Oral Manifestations of Systemic Disease










505
Jaundice, 506
Lipoid Proteinosis, 506
Amyloidosis, 508
Xanthelasma, 508
Scurvy, 508
Iron Deficiency Anemia, 510
Pellagra, 510
Pernicious Anemia, 512
Rickets, 514
Vitamin D–Resistant Rickets, 516
Hypophosphatasia, 516
Hyperparathyroidism, 518
Renal Osteodystrophy, 520
Addison Disease, 520
Diabetes Mellitus, 522
Crohn Disease, 522
Pyostomatitis Vegetans, 524
Uremic Stomatitis, 524
17
Oral Manifestations of
Systemic Disease

506 17 Oral Manifestations of Systemic Disease
Jaundice
Fig. 17.1
Jaundice is the term used to describe increased bilirubin (>3 mg/dL) in the circulation, with higher levels
producing a yellowish cast to the skin and oral mucosa. Bilirubin is the normal breakdown product of
hemoglobin, which is released from degenerating erythrocytes at the end of their 120-day life span.
Hemoglobin is taken up by macrophages, converting it to biliverdin. Biliverdin is then converted to
unconjugated bilirubin, which is lipid soluble and easily absorbed by the cell membranes of hepatocytes.
Hepatocytes convert unconjugated bilirubin to conjugated bilirubin, which is water soluble, and this is
collected in the gallbladder as a component of bile. Bile is then released into the small intestine during
digestion and eventually is excreted in stool.
If the levels of bilirubin in the serum are increased suciently, this compound is deposited in various
tissues, including the skin and sclera. is results in a yellowish color, also known as icterus. is should
not be confused with hypercarotenemia, an increase in levels of carotene, a dietary pigment found in yellow
or orange fruits and vegetables. is may result in a yellow skin color, but it spares the sclera.
Although in some cases elevated bilirubin levels may be normal for a particular individual, the presence
of jaundice should be of some concern, and evaluation to identify the cause should be undertaken. A
variety of hematologic studies should be performed, including determining levels of unconjugated and
conjugated bilirubin. If elevated unconjugated bilirubin levels are found, then conditions that cause premature
destruction of erythrocytes may be responsible, including various hemolytic anemias (autoimmune diseases,
thalassemia, sickle cell anemia) and other erythrocyte abnormalities. If increased levels of conjugated bilirubin
are identied, then conditions that are associated with damage to the liver itself should be considered as
potential causes. Various forms of hepatitis (e.g., viral, alcohol related, other toxins) and cirrhosis, as well
as other problems that may cause biliary obstruction, such as malignancy in this anatomic site, would
result in elevated levels of conjugated bilirubin in the circulation.
erefore, treatment of jaundice is directed at correcting the underlying cause of the elevated bilirubin
levels in the bloodstream.
Lipoid Proteinosis
Figs. 17.2 and 17.3
Lipoid proteinosis, also known as hyalinosis cutis et mucosae, is a rare autosomal recessive disorder that
is caused by mutation of the ECM1 gene, which encodes for extracellular matrix protein 1, a glycoprotein.
Deposition of an acellular, hyalinized material in the vocal cords during infancy causes the baby’s cries to
be hoarse and may lead to initial discovery of the disorder. Later in life, the aected individual will develop
acneiform facial lesions, as well as very small papules along the margins of the eyelids. Eventually the oral
mucosa and skin may develop yellowish, waxy papular and nodular changes. Intraorally, the tongue is
oen aected, in addition to the lips, buccal mucosa, and tonsillar pillars. In some patients, intracranial
calcications may form in the temporal lobes of the brain, and these calcications may be responsible
for seizure disorders that are occasionally experienced. e precise nature of the hyalinized material is
unknown, but it seems to be composed of basement-related compounds, including laminin and types IV
and V collagen.
Genetic counseling is appropriate for parents of persons with this disorder. Treatment is limited to
surgical reduction of those lesions that cause signicant functional problems, such as vocal cord enlargement
that impairs the airway. Surgical recontouring for aesthetic purposes can sometimes be performed, usually
on a limited basis. e life span of these patients is typically not reduced signicantly.

17 Oral Manifestations of Systemic Disease 507
Figure 17.1
Jaundice
Yellow sclera of a patient with sclerosing cholangitis
of the liver.
Figure 17.2
Lipoid Proteinosis
Submucosal nodules of the labial mucosa.
Figure 17.3
Lipoid Proteinosis
Bilateral submucosal nodules of the buccal mucosa.

508 17 Oral Manifestations of Systemic Disease
Amyloidosis
Fig. 17.4
Amyloidosis is a group of conditions that are characterized by the deposition of an insoluble brillary
protein, primarily in the so tissues of the body. Approximately 30 dierent proteins have been associated
with this process, and each type of amyloidosis is associated with a specic protein. Some forms of amyloidosis
are inherited, whereas others are acquired. In all cases the deposits of the protein have a molecular structure
that has been described as a beta pleated sheet arrangement. Because of this stereochemical structure,
Congo red dye preferentially binds to the amyloid material and uniquely will exhibit a glowing apple-green
birefringence when viewed with polarized light, conrming the diagnosis of amyloidosis.
e type of amyloidosis that is most frequently seen intraorally is caused by deposition of monoclonal
light chain components of the immunoglobulin molecule, which are usually produced by abnormal plasma
cells. is presentation is known as AL amyloidosis, and it is oen associated with multiple myeloma.
Diuse deposition within the tongue, producing macroglossia, is the most common oral feature of AL
amyloidosis, but the labial and buccal mucosa also may be involved. In addition, biopsy of labial salivary
glands will oen demonstrate amyloid deposition in cases of systemic amyloidosis.
Aer amyloid is conrmed microscopically, further analysis is required to determine the precise molecular
diagnosis because the various types of amyloidosis have predilections for deposition at dierent sites and
have dierent treatments and prognoses. Patients aected by systemic amyloidosis typically have a poor
prognosis because amyloid accumulates in the heart and kidneys, disrupting the function of these vital
organs and resulting in death.
