The window of the body: oral signs of systemic disease. (Part XII).

The mouth has often been called the barometer of a person's health. Serious illnesses, conditions or genetic disorders may first present with mouth conditions such as unusual bleeding or multiple lumps and bumps in the mouth, extra or missing teeth or their premature loss. These mouth changes are frequently helpful in determining the underlying disease or its cause.

Unusual Bleeding in the Mouth

There is a wide range of diseases or conditions of the human body which may first be detectable, or whose diagnosis can be confirmed, by signs of bleeding within the mouth. The diseases or conditions that can affect children and teenagers include infectious mononucleosis, measles, hemophilia, leukemia, and vitamin deficiencies, particularly vitamins C and K.

Infectious mononucleosis ("mono" or" kissing disease")

Children usually become infected with the Epstein-Barr virus (EBV) that causes mono through saliva contaminated with EBV on fingers, toys, or other objects. Teenagers usually get EBV through direct transfer of saliva, such as shared straws or kissing. In the United States, it is estimated that approximately half of the population is exposed to EBV by college age.

Children less than four years of age typically experience fever, swollen, tender neck glands; sore throat; liver and spleen enlargement; runny nose or cough. Older children have similar symptoms but less often have an enlarged liver and spleen, runny nose and cough. In the mouth, the tonsils may be enlarged and may have pus on the surface. One can sometimes observe tiny bleeding spots on the roof of the mouth during the first day or two of the infection. The gums may also get red, sore, bleed and have a foul smell. Diagnosis can be confirmed by special laboratory tests.

Measles

Measles is an infection caused by a virus (paramyxovirus) that presently occurs only in children who are not given the available measles vaccine or, in rare instances, when the vaccine fails. Most cases start in the spring and are spread through contact with someone who has the infection and sneezes or coughs near them. The typical skin rash appears after symptoms of fever, lack of energy, runny nose, red eye and a cough.

The most distinctive early mouth sign of measles is Koplik spots on the lips, cheeks and roof of the mouth. These are numerous, small blue-white flat growths that look like grains of salt. Other mouth findings include a white yeast infection that can be rubbed off and bleeding, foul-smelling gums. The tonsils may also look enlarged. Developing adult teeth can be affected so that when they appear in the mouth they show pits and small holes in the enamel. Diagnosis is usually straightforward, based on the patient's symptoms and knowledge that measles is "going around." For a single or unusual case special laboratory tests are available.

Hemophilia

Hemophilia is a group of bleeding problems associated with a genetic lack of one of the clotting elements of the blood. The most famous historical cases are male children of the European royal families, many of whom died from a direct result or complications of uncontrolled bleeding. Presently, blood transfusions and replacing the missing clotting element spare many lives. Since hemophilia A (lack of blood factor VIII) is the most significant and common type it will be the only one discussed here.

Hemophilia A is known as a genetic X-linked disorder; females may have the defective gene, but the disease is almost always seen only in males. Failure of normal clotting after circumcision is typically one of the first signs that a bleeding disorder is present. The outward signs and symptoms vary from mild bleeding problems to severe, life-threatening bleeding. In toddlers, oral cuts or bruises from falls and bumps may result in significant blood loss. Even normal physical activity may result in internal bleeding of the skin (deep bruising), muscles and large joints such as the knee or elbow. Scar formation often results, causing crippling deformities of the joints. Sometimes, a tumor-like growth forms in the body or within the mouth. Routine dental treatment such as cleaning teeth may result in uncontrollable or delayed bleeding. Blood clotting screening (nonspecific) tests should be ordered for any child suspected of having this or other bleeding disorders.

Leukemia

Leukemia may affect both children and adults. For unknown reasons thought to be genetic and environmental, a stem cell in the bone marrow becomes cancerous as it develops, multiplying rapidly and preventing the marrow from making enough red blood cells, white blood cells or platelets. Leukemia can be classified into acute or chronic types with several subdivisions. Acute leukemias, if untreated, run an aggressive course and often result in the death of the patient within several months. Chronic leukemias usually run a milder course although, without treatment, the patient will also die. Certain genetic disorders or syndromes present an increased risk of developing leukemia. In addition to Down syndrome, these include such rare syndromes as adult Bloom syndrome, Schwachman syndrome, ataxia-lymphoma syndrome, Klinefelter syndrome, Fanconi's anemia and Wiskott-Aldrich syndrome.

