Oral manifestations of systematic disease are those observations, changes, disease processes, metabolic problems and symptoms occurring elsewhere in the body but are detected in the oral cavity and oral secretions. Hyperglycemia can be detected by sampling saliva. Investigations into the influence of polycystic ovarian syndrome on the oral microbiome are continuing. Saliva sampling may be a non-invasive way to detect changes in the gut microbiome and changes in systemic disease. The association between the salivary microbiome and with Polycistic Ovarian Syndrome has been characterized. "[S]aliva microbiome profiles correlate with those in the stool, despite the fact that the bacterial communities in the two locations differ greatly. Therefore, saliva may be a useful alternative to stool as an indicator of bacterial dysbiosis in systemic disease." Another example is tertiary syphilis, where changes to dentition can occur. Syphilis infection can be associated with longitudinal furrows of the tongue.

Mineral and vitamin deficiencies can cause the tongue to appear beefy red and feel sore. Those deficiencies are iron, folate and vitamin B12. A Hairy Tongue may be an indication of Epstein Barr vius infection and is usually seen in those infected with HIV. Other systematic diseases that can cause the tongue to form Aphthous ulcers are: Crohn's Disease and Ulcerative Colitis, Behcet's Syndrome, pemphigus, herpes simplex, histoplasmosis, and reactive arthritis (Reiter's Syndrome).

The signs and symptoms of Kikuchi disease are fever, enlargement of the lymph nodes (lymphadenopathy), skin rashes, and headache. Rarely, enlargement of the liver and spleen and nervous system involvement resembling meningitis are seen. Often a bout of extreme fatigue can occur - often taking hold during latter parts of the day and the affected person can be more prone to fatigue from exercise.

In the early stages some patients may complain of a feeling of tightness around the teeth. Three signs/symptoms must be present to diagnose this condition:

- Severe gingival pain.

- Profuse gingival bleeding that requires little or no provocation.

- Interdental papillae are ulcerated with necrotic slough. The papillary necrosis of NUG has been described as "punched out".

Other signs and symptoms may be present, but not always.

- Oral malodor (intraoral halitosis).

- Bad taste (metallic taste).

Malaise, fever and/or cervical lymph node enlargement are rare (unlike the typical features of herpetic stomatitis). Pain is fairly well localized to the affected areas. Systemic reactions may be more pronounced in children. Cancrum oris (noma) is a very rare complication, usually in debilitated children. Similar features but with more intense pain may be seen in necrotizing periodontitis in HIV/AIDS.

HIV-SGD may be the presenting sign of HIV infection. There may also be xerophthalmia (dry eyes) and arthralgia (joint pain), similar to Sjögren syndrome.

Necrotizing gingivitis is part of a spectrum of disease termed necrotizing periodontal diseases. It is the most minor form of this spectrum, with more advanced stages being termed necrotizing periodontitis, necrotizing stomatitis and the most extreme, cancrum oris.

Acute necrotizing ulcerative gingivitis (ANUG) refers to the clinical onset of NUG. The word acute is used because usually the onset is sudden. Other forms of NUG may be chronic or recurrent.

Necrotizing ulcerative periodontitis (NUP) is where the infection leads to attachment loss, and involves only the gingiva, periodontal ligament and alveolar ligament. Progression of the disease into tissue beyond the mucogingival junction characterizises necrotizing stomatitis.

Persons with aphthous stomatitis have no detectable systemic symptoms or signs (i.e., outside the mouth). Generally, symptoms may include prodromal sensations such as burning, itching, or stinging, which may precede the appearance of any lesion by some hours; and pain, which is often out of proportion to the extent of the ulceration and is worsened by physical contact, especially with certain foods and drinks (e.g., if they are acidic). Pain is worst in the days immediately following the initial formation of the ulcer, and then recedes as healing progresses. If there are lesions on the tongue, speaking and chewing can be uncomfortable, and ulcers on the soft palate, back of the throat, or esophagus can cause painful swallowing. Signs are limited to the lesions themselves.

Ulceration episodes usually occur about 3–6 times per year. However, severe disease is characterized by virtually constant ulceration (new lesions developing before old ones have healed) and may cause debilitating chronic pain and interfere with comfortable eating. In severe cases, this prevents adequate nutrient intake leading to malnutrition and weight loss.