Xanthelasma
Fig. 17.5
e cutaneous xanthomata comprise a variety of yellowish skin lesions that are characterized by accumula-
tions of lipid-laden macrophages in the supercial dermis. e most common of these conditions is known
as xanthelasma. Xanthelasma develops on the periorbital skin of adults, and the lesions typically present
as bilateral, coalescing, so papules and plaques. e upper eyelid is involved more oen than the lower.
Periorbital amyloid deposits may mimic xanthelasma clinically, but those lesions are rm and are not
yellow.
Treatment usually is initiated for cosmetic reasons. Surgical excision or laser ablation may be performed,
although recurrence of the lesions is rather common.
Some studies have found that aected patients may have hyperlipidemia more frequently than a control-
matched population. erefore, referral of the patient for medical evaluation may be appropriate.
Scurvy
Fig. 17.6
Scurvy is a condition that results from prolonged dietary deciency of vitamin C (ascorbic acid). Vitamin
C is necessary for normal synthesis and maintenance of collagen, a signicant constituent of most connective
tissues. Although scurvy is relatively uncommon today, certain populations are at risk, including autistic
children, alcoholics, psychiatric patients, and the elderly, all of whom may have a limited dietary repertoire.
Patients with gra-versus-host disease may develop scurvy because acidic foods irritate their oral mucosa.
Furthermore, patients with conditions that are associated with iron overload, such as sickle cell anemia
and thalassemia, may acquire this condition because excess iron in the tissues increases the degradation
of vitamin C.
e initial symptoms of scurvy can be nonspecic, including irritability, fatigue, and malaise. With
persistent deciency, perifollicular keratosis, petechial hemorrhages, and joint pain develop. Diuse gingival
hyperplasia with gingival hemorrhage and ulceration is also among the earlier signs of scurvy. Periodontal
bone loss and exfoliation of teeth eventually occur. Subperiosteal hematomas, delayed wound healing, and
ecchymoses caused by minor trauma represent clinical ndings later in the course of disease.
A careful dietary history that demonstrates a signicant lack of vitamin C–rich foods oen will be
highly suggestive of this disease in the appropriate clinical setting. If the diagnosis is in doubt, serum
ascorbic acid levels can be ordered. With vitamin C supplementation, dramatic improvement typically is
seen within a few weeks.

17 Oral Manifestations of Systemic Disease 509
Figure 17.4
Amyloidosis
Firm diffuse swelling of the tongue, resulting in a scalloped
appearance of the lateral borders. (Courtesy Dr. Gregory
Erena.)
Figure 17.5
Xanthelasma
Soft yellow plaques affecting the periorbital skin.
Figure 17.6
Scurvy
Spontaneous gingival hemorrhage with oral mucosal
ecchymoses and hematoma formation. (Courtesy Dr. James
Hargan.)

510 17 Oral Manifestations of Systemic Disease
Iron Deficiency Anemia
Figs. 17.7 and 17.8
Iron deciency anemia is the most common form of anemia, and in the United States, it is estimated that
1% to 2% of adult men and 10% of adult women may be aected. Iron is a necessary component of
oxygen-carrying hemoglobin, and the deciency may result from reduced absorption of iron or increased
demand for iron related to destruction of erythrocytes.
As with any anemia, the signs and symptoms reect the reduced oxygen-carrying capability of the blood,
resulting in fatigue, pallor of the mucous membranes, and shortness of breath. Oral signs and symptoms
include angular cheilitis, atrophy of the dorsal tongue papillae, and burning sensation of the tongue.
e diagnosis of iron deciency anemia is based on hematologic studies, including complete blood
count with erythrocyte parameters, hemoglobin, hematocrit, serum ferritin levels, and iron-binding capacity.
Once the diagnosis is established, the cause should be investigated to determine whether the deciency
is related to dietary factors, iron absorption problems, or increased erythrocyte turnover. Increased erythrocyte
turnover increases demand for iron when erythrocytes are lost through hemorrhage (e.g., gastric ulcer,
ulcerated colon carcinoma, menorrhagia) and have to be replaced. Only aer the specic cause is identied
can appropriate therapy be instituted.
Aer the underlying problem is corrected, iron stores typically have to be restored by administering
supplemental iron, either orally or intravenously.
Pellagra
Fig. 17.9
A deciency of niacin (vitamin B
3
; nicotinic acid) results in the condition known as pellagra. Niacin is an
essential component of nicotinamide adenine dinucleotide (NAD
+
) and nicotinamide adenine dinucleotide
phosphate (NADP
+
), which are critical enzymes for a variety of vital oxidation-reduction reactions. is
vitamin is found in beans, eggs, milk, and vitamin-enriched our, and small amounts are stored in the
liver, although the body can synthesize niacin from dietary tryptophan. erefore, a diet that is decient
in this vitamin will result in pellagra in a relatively short time. e most important features of pellagra are
designated by “the 4 Ds”: diarrhea, dermatitis, dementia, and death. Dementia oen encompasses irritability,
depression, and delusions. e dermatitis that develops is usually more severe in sun-exposed areas.
Stomatitis and glossitis can be noted intraorally, with the tongue appearing erythematous and raw or
smooth.
Although this condition is relatively rare in developed countries, individuals whose diets consist primarily
of corn-based foods, which typically contain minimal niacin and tryptophan, can develop pellagra. Urinary
N-methyl-nicotinamide concentrations will typically be reduced signicantly, conrming the diagnosis.
Treatment consists of oral nicotinamide, which is an amide of niacin that, when taken orally, usually
has fewer gastrointestinal side eects than niacin itself. e pellagra-related dermatitis will typically begin
resolving within a few days aer beginning this therapy.

17 Oral Manifestations of Systemic Disease 511
Figure 17.7
Iron Deficiency Anemia
Bilateral angular cheilitis.