Many of the signs and symptoms of leukemia are related to the significant reduction of white and red blood cells. Because there are fewer red blood cells that carry oxygen throughout the body, patients complain of no energy, easy tiring and shortness of breath upon mild physical activity. The cancerous cells can invade organs, such as the liver and spleen, and cause the lymph nodes to enlarge. Patients with leukemia may demonstrate easy bruising and bleeding resulting from the lack of blood platelets. Tiny bleeding points on the roof of the mouth may be seen, along with bleeding from the gums for no apparent reason. Deep mouth ulcers often appear, usually affecting the gums most severely. A widespread oral yeast infection is common, as are cold sores (fever blisters). Occasionally leukemic cells invade gum tissue, resulting in a widespread, boggy, nontender gum enlargement. Finally, the bone around the bottom of the tooth's root can become infected, causing a toothache.

Vitamin C and K deficiencies

In the US, significant vitamin deficiencies are uncommon. Children with malabsorption (food nutrients do not get into the blood) or eating disorders, teenagers who follow fad diets and people who have alcoholism are the groups most commonly affected. Vitamin C (ascorbic acid) is necessary for the proper formation of collagen, the major protein of cartilage, bone and connective tissue. This vitamin is present in a wide variety of fruits and vegetables and is especially abundant in citrus fruits such as oranges and grapefruit. Vitamin K is necessary for the proper formation of various proteins, including those involved in clotting. Vitamin K is present in a wide variety of green vegetables and is produced by intestinal bacteria.

In the US, a deficiency of vitamin C--scurvy--is usually limited to those people who lack an adequate diet of fresh fruits and vegetables. One of the commonly-affected groups is inner-city infants whose diet consists entirely of milk. The outward signs are related to a lack of collagen formation. For example, weakened blood vessel walls may result in the formation of bruises in the mouth. Wound healing is delayed and recently-healed wounds may break down. Children are particularly susceptible to painful bleeding just above the bone surface. Within the mouth, generalized gum swelling with spontaneous bleeding is observed, as are ulcers, loose teeth and loss of bone around the teeth. Untreated scurvy can lead to death from bleeding within the brain.

A lack of vitamin K may be seen in patients with malabsorption problems or in those whose intestinal bacteria have been eliminated by long-term use of broad-spectrum antibiotics. Oral blood thinners such as coumadin also reduce the normal activity of vitamin K. Insufficient vitamin K causes a lack of blood-clotting elements that result in gingival (gum) bleeding for no apparent reason. If uncorrected, death may result from uncontrolled bleeding.

Multiple Lumps or Bumps in the Mouth

Some common and uncommon diseases and conditions of the body are revealed by a display of generalized or individual multiple lumps or bumps (lesions) in the mouth. The tongue is a favorite site for these lesions; they may be exhibited at birth or in childhood in at least seven genetic diseases. Other conditions causing childhood lumps and bumps in the mouth include Crohn's disease and tuberous sclerosis.

Enlarged Tongue

An enlarged tongue most commonly occurs in children and can range from mild to severe. In infants, it may be manifested first by noisy breathing, drooling and difficulty in eating. In young children a lisp may develop, along with an open bite and a jutting lower jaw. If the tongue constantly sticks out from the mouth, it may develop sores, become infected and may even start to break down. Diseases that cause enlargement of the tongue from multiple lesions include Down syndrome and rare conditions such as hypothyroidism, Beckwith-Wiedemann syndrome, the mucopolysaccharidoses (MPS), multiple endocrine neoplasia syndrome type 2B (MEN 2B) and neurofibromatosis (von Recklinghausen's disease of the skin). In patients with hypothyroidism or Beckwith-Wiedemann syndrome, the tongue usually has a smooth generalized enlargement. The other listed conditions typically have multiple, separate bumps and lumps.

Hypothyroidism is caused by decreased levels of thyroid hormone in infancy; typically the patient exhibits lack of energy and fatigue; cool, dry, rough skin; swelling of the face, arms, and legs; huskiness of the voice; constipation and weakness. Not all of these signs might be readily apparent in the infant and a failure to grow normally might be the first indication of the disease. The general enlargement of the tongue results from an accumulation of certain substances in the deeper layers of the tongue; the lips may also appear thickened. The baby teeth and, later, the adult teeth may fail to erupt, although those that do appear normal. Abnormal thyroid hormone levels will confirm the suspected condition.

Beckwith-Wiedemann syndrome is a rare genetic disease that includes protrusion of part of the gut through the navel, enlarged organs such as the spleen and liver, increased height and the onset of diabetes within the first 30 days after birth. Affected children are more likely to get certain body organ tumors. The face may have a large reddish birthmark that covers the forehead and eyelids; the upper jaw tends to be underdeveloped. The main finding in the mouth is the overall tongue enlargement.

