as contact allergy to dental materials or oral hygiene products, may manifest as localized or generalized gingivitis.8,9 Autoimmune disorders such as pemphigus vulgaris, membranous pemphigoid, and systemic lupus erythematosus can also affect the gums, causing inflammation, blistering, and ulceration. Granulomatous conditions such as sarcoidosis or Crohn’s disease may also present with gum involvement.
The diagnosis of these conditions requires a multidisciplinary approach, including a detailed medical history, clinical examination, and possibly laboratory tests and biopsies. Treatment strategies vary depending on the underlying cause and may include topical or systemic medications, allergen avoidance, and working with medical specialists.10,11
Reactive processes
Triggers can range from faulty restorations and ill-fitting dentures to broken teeth and orthodontic appliances. The resulting lesions usually emerge from the gingival sulcus, displacing the gingival margin. Common examples include fibrous hyperplasia (fibrous epulis), pyogenic granuloma, and peripheral giant cell granuloma. These lesions can vary in appearance from firm pink overgrowths to vascular, ulcerated masses. Accurate diagnosis often requires identification and treatment of the underlying irritant, as failure may result in recurrence of the lesion.12,13
Neoplastic disorders
Premalignant conditions such as leukoplakia and erythroplakia may precede the development of oral squamous cell carcinoma (OSCC), the most common malignant neoplasm affecting the gums. Although not all lesions develop into cancer, their early detection is vital. The NPIGD classification emphasizes the importance of careful oral examinations, identification of suspicious lesions, and early biopsy to detect dysplasia or early malignancy, allowing early intervention and improved patient prognosis.14
Malignant neoplasms, including squamous cell carcinoma or lymphoma, pose a more significant threat due to their aggressiveness and require early diagnosis and intervention.15 While the exact etiology of these neoplasms remains unclear, possible contributing factors include genetic predispositions, chronic irritation, viral infections, and immune system dysfunction. A thorough clinical examination, supplemented by biopsy and histopathological analysis, is essential for accurate diagnosis and appropriate management.16,17
Endocrine, nutritional and metabolic diseases
These systemic conditions can manifest in the oral tissues, leading to gingival inflammation and enlargement independent of plaque buildup. Vitamin C deficiencies (scurvy) can cause bleeding gums and ulceration. In addition, hormonal imbalances, as seen in diabetes mellitus, can predispose individuals to excessive gum inflammation, and metabolic bone diseases such as Paget’s disease can also contribute to non-plaque-induced gum changes.18
Traumatic damage (physical, mechanical, chemical and thermal insults)
Traumatic lesions result from physical or chemical damage to the gingival tissues, regardless of plaque build-up. Examples include friction keratosis caused by chronic irritation, chemical burns from misuse of oral hygiene products, and physical trauma from accidental biting or aggressive tooth brushing. Recognition of traumatic injuries is crucial for proper diagnosis and treatment, which includes addressing the source of the trauma and promoting healing.
Pigmentation of the gums
This includes intrinsic pigmentation (eg nevi pigmentation, smoker’s pigmentation) and extrinsic pigmentation (eg amalgam tattoos). While these pigmentations do not directly cause gingivitis, they can be critical clinical findings for the diagnosis and management of NPIGD.19