Figure 17.8
Iron Deficiency Anemia
Erythematous patches with blending margins,
affecting the lateral and ventral tongue mucosa.
Figure 17.9
Pellagra
Roughened, scaly skin with hyperpigmentation of sun-exposed areas. The pale band across the dorsum of the
foot was covered by a sandal strap. (Courtesy Dr. Sylvie Brener.)

512 17 Oral Manifestations of Systemic Disease
Pernicious Anemia
Figs. 17.10–17.12
Pernicious anemia is an immune-mediated condition that is characterized by low levels of cobalamin
(vitamin B
12
), which is necessary for nucleic acid synthesis and, therefore, normal cell division. us,
deciency of this vitamin results in impaired hematopoiesis, as well as impacting any tissue that normally
has a rapid turnover, such as the gastrointestinal lining cells. Cobalamin (or extrinsic factor) is found in
foods derived from animals, and it is necessary for normal cell division to take place. Extrinsic factor
binds to intrinsic factor, which is produced by the parietal cells of the stomach lining, and the cobalamin-
intrinsic factor complex is preferentially absorbed by the lining cells of the small intestine, aer which it
is disseminated throughout the body by the bloodstream. Autoantibodies directed against the parietal cells
and intrinsic factor result in inhibition of cobalamin absorption, and with reduced levels of this critical
molecule, there is impaired mitotic activity of the hematopoietic cells. e hematopoietic cells that are
produced appear abnormal and include hypersegmented neutrophils and enlarged erythrocytes. e term
megaloblastic anemia is applied to this condition because of these large erythrocytes (which are also seen
in folate deciency).
e initial symptoms of pernicious anemia usually include fatigue, weakness, and shortness of breath,
but eventually neurologic symptoms, such as symmetric paresthesias and numbness, develop. Central
nervous system involvement may also eventuate in diculty walking and dementia.
Oral signs and symptoms may include neurologic components, such as oral mucosal pain or a burning
sensation. is may be accompanied by red macular patches and atrophic glossitis.
Evaluation of a patient suspected of having pernicious anemia includes a complete blood count with
erythrocyte parameters. If a megaloblastic anemia is identied, then serum cobalamin and folate levels
can be ordered. If serum cobalamin levels are low, then anti-parietal cell and anti-intrinsic factor antibody
assays should be obtained. Although anti-parietal cell antibodies may be found in as high as 90% of patients
with pernicious anemia, they are not specic, because they can be found in a number of other autoimmune
diseases as well. Anti-intrinsic factor antibodies are found in approximately 70% of aected patients, and
they are quite specic for pernicious anemia.
Treatment generally consists of intramuscular injections of cobalamin at regular intervals because the
presence of intrinsic factor antibodies in the gastrointestinal tract could inhibit absorption. Some studies
have found that large doses of cobalamin given orally can overcome the lack of intrinsic factor because
of the overwhelming concentration of the vitamin. It is important to distinguish pernicious anemia from
folate deciency because folate supplementation will improve the hematologic status but the neurologic
issues associated with pernicious anemia will worsen. Monitoring these patients for gastric carcinoma is
prudent because some studies have suggested that the incidence of this malignancy is increased in the
areas of atrophic gastritis that develop in pernicious anemia.

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505Jaundice, 506Lipoid Proteinosis, 506Amyloidosis, 508Xanthelasma, 508Scurvy, 508Iron Deficiency Anemia, 510Pellagra, 510Pernicious Anemia, 512Rickets, 514Vitamin D–Resistant Rickets, 516Hypophosphatasia, 516Hyperparathyroidism, 518Renal Osteodystrophy, 520Addison Disease, 520Diabetes Mellitus, 522Crohn Disease, 522Pyostomatitis Vegetans, 524Uremic Stomatitis, 52417 Oral Manifestations of Systemic Disease 506 17 Oral Manifestations of Systemic Disease JaundiceFig. 17.1Jaundice is the term used to describe increased bilirubin (>3 mg/dL) in the circulation, with higher levels producing a yellowish cast to the skin and oral mucosa. Bilirubin is the normal breakdown product of hemoglobin, which is released from degenerating erythrocytes at the end of their 120-day life span. Hemoglobin is taken up by macrophages, converting it to biliverdin. Biliverdin is then converted to unconjugated bilirubin, which is lipid soluble and easily absorbed by the cell membranes of hepatocytes. Hepatocytes convert unconjugated bilirubin to conjugated bilirubin, which is water soluble, and this is collected in the gallbladder as a component of bile. Bile is then released into the small intestine during digestion and eventually is excreted in stool.If the levels of bilirubin in the serum are increased suciently, this compound is deposited in various tissues, including the skin and sclera. is results in a yellowish color, also known as icterus. is should not be confused with hypercarotenemia, an increase in levels of carotene, a dietary pigment found in yellow or orange fruits and vegetables. is may result in a yellow skin color, but it spares the sclera.Although in some cases elevated bilirubin levels may be normal for a particular individual, the presence of jaundice should be of some concern, and evaluation to identify the cause should be undertaken. A variety of hematologic studies should be performed, including determining levels of unconjugated and conjugated bilirubin. If elevated unconjugated bilirubin levels are found, then conditions that cause premature destruction of erythrocytes may be responsible, including various hemolytic anemias (autoimmune diseases, thalassemia, sickle cell anemia) and other erythrocyte abnormalities. If increased levels of conjugated bilirubin are identied, then conditions that are associated with damage to the liver itself should be considered as potential causes. Various forms of hepatitis (e.g., viral, alcohol related, other toxins) and cirrhosis, as well as other problems that may cause biliary obstruction, such as malignancy in this anatomic site, would result in elevated levels of conjugated bilirubin in the circulation.erefore, treatment of jaundice is directed at correcting the underlying cause of the elevated bilirubin levels in the bloodstream.Lipoid ProteinosisFigs. 17.2 and 17.3Lipoid proteinosis, also known as hyalinosis cutis et mucosae, is a rare autosomal recessive disorder that is caused by mutation of the ECM1 gene, which encodes for extracellular matrix protein 1, a glycoprotein. Deposition of an acellular, hyalinized material in the vocal cords during infancy causes the baby’s cries to be hoarse and may lead to initial discovery of the disorder. Later in life, the aected individual will develop acneiform facial lesions, as well as very small papules along the margins of the eyelids. Eventually the oral mucosa and skin may develop yellowish, waxy papular and nodular changes. Intraorally, the tongue is oen aected, in addition to the lips, buccal mucosa, and tonsillar pillars. In some patients, intracranial calcications may form in the temporal lobes of the brain, and these calcications may be responsible for seizure disorders that are occasionally experienced. e precise nature of the hyalinized material is unknown, but it seems to be composed of basement-related compounds, including laminin and types IV and V collagen.Genetic counseling is appropriate for parents of persons with this disorder. Treatment is limited to surgical reduction of those lesions that cause signicant functional problems, such as vocal cord enlargement that impairs the airway. Surgical recontouring for aesthetic purposes can sometimes be performed, usually on a limited basis. e life span of these patients is typically not reduced signicantly. 17 Oral Manifestations of Systemic Disease 507■ Figure 17.1 Jaundice Yellow sclera of a patient with sclerosing cholangitis of the liver. ■ Figure 17.2 Lipoid Proteinosis Submucosal nodules of the labial mucosa. ■ Figure 17.3 Lipoid Proteinosis Bilateral submucosal nodules of the buccal mucosa. 508 17 Oral Manifestations of Systemic Disease AmyloidosisFig. 17.4Amyloidosis is a group of conditions that are characterized by the deposition of an insoluble brillary protein, primarily in the so tissues of the body. Approximately 30 dierent proteins have been associated with this process, and each type of amyloidosis is associated with a specic protein. Some forms of amyloidosis are inherited, whereas others are acquired. In all cases the deposits of the protein have a molecular structure that has been described as a beta pleated sheet arrangement. Because of this stereochemical structure, Congo red dye preferentially binds to the amyloid material and uniquely will exhibit a glowing apple-green birefringence when viewed with polarized light, conrming the diagnosis of amyloidosis.e type of amyloidosis that is most frequently seen intraorally is caused by deposition of monoclonal light chain components of the immunoglobulin molecule, which are usually produced by abnormal plasma cells. is presentation is known as AL amyloidosis, and it is oen associated with multiple myeloma. Diuse deposition within the tongue, producing macroglossia, is the most common oral feature of AL amyloidosis, but the labial and buccal mucosa also may be involved. In addition, biopsy of labial salivary glands will oen demonstrate amyloid deposition in cases of systemic amyloidosis.Aer amyloid is conrmed microscopically, further analysis is required to determine the precise molecular diagnosis because the various types of amyloidosis have predilections for deposition at dierent sites and have dierent treatments and prognoses. Patients aected by systemic amyloidosis typically have a poor prognosis because amyloid accumulates in the heart and kidneys, disrupting the function of these vital organs and resulting in death.XanthelasmaFig. 17.5e cutaneous xanthomata comprise a variety of yellowish skin lesions that are characterized by accumula-tions of lipid-laden macrophages in the supercial dermis. e most common of these conditions is known as xanthelasma. Xanthelasma develops on the periorbital skin of adults, and the lesions typically present as bilateral, coalescing, so papules and plaques. e upper eyelid is involved more oen than the lower. Periorbital amyloid deposits may mimic xanthelasma clinically, but those lesions are rm and are not yellow.Treatment usually is initiated for cosmetic reasons. Surgical excision or laser ablation may be performed, although recurrence of the lesions is rather common.Some studies have found that aected patients may have hyperlipidemia more frequently than a control-matched population. erefore, referral of the patient for medical evaluation may be appropriate.ScurvyFig. 17.6Scurvy is a condition that results from prolonged dietary deciency of vitamin C (ascorbic acid). Vitamin C is necessary for normal synthesis and maintenance of collagen, a signicant constituent of most connective tissues. Although scurvy is relatively uncommon today, certain populations are at risk, including autistic children, alcoholics, psychiatric patients, and the elderly, all of whom may have a limited dietary repertoire. Patients with gra-versus-host disease may develop scurvy because acidic foods irritate their oral mucosa. Furthermore, patients with conditions that are associated with iron overload, such as sickle cell anemia and thalassemia, may acquire this condition because excess iron in the tissues increases the degradation of vitamin C.e initial symptoms of scurvy can be nonspecic, including irritability, fatigue, and malaise. With persistent deciency, perifollicular keratosis, petechial hemorrhages, and joint pain develop. Diuse gingival hyperplasia with gingival hemorrhage and ulceration is also among the earlier signs of scurvy. Periodontal bone loss and exfoliation of teeth eventually occur. Subperiosteal hematomas, delayed wound healing, and ecchymoses caused by minor trauma represent clinical ndings later in the course of disease.A careful dietary history that demonstrates a signicant lack of vitamin C–rich foods oen will be highly suggestive of this disease in the appropriate clinical setting. If the diagnosis is in doubt, serum ascorbic acid levels can be ordered. With vitamin C supplementation, dramatic improvement typically is seen within a few weeks. 17 Oral Manifestations of Systemic Disease 509■ Figure 17.4 Amyloidosis Firm diffuse swelling of the tongue, resulting in a scalloped appearance of the lateral borders. (Courtesy Dr. Gregory Erena.)■ Figure 17.5 Xanthelasma Soft yellow plaques affecting the periorbital skin. ■ Figure 17.6 Scurvy Spontaneous gingival hemorrhage with oral mucosal ecchymoses and hematoma formation. (Courtesy Dr. James Hargan.) 510 17 Oral Manifestations of Systemic Disease Iron Deficiency AnemiaFigs. 