Down syndrome, caused by an extra gene located on chromosome 21, may result in mental retardation and many physical signs, including a flat face with a short nose, protruding lower lip, small rounded ears, loose joints, wide hands and feet, stubby fingers, extra neck skin and a lack of muscle tone in newborns. In the mouth, a common finding is a thick, enlarged tongue with numerous surface fissures (deep grooves). Teeth may be smaller than normal and either too many or too few. Genetic tests will confirm the diagnosis.

The mucopolysaccharidoses are very rare genetic diseases in which one of several enzymes, and thus an important group of tissue building blocks, is missing. Most types of MPS display some degree of mental retardation. Often, the affected person has pronounced features. Other symptoms may include stiff joints and cloudy corneas. There may be varying degrees of tongue enlargement. Other mouth findings include enlarged gums (especially in the front) and abnormally shaped crowns with pointed tips on the back teeth. In other forms of the disease, teeth do not erupt through the gums. Diagnosis is confirmed by laboratory tests.

Multiple neoplasia syndrome, type 2B (MEN 2B) is one of a group of rare genetic conditions characterized by tumors of the pancreas, adrenal glands, parathyroid/thyroid glands and the pituitary gland. In MEN 2B, the child or young adult will often develop thyroid cancer, adrenal tumors, and multiple bumps or lumps within the mouth. Patients usually have thin, long arms/legs with muscle loss. The face is narrow but the lips are thick and jut out. The upper eyelid is sometimes inside out and small bumps may be present on the eyelid. The first sign of the condition is multiple bumps in the mouth, most commonly on the tongue. The mouth bumps and those of the lips and eyes are actually benign nerve tumors that may appear on the inside of the cheeks, the gums, roof of the mouth and, commonly, at both corners of the mouth. Laboratory and genetic test values are necessary for a final diagnosis.

Neurofibromatosis is a relatively common genetic condition. Although there are at least eight different forms of the disease, the most common type is von Recklinghausen's disease of the skin. Patients exhibit multiple skin bumps that are usually harmless nerve tumors. The bumps may be present at birth but become much more numerous after puberty. They may get extremely large; the exact number of bumps varies greatly among patients. Another characteristic feature is the presence of colored spots on the skin that have been described as having a "coffee-mixed-with-milk" color. They are usually present at birth or appear during the first year of life. Freckles in the armpits are another common sign. The irises may have brown spots. Some patients may also develop brain tumors, mental retardation, seizures and curvature of the spine. In the mouth, it is common to find multiple bumps (nerve tumors) on the tongue with an increased roughness of the tongue surface. X-ray films of the jaws may show characteristic changes. Diagnosis is made from the presence of two or more of seven characteristic physical findings.

Granulomatous diseases

These conditions have a common feature, a characteristic type of inflammation with a special appearance under the microscope. Within this group of lesions, Crohn's disease typically has its onset during the teenage years.

Crohn's disease is an inflammatory condition of unknown cause that mainly affects the end of the small bowel and the beginning of the large bowel, although it may involve the entire gastrointestinal system. Other sites that may be affected include the skin, eyes and joints. Approximately 30 percent of the time, the mouth signs appear before the stomach and bowel lesions. The gastrointestinal involvement leads to complaints of abdominal cramping and pain, nausea and diarrhea. Weight loss and malnutrition may develop, which can lead to decreased red blood cells and decreased growth.

Many different types of mouth lesions have been observed in Crohn's disease. The more common are multiple or separate bumps of the mouth and lips, a so-called cobblestone appearance of the mouth lining, and deep ulcers or holes, especially of the area beneath the gums. Biopsy of the gut lesions and the person's symptoms lead to a correct diagnosis.

Tuberous sclerosis (Bourneville-Pringle syndrome) is uncommon and classically displays mental retardation, seizures and angiofibromas, specific growths on the face. Besides cases of familial origin, this condition can be caused by random, unexplained genetic mutations.

Angiofibromas occur mainly in the crease of tissue next to the nose. Similar bumps can be found next to or under the fingernails. Other types of skin lesions are seen, including a focal area that has a rough surface or that lacks normal skin color. Some patients develop a heart tumor; others may have tumors in the kidneys.

In the mouth, the enamel of the front teeth is often pitted. Another common finding is multiple small bumps on the front gums; they may also be displayed on the lips, inner cheeks, roof of the mouth and tongue. Some patients have enlarged gums as a side effect of medicine taken for seizures; others will have defects in the jaws that can be seen in X-rays. The appearance of the patient establishes the diagnosis.