Aphthous ulcers typically begin as erythematous macules (reddened, flat area of mucosa) which develop into ulcers that are covered with a yellow-grey fibrinous membrane that can be scraped away. A reddish "halo" surrounds the ulcer. The size, number, location, healing time, and periodicity between episodes of ulcer formation are all dependent upon the subtype of aphthous stomatitis.

Erythema nodosum is a form of panniculitis characterised by tender red nodules, 1–10 cm, associated with systemic symptoms including fever, malaise, and joint pain. Nodules may become bluish-purple, yellowing, and green, and subside over a period of 2–6 weeks without ulcerating or scarring. Erythema nodosum is associated with infections, including Hepatitis C, EBV and tuberculosis, Crohn's disease and sarcoidosis, pregnancy, medications including sulfonamides, and some cancers, including Non-Hodgkin lymphoma and pancreatic cancer.

IgG4-related disease has been described as an indolent condition. Although possibly based on opinion rather than on objective assessments, symptoms, if any, are commonly described as mild in the medical literature. This can be in spite of considerable underlying organ destruction. People are often described as being generally well at the time of diagnosis, although some may give a history of weight loss.

Pain is generally not a feature of the inflammation. However it may occur as a secondary effect, for example due to either obstruction or compression.

Often diagnosis is made due to the presence of painless swellings or mass lesions, or due to complications of masses, e.g. jaundice due to involvement of the pancreas, biliary tree or liver. Symptoms are commonly attributed to other conditions and other diagnoses may have been made years before diagnosis, e.g. urinary symptoms in men attributed to common prostate conditions. Lesions may also be detected incidentally on radiological images, but can be easily misdiagnosed as malignancies.

Reported cases do include some significant symptoms or findings however:

Disease presentation varies widely from patient to patient, as UCTD is by definition nonspecific. Symptoms typically include constitutional complaints that are common to connective tissue diseases such as fatigue, a general sense of feeling unwell, and fever.

Other symptoms associated with UCTD include:

- dry eyes

- dry mouth

- hair loss

- joint inflammation

- joint pain

- oral ulcers

- positive ANA test

- raynaud's phenomenon

- sun sensitive rash

Lung involvement, such as nonspecific interstitial pneumonia, is a possible disease complication.

Human immunodeficiency virus salivary gland disease (abbreviated to HIV-SGD, and also termed HIV-associated salivary gland disease), is swelling of the salivary glands and/or xerostomia in individuals infected with human immunodeficiency virus.

Aphthous stomatitis is a common condition characterized by the repeated formation of benign and non-contagious mouth ulcers (aphthae) in otherwise healthy individuals. The informal term canker sores is also used, mainly in North America, although this may also refer to any mouth ulcer.

The cause is not completely understood, but involves a T cell-mediated immune response triggered by a variety of factors. Different individuals have different triggers, which may include nutritional deficiencies, local trauma, stress, hormonal influences, allergies, or genetic predisposition.

These ulcers occur periodically and heal completely between attacks. In the majority of cases, the individual ulcers last about 7–10 days, and ulceration episodes occur 3–6 times per year. Most appear on the non-keratinizing epithelial surfaces in the mouth (i.e. anywhere except the attached gingiva, the hard palate and the dorsum of the tongue), although the more severe forms, which are less common, may also involve keratinizing epithelial surfaces. Symptoms range from a minor nuisance to interfering with eating and drinking. The severe forms may be debilitating, even causing weight loss due to malnutrition.

The condition is very common, affecting about 20% of the general population to some degree. The onset is often during childhood or adolescence, and the condition usually lasts for several years before gradually disappearing. There is no cure, and treatments aim to manage pain, reduce healing time and reduce the frequency of episodes of ulceration. The term is from meaning "mouth ulcer".

The terms gingival hyperplasia and gingival hypertrophy have been used to describe this topic in the past. These are not precise descriptions of gingival enlargement because these terms are strictly histologic diagnoses, and such diagnoses require microscopic analysis of a tissue sample. Hyperplasia refers to an increased number of cells, and hypertrophy refers to an increase in the size of individual cells. As these identifications obviously cannot be performed with a clinical examination and evaluation of the tissue, the term "gingival enlargement" is more properly applied. Gingival enlargement has been classified according to cause into 5 general groups:

- Inflammatory enlargement

- Drug induced enlargement

- Enlargement associated with systemic diseases or conditions

- Neoplastic enlargement

- False enlargement.