17.7 and 17.8Iron deciency anemia is the most common form of anemia, and in the United States, it is estimated that 1% to 2% of adult men and 10% of adult women may be aected. Iron is a necessary component of oxygen-carrying hemoglobin, and the deciency may result from reduced absorption of iron or increased demand for iron related to destruction of erythrocytes.As with any anemia, the signs and symptoms reect the reduced oxygen-carrying capability of the blood, resulting in fatigue, pallor of the mucous membranes, and shortness of breath. Oral signs and symptoms include angular cheilitis, atrophy of the dorsal tongue papillae, and burning sensation of the tongue.e diagnosis of iron deciency anemia is based on hematologic studies, including complete blood count with erythrocyte parameters, hemoglobin, hematocrit, serum ferritin levels, and iron-binding capacity. Once the diagnosis is established, the cause should be investigated to determine whether the deciency is related to dietary factors, iron absorption problems, or increased erythrocyte turnover. Increased erythrocyte turnover increases demand for iron when erythrocytes are lost through hemorrhage (e.g., gastric ulcer, ulcerated colon carcinoma, menorrhagia) and have to be replaced. Only aer the specic cause is identied can appropriate therapy be instituted.Aer the underlying problem is corrected, iron stores typically have to be restored by administering supplemental iron, either orally or intravenously.PellagraFig. 17.9A deciency of niacin (vitamin B3; nicotinic acid) results in the condition known as pellagra. Niacin is an essential component of nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+), which are critical enzymes for a variety of vital oxidation-reduction reactions. is vitamin is found in beans, eggs, milk, and vitamin-enriched our, and small amounts are stored in the liver, although the body can synthesize niacin from dietary tryptophan. erefore, a diet that is decient in this vitamin will result in pellagra in a relatively short time. e most important features of pellagra are designated by “the 4 Ds”: diarrhea, dermatitis, dementia, and death. Dementia oen encompasses irritability, depression, and delusions. e dermatitis that develops is usually more severe in sun-exposed areas.Stomatitis and glossitis can be noted intraorally, with the tongue appearing erythematous and raw or smooth.Although this condition is relatively rare in developed countries, individuals whose diets consist primarily of corn-based foods, which typically contain minimal niacin and tryptophan, can develop pellagra. Urinary N-methyl-nicotinamide concentrations will typically be reduced signicantly, conrming the diagnosis.Treatment consists of oral nicotinamide, which is an amide of niacin that, when taken orally, usually has fewer gastrointestinal side eects than niacin itself. e pellagra-related dermatitis will typically begin resolving within a few days aer beginning this therapy. 17 Oral Manifestations of Systemic Disease 511■ Figure 17.7 Iron Deficiency Anemia Bilateral angular cheilitis. ■ Figure 17.8 Iron Deficiency Anemia Erythematous patches with blending margins, affecting the lateral and ventral tongue mucosa. ■ Figure 17.9 Pellagra Roughened, scaly skin with hyperpigmentation of sun-exposed areas. The pale band across the dorsum of the foot was covered by a sandal strap. (Courtesy Dr. Sylvie Brener.) 512 17 Oral Manifestations of Systemic Disease Pernicious AnemiaFigs. 17.10–17.12Pernicious anemia is an immune-mediated condition that is characterized by low levels of cobalamin (vitamin B12), which is necessary for nucleic acid synthesis and, therefore, normal cell division. us, deciency of this vitamin results in impaired hematopoiesis, as well as impacting any tissue that normally has a rapid turnover, such as the gastrointestinal lining cells. Cobalamin (or extrinsic factor) is found in foods derived from animals, and it is necessary for normal cell division to take place. Extrinsic factor binds to intrinsic factor, which is produced by the parietal cells of the stomach lining, and the cobalamin-intrinsic factor complex is preferentially absorbed by the lining cells of the small intestine, aer which it is disseminated throughout the body by the bloodstream. Autoantibodies directed against the parietal cells and intrinsic factor result in inhibition of cobalamin absorption, and with reduced levels of this critical molecule, there is impaired mitotic activity of the hematopoietic cells. e hematopoietic cells that are produced appear abnormal and include hypersegmented neutrophils and enlarged erythrocytes. e term megaloblastic anemia is applied to this condition because of these large erythrocytes (which are also seen in folate deciency).e initial symptoms of pernicious anemia usually include fatigue, weakness, and shortness of breath, but eventually neurologic symptoms, such as symmetric paresthesias and numbness, develop. Central nervous system involvement may also eventuate in diculty walking and dementia.Oral signs and symptoms may include neurologic components, such as oral mucosal pain or a burning sensation. is may be accompanied by red macular patches and atrophic glossitis.Evaluation of a patient suspected of having pernicious anemia includes a complete blood count with erythrocyte parameters. If a megaloblastic anemia is identied, then serum cobalamin and folate levels can be ordered. If serum cobalamin levels are low, then anti-parietal cell and anti-intrinsic factor antibody assays should be obtained. Although anti-parietal cell antibodies may be found in as high as 90% of patients with pernicious anemia, they are not specic, because they can be found in a number of other autoimmune diseases as well. Anti-intrinsic factor antibodies are found in approximately 70% of aected patients, and they are quite specic for pernicious anemia.Treatment generally consists of intramuscular injections of cobalamin at regular intervals because the presence of intrinsic factor antibodies in the gastrointestinal tract could inhibit absorption. Some studies have found that large doses of cobalamin given orally can overcome the lack of intrinsic factor because of the overwhelming concentration of the vitamin. It is important to distinguish pernicious anemia from folate deciency because folate supplementation will improve the hematologic status but the neurologic issues associated with pernicious anemia will worsen. Monitoring these patients for gastric carcinoma is prudent because some studies have suggested that the incidence of this malignancy is increased in the areas of atrophic gastritis that develop in pernicious anemia. 17 Oral Manifestations of Systemic Disease 513■ Figure 17.10 Pernicious Anemia Erythematous patches with ill-defined borders affecting the right lateral tongue. ■ Figure 17.11 Pernicious Anemia Same patient as Fig. 17.10, showing a similar erythematous patch affecting the left lateral tongue. Such lesions are often multiple and can affect any oral mucosal site. ■ Figure 17.12 Pernicious Anemia Erythematous patch involving the maxillary labial mucosa. 