Extra or Missing Teeth, or Premature Loss of Teeth

* Extra teeth

Extra teeth may be present when the child is born with a cleft lip and/or a cleft palate. One example is cleidocranial dysplasia, a rare genetic bone disorder whose most outstanding characteristic is the absence of a collarbone or one that is deficient on one or both sides. The child tends to be short, with a characteristic facial appearance of wide spaced eyes and prominent forehead. In the mouth, the roof is often narrow and high and cleft palate is often seen. Various dental changes are exhibited. The baby teeth often do not loosen and the adult teeth are delayed in appearing or only partially come through the gum. Many extra teeth may form in the jawbones but fail to erupt into the mouth. X-ray pictures of the jaws will demonstrate characteristic changes besides the abnormal teeth. The diagnosis is based on the above-mentioned signs.

* Missing Teeth

One condition that exhibits missing teeth is hereditary hypohidrotic ectodermal dysplasia, the best known of a group of genetic conditions in which at least two derivatives of the ectoderm (teeth, hair, nails, glands) are deficient in function or absent altogether. Hereditary hypohidrotic ectodermal dysplasia occurs much more often in males. In infancy the baby appears to have an unexplained fever, but actually, the body temperature cannot be controlled in the normal fashion because of a lack or reduced number of sweat glands. Death can occur from this heat intolerance. Other signs include fine, sparse blond hair; this conditions affects not only the head but also the eyebrows and eyelashes. The lips may stick out, as the center of the face is often not fully developed. The nails are often brittle and defective. Within the mouth, there is a lack of saliva due to undeveloped salivary glands and the number of teeth is markedly reduced. The crowns of the teeth are abnormal and often have a cone or pointed shape. These features determine diagnosis.

* Premature loss of teeth

In addition to a traumatic event, jaw infection, or cancer chemotherapy, numerous diseases can result in a premature loss of baby or adult teeth. The list includes diabetes, chronic or cyclical loss of white blood cells, Papillon-Lefevre syndrome, Down syndrome, scurvy, dentin dysplasia, regional odontodysplasia, Langerhans cell disease, leukemia, AIDS and hypophosphatasia.

Hypophosphatasia, a rare, genetic bone disease, is characterized by a lack or reduced amount of alkaline phosphatase, a particular tissue enzyme that is thought to play a role in the production of bone. This disorder is usually diagnosed in infancy although it may not appear until later in childhood or even adulthood. The diagnosis is based on the clinical signs and laboratory tests.

The infantile form usually presents after 6 months of age, when the infant shows a failure to grow. Vomiting and lack of muscle tone may develop. Skeletal malformations reminiscent of rickets appear (e.g., shortened, bowed limbs). Kidney stones also form, as do rib and skull deformities. In the childhood form, a hallmark finding is the premature loss of baby teeth with no apparent infection. The upper and lower front four teeth are usually affected first and may be the only teeth involved. Sometimes the inside of the teeth appears abnormal on an X-ray and the bone around the teeth may be reduced. In X-rays, the skull has an abnormal appearance that has been described as "beaten copper"-it looks like a piece of metal that has been repeatedly hit with a hammer. This look is probably due to thinning of the skull's inner plate of bone.

View Through the Window

Inspection of the mouth, the "window of the body," and its supporting structures is often an excellent, simple way for doctors to identify not only localized dental and gum infections but more generalized body diseases, genetic disorders and conditions. The informed doctor or parent can utilize this information to identify possible serious health problems and to initiate appropriate treatment early, which may lead to a more favorable outcome with fewer complications for the patient.

Michael A. Kahn, DDS, is a Professor of Biologic and Diagnostic Sciences, and Director of the University of Tennessee Oral and Maxillofacial Pathology Diagnostic Services. He is a Fellow and Councilor of the American Academy of Oral and Maxillofacial Pathology and a Diplomate of the American Board of Oral and Maxillofacial Pathology. He is also a charter member of the UT Health Science Center's Academy of Distinguished Teaching Professors.

Jerry E. Bouquot, DDS, MS, is Director of Research of The Maxillofacial Center for Diagnostics & Research and also Director of Head & Neck Diagnostics of America, Morgantown, WE. He is a Fellow of the American Academy of Oral and Maxillofacial Pathology and a Diplomate of the American Board of Oral and Maxillofacial Pathology. He is also a Professor of Dental Medicine at Capital University School of Integrated Medicine, Washington, DC.