Nearly all people with Behçet's disease present with some form of painful ulcerations inside the mouth. They are a form of aphthous ulcers or non-scarring oral lesions. The oral lesions are similar to those found in inflammatory bowel disease and can be relapsing. Painful genital ulcerations usually develop around the anus, vulva, or scrotum and cause scarring in 75 percent of the patients. Additionally, patients may present with erythema nodosum, cutaneous pustular vasculitis, and lesions similar to pyoderma gangrenosum.

Patients with acute GPP experience the eruption of multiple isolated sterile pustules generalized over the body, recurrent fevers, fatigue, and laboratory abnormalities (elevated ESR, elevated CRP, combined with leukocytosis).

IgG4-related disease (IgG4-RD), formerly known as IgG4-related systemic disease, is a chronic inflammatory condition characterized by tissue infiltration with lymphocytes and IgG4-secreting plasma cells, various degrees of fibrosis (scarring) and a usually prompt response to oral steroids. In approximately 51–70% of people with this disease, "serum" IgG4 concentrations are elevated during an acute phase.

It is a relapsing–remitting disease associated with a tendency to mass forming, tissue-destructive lesions in multiple sites, with a characteristic histopathological appearance in whichever site is involved. Inflammation and the deposition of connective tissue in affected anatomical sites can lead to organ dysfunction, or even organ failure, if not treated.

Early detection is important to avoid organ damage and potentially serious complications. Treatment is recommended in all symptomatic cases of IgG4-RD and also in asymptomatic IgG4-RD involving certain anatomical sites.

Lipodermatosclerosis is a form of panniculitis associated with chronic venous insufficiency that presents with brown indurations on the front of the shins. It may be associated with pain and other signs of chronic venous insufficiency. The exact cause is unknown.

Other forms include:

- Subcutaneous fat necrosis of the newborn, a form of panniculitis occurring in newborns that is usually self-resolving, that may be a result of hypoxic injury to relatively high levels of brown fat.

- Sclerema neonatorum, affecting premature births.

- Weber–Christian disease, a symmetrical form of the disease of unknown origin occurring in middle-aged women.

- Lupus erythematosus panniculitis, panniculitis associated with lupus erythematosus.

- Forms associated with use of high doses of systemic corticosteroids during rapid corticosteroid withdrawal, and from the injection of silicone or mineral oils.

Kikuchi disease or Kikuchi-Fujimoto disease was described in 1972 in Japan. It is also known as histiocytic necrotizing lymphadenitis, Kikuchi necrotizing lymphadenitis, phagocytic necrotizing lymphadenitis, subacute necrotizing lymphadenitis, and necrotizing lymphadenitis.

It was first described by Dr Masahiro Kikuchi (1935–2012) in 1972 and independently by Y. Fujimoto.

Gingival enlargement may be caused by a multitude of causes. The most common is chronic inflammatory gingival enlargement, when the gingivae are soft and discolored. This is caused by tissue edema and infective cellular infiltration caused by prolonged exposure to bacterial plaque, and is treated with conventional periodontal treatment, such as scaling and root planing.

Gingivitis and gingival enlargement are often seen in mouth breathers, as a result of irritation brought on by surface dehydration, but the manner in which it is caused has not been demonstrated.

The accumulation and retention of plaque is the chief cause of inflammatory gingival enlargement. Risk factors include poor oral hygiene, as well as physical irritation of the gingiva by improper restorative and orthodontic appliances.

Arthralgia is seen in up to half of people, and is usually a non-erosive poly or oligoarthritis primarily of the large joints of the lower extremities.

Acute, tender, erythematous plaques, nodes, pseudovesicles and, occasionally, blisters with an annular or arciform pattern occur on the head, neck, legs, and arms, particularly the back of the hands and fingers. The trunk is rarely involved. Fever (50%); arthralgia or arthritis (62%); eye involvement, most frequently conjunctivitis or iridocyclitis (38%); and oral aphthae (13%) are associated features.

von Zumbusch (acute) generalized pustular psoriasis, (acute GPP) is the most severe form of generalized pustular psoriasis, and can be associated with life-threatening complications.

SS can be classified based upon the clinical setting in which it occurs: classical or idiopathic SS, malignancy-associated SS, and drug-induced SS.

Relapsing polychondritis may affect many different organ systems of the body. At first, some people with the disease may have only nonspecific symptoms such as fever, weight loss, and malaise.

The disease usually affects the lower legs or scrotum. The swelling is accompanied by rough nodules or wart-like plaques on the skin. If the disease is not treated, it eventually results in pain and immobility.