514 17 Oral Manifestations of Systemic Disease RicketsFigs. 17.13–17.15Inadequate vitamin D levels during the early years of development lead to the condition known as rickets. e manifestations of this disorder initially may be noted by age 2 or 3 years, when aected children develop widened, enlarged epiphyseal plates throughout the skeleton because the trabeculae of osteoid that are forming in these areas lacks calcium for appropriate mineralization. Because vitamin D is necessary for absorption of calcium from the gut, inadequate vitamin D results in reduced calcium in the bloodstream, which impacts the developing calcied structures of the body, including the teeth. Calcium metabolism and the role that vitamin D plays in maintaining appropriate calcium levels in the body represent a complex array of checks and balances. Most investigators classify vitamin D as a hormone rather than a true vitamin. In most instances, vitamin D deciency is not related to diet, because the precursor is produced in the skin by the action of ultraviolet light on 7-dehydrocholesterol. is results in formation of previtamin D3, which is then converted to vitamin D3 (cholecalciferol). In the liver, vitamin D3 is transformed to 25-hydroxy-vitamin D3 (25-OH-vitamin D3), which is then altered in the cells of the kidney to its nal active form, 1α,25-dihydroxy-vitamin D3. Active vitamin D3 is necessary for absorption of calcium from the gut and interacts with parathyroid hormone to ensure that proper levels of calcium are present in the bloodstream.In most cases of rickets, lack of adequate sun exposure leads to reduced levels of vitamin D. Factors such as dark skin (melanin absorbs ultraviolet [UV] light), illness that requires connement indoors, higher latitudes geographically, and garments that cover most of the skin contribute to vitamin D deciency. In most developed countries, milk and cereal are fortied with vitamin D, although rickets may develop in children who are exclusively breast-fed for an extended period of time and do not receive adequate sunlight exposure.Reduced calcium absorption results in poorly calcied osteoid in developing bone, and the resulting bone is quite weak. When the child begins to walk, either bowing or “knock-kneed” distortion of the legs develops. Hypotonia and muscle weakness, both of which are related to decreased serum calcium, also signal vitamin D deciency. Active growth centers of the skeleton are enlarged, resulting in prominent swellings of the costochondral junctions (so-called rachitic rosary, because it resembles a string of beads draped on the chest). e anterior fontanelle of the skull oen remains open in infants with rickets. Vitamin D deciency during early childhood, when the teeth are developing, causes signicant hypocalcied defects in the teeth.Treatment consists of daily oral supplementation with cholecalciferol. If calcium deciency appears to be contributing to the patient’s rickets, calcium supplements should also be administered. 17 Oral Manifestations of Systemic Disease 515■ Figure 17.13 Rickets Enamel hypoplasia in a patient affected by rickets. In this case the child had been exclusively breast-fed and had little exposure to sunlight. (Courtesy Dr. Pamela McDonald.)■ Figure 17.14 Rickets Radiograph of the same patient in Fig. 17.13 identifying enamel hypoplasia of the central incisors. The enamel of these teeth is formed early in childhood and therefore was most affected by the dietary vitamin D deficiency. (Courtesy Dr. Pamela McDonald.)■ Figure 17.15 Rickets Radiograph of the same patient in Fig. 17.13 showing enamel hypoplasia and hypocal-cification of the crown of the mandibular permanent first molar. (Courtesy Dr. Pamela McDonald.) 516 17 Oral Manifestations of Systemic Disease Vitamin D–Resistant RicketsFigs. 17.16 and 17.17Vitamin D–resistant rickets (VDRR), also known as familial hypophosphatemic rickets, represents a group of heritable conditions that are characterized by loss of phosphate in the urine (leading to reduced serum phosphate levels), low to normal vitamin D levels, and elevated levels of FGF23 (broblast growth factor 23). Patients develop many of the signs of rickets, including bowing of the lower limbs in childhood, reduced height, and bone pain. Most cases of VDRR are inherited as an X-linked dominant trait, caused by mutation of the PHEX (phosphate-regulating gene with endopeptidase activity on the X chromosome) gene. When PHEX is mutated, levels of FGF23 are increased, and this increases the loss of phosphate by the kidney. X-linked dominant VDRR occurs with a frequency of 1 in 20,000, but less common autosomal dominant and recessive forms are also described and involve mutations of dierent genes.e oral ndings are signicant because the dentition exhibits a variety of abnormalities, including thin enamel and defects in the dentin that may extend to the dentinoenamel junction. An ill-dened lamina dura is oen seen radiographically, as well as abbreviated roots. e teeth have enlarged pulp chambers, and the lengthened pulp horns reach into the cusps of the teeth. is results in susceptibility of the teeth to pulpal exposure and necrosis, either spontaneous or caused by attrition and abrasion. e nonvital teeth develop periapical inammation that results in abscess formation and multiple sinus tracts. is can be puzzling for the clinician because the teeth are not carious. Some investigators also have suggested that periodontitis is more prevalent and severe in patients aected by VDRR.Treatment of the skeletal manifestations of VDRR includes administration of oral phosphate supplements in conjunction with calcitriol, the active form of vitamin D. is therapy improves some of the serologic parameters, but modest impact on growth and development is usually seen, and some patients may not respond at all.Management of the dental problems includes careful periodic clinical and radiographic examination, and dental sealants have been recommended by some investigators to prevent pulpal exposure. Endodontic treatment of teeth showing signs of pulpal necrosis or periapical inammatory disease also is recommended. Full crown restorations may be challenging because of the reduced amount of dentin that comprises the crowns of the teeth. With respect to periodontitis, studies have found that adult VDRR patients who have taken phosphate and active vitamin D supplements from the time of childhood seem to have less periodontal destruction.HypophosphatasiaFig. 17.18Hypophosphatasia represents a group of heritable disorders that are characterized by a decrease in tissue nonspecic alkaline phosphatase. Both autosomal dominant and autosomal recessive inheritance patterns have been described, and because of the variety of mutations responsible for this condition, the spectrum of clinical features and severity of involvement is wide ranging. Detailed discussion of each of these varieties—odontohypophosphatasia, adult, childhood, infantile, perinatal, pseudohypophosphatasia, and benign prenatal hypophosphatasia—is beyond the scope of this text.Odontohypophosphatasia is probably the most common variant and has the least impact on the overall health of the patient. Aected individuals experience premature loss of the deciduous dentition, typically the incisor teeth. No other signicant problems arise, and a normal life span is expected. Perinatal and infantile hypophosphatasia are serious conditions that appear early in life. Perinatal hypophosphatasia is evident at birth, and severe hypomineralization of the skeleton is present. ese patients typically die soon aer birth. Infantile hypophosphastasia can be identied by 6 months of age and is characterized by skeletal deformities related to hypomineralization of bone. Approximately 50% mortality can be expected. e childhood form of hypophosphatasia is typically identied aer 6 months of age and can show a range of expression from mild to severe. In the severe form, there is premature loss of all of the deciduous dentition, whereas with mild cases only a few teeth are lost prematurely. Many of the skeletal features seen in rickets may be evident in severe examples.Diagnosis of hypophosphatasia depends on identifying decreased serum alkaline phosphatase in the appropriate clinical setting (medical history, physical examination, routine laboratory ndings, radiographic features). Because alkaline phosphatase levels vary during life, age- and sex-adjusted reference ranges should be used. Blood and urine samples can be tested for increased phosphoethanolamine, which is another feature of hypophosphatasia. Deciduous teeth that are shed prematurely can be examined histo-pathologically for evidence of reduced or absent cementum. 17 Oral Manifestations of Systemic Disease 517■ Figure 17.16 Vitamin D–Resistant Rickets Widened, elongated pulp chambers characteristic of vitamin D–resistant rickets. Note the teeth that have become nonvital due to this condition, necessitating endodontic therapy. (Courtesy Dr. Pamela McDonald.)■ Figure 17.17 Vitamin D–Resistant Rickets The widened, elongated pulp chambers often extend far into the coronal portion of the dentin, increasing the risk of pulpal exposure related to minor trauma. (Courtesy Dr. Pamela McDonald.)■ Figure 17.18 Hypophosphatasia Premature loss of the mandibular anterior dentition. 518 17 Oral Manifestations of Systemic Disease Management consists of genetic counseling for the parents and patient. Treatment is essentially focused on symptomatic care, such as orthopedic surgery to help correct skeletal deformities and fractures. Prosthetic replacement of lost dentition is also appropriate.HyperparathyroidismFigs. 17.19–17.22Excess parathyroid hormone production, whether autonomous or physiologic, is termed hyperparathyroidism (HPT). Primary HPT represents autonomous production of parathyroid hormone, usually by a parathyroid adenoma (80% to 85% of cases), although parathyroid hyperplasia (10% to 15%) or parathyroid carcinoma (1%) may be responsible. A physiologic reason for HPT is seen in patients with end-stage renal disease because they typically have low serum calcium levels. e low calcium levels are related to loss of calcium by the kidney and lack of absorption of calcium from the gut, the latter caused by lack of production of active vitamin D by damaged kidneys. is parathyroid hormone production that is stimulated by low calcium levels is termed secondary HPT. Parathyroid hormone interacts with osteoblasts to stimulate the dierentiation of osteoclasts. e osteoclasts then resorb bone, releasing calcium into the bloodstream. Under such continuous stimulation, the parathyroid glands usually become hyperplastic, and occasionally they can develop into autonomously functioning adenomas. is condition is termed tertiary HPT, and it is usually identied aer the patient is treated by kidney transplantation and the calcium levels do not return to normal.Most cases of HPT are asymptomatic and are identied by routine laboratory studies that are ordered during annual physical examinations, usually in patients older than 60 years. ere are signs and symptoms of this condition that are considered characteristic, including the ndings of “stones, bones, and abdominal groans,” referring to increased prevalence of renal calculi (kidney stones); a variety of osseous alterations, such as brown tumors of bone; and duodenal ulcers.Radiographic changes seen in the jaws include generalized loss of the lamina dura, which represents one of the rst skeletal changes seen with imaging studies. e terminal phalanges are also aected early in this process. e trabecular pattern of the bone oen takes on a ne opaque appearance that has been described as a “ground-glass” pattern. Brown tumors tend to occur later in the course of this disorder and can cause a radiolucent defect in any bone, including the jaws. ese lesions represent a reactive process composed of vascular granulation-type tissue, osteoclast-type giant cells, and abundant hemorrhage with hemosiderin. e formalin-xed erythrocytes and hemosiderin have a brown color, thus the term “brown tumor.”Treatment of primary or tertiary HPT consists of surgical removal of the oending lesional parathyroid tissue, which is identied by means of a nuclear medicine imaging study termed a sestamibi scan. Secondary HPT is treated with calcium supplements, active vitamin D analogues, and non–calcium phosphate binders, which reduce serum phosphate levels. At times, surgical excision of hyperplastic parathyroid glands also is necessary in this situation.■ Figure 17.19 Hyperparathyroidism Initial presentation of a patient with a parathyroid adenoma that was producing parathyroid hormone. The left facial swelling is caused by an intraoral mass, representing a brown tumor of hyperparathyroidism. 17 Oral Manifestations of Systemic Disease 519■ Figure 17.20 Hyperparathyroidism A panoramic radiograph of the same patient seen in Fig. 17.19 demonstrating an ill-defined radiolucency of the left body of the mandible. Biopsy showed a giant cell lesion, and serologic studies identified increased levels of parathyroid hormone produced by a parathyroid adenoma. ■ Figure 17.21 Hyperparathyroidism Same patient as in Fig. 17.20 showing an ulcerated mass that represents a parathyroid adenoma-related brown tumor of hyperparathyroidism that has broken out of bone. ■ Figure 17.22 Hyperparathyroidism Same patient as in Fig. 17.20 several weeks after removal of the parathyroid adenoma, showing intact oral mucosa and reduction in the size of the lesion. 520 17 Oral Manifestations of Systemic Disease Renal OsteodystrophyFigs. 17.23 and 17.24Renal osteodystrophy (ROD) is a signicant and common complication of chronic kidney disease (CKD), and just one component of CKD mineral bone disorder (MBD). e pathogenesis of ROD is complex, involving abnormal interactions and imbalances among parathyroid hormone, vitamin D metabolites, serum calcium and phosphate levels, the kidneys, and broblast growth factor 23, resulting in the disruption of normal bone physiology. Aected children will show stunted growth and distortion of the long bones, and adults will have an increased incidence of fractures, in addition to expansion of aected bones.Involvement of the facial bones by ROD is frequently observed, but the extent can vary considerably. ese lesions usually have a high rate of turnover of the osseous tissue. In early cases, a “salt and pepper” radiographic pattern may develop due to scattered foci of osteoclastic activity and osteoblastic activity. is pattern is particularly evident in skull lms. e marrow spaces are usually replaced by brous connective tissue, and the term osteitis brosa cystica has been applied to the radiographic changes, although the “cystica” portion of the name refers only to the areas of bone resorption and not true cyst formation. Other patients may develop a diuse, ground-glass appearance of the bone, including resorption of the lamina dura, as described with hyperparathyroidism. A smaller percentage of patients, most of whom have had poorly controlled CKD, will develop osseous expansion, characterized by diuse enlargement of the jaws. Although historically this has been termed leontiasis ossea (literally “lion bones”), some investigators have suggested that a more appropriate term would be expansive renal osteitis brosa.Renal transplant is the ideal treatment for this condition, but a lack of matched donors and previous failed transplants are signicant barriers. Patients are usually managed by administering a reduced-phosphate diet, calcium-free phosphate binders, and active vitamin D supplementation in an attempt to correct the serologic balance between calcium and phosphate ions.Addison DiseaseFig. 17.25Addison disease, also known as hypoadrenocortism or primary adrenal insuciency, is a condition that is characterized by destruction of the adrenal cortex, with subsequent reduction in the production of steroid hormones. Prior to the synthesis of cortisone by biochemists in 1949, this disease was uniformly fatal. In industrialized countries, 80% to 90% of cases are caused by autoimmune attack of the glandular tissue, but in less developed parts of the world, tuberculosis is the principal cause. Although heritable conditions can result in adrenal hypofunction, these are rare; nevertheless, if Addison disease occurs in a child, genetic causes should be considered.e initial manifestations of Addison disease can be quite nonspecic, and delayed diagnosis of this condition is common. e reduced production of glucocorticoid and mineralocorticoid hormones results initially in signs and symptoms that are rather nonspecic, including fatigue, vomiting, loss of appetite, weight loss, and abdominal pain. If salt craving or increased skin pigmentation (“bronzing” of the skin) are among the early symptoms, these may suggest the diagnosis. Pigmentation occurs because circulating steroid levels are reduced, and the anterior pituitary is stimulated to produce adrenocorticotropic hormone (ACTH). ACTH also reacts with a receptor on melanocytes to stimulate melanin production. Oral pigmenta-tion also may develop, primarily aecting the lips, buccal mucosa, and gingiva. e diagnosis is conrmed by the standard-dose corticotropin test, by which synthetic ACTH is injected and the cortisol level is measured. If no signicant rise in cortisol production is seen, the diagnosis of primary Addison disease is conrmed.If the condition is not diagnosed, the patient may experience acute adrenal insuciency, also known as an addisonian crisis, which is a life-threatening event. is may develop while the patient is under treatment as well, and typically is identied when the patient experiences symptoms of vomiting, abdominal pain, severe hypotension, and shock. is represents a medical emergency and should be managed in the hospital.Treatment consists of lifelong hormone replacement therapy, including a glucocorticoid, such as hydrocortisone, potentially combined with a mineralocorticoid, such as udrocortisone. Because the adrenal cortex normally is responsible for all of the androgenic hormone production in women, those women who have reduced libido or symptoms of depression may benet from treatment with an androgen, such as dehydroepiandrosterone (DHEA). Careful monitoring of the hormone levels and routine blood parameters is necessary, and hydrocortisone should be increased during periods of stress, such as during signicant illness or major surgery. 17 Oral Manifestations of Systemic Disease 521■ Figure 17.23 Renal Osteodystrophy Expansion of the maxilla in a patient with renal osteodystrophy, resulting in a bony hard, bulging palatal mass. ■ Figure 17.24 Renal Osteodystrophy Radiograph demonstrating the fine, ground-glass pattern associated with renal osteodystrophy. Note the loss of lamina dura around the teeth. ■ Figure 17.25 Addison Disease Diffuse brown pigmentation of the attached gingiva in a white patient with Addison disease. 522 17 Oral Manifestations of Systemic Disease Diabetes MellitusFig. 17.26Diabetes mellitus (DM) is considered to be a group of disorders that are caused by altered carbohydrate metabolism, resulting in chronically elevated levels of blood glucose (hyperglycemia). Most cases of DM are related to either a decrease in insulin production (type 1 DM, representing 5% to 10% of all diabetics) or a reduced impact of insulin on the target tissues, known as insulin resistance (type 2 DM). Type 1 DM is oen caused by immunologic attack of the insulin-producing beta cells of the pancreatic islets, whereas type 2 DM is usually associated with obesity. An in-depth discussion of DM is beyond the scope of this text. However, the impact of this common systemic disease is tremendous, as reected in the fact that its complications are the leading cause of end-stage kidney disease, adult blindness, and lower limb amputations that are not related to trauma. Signicant acceleration of peripheral vascular disease and coronary artery disease is associated with this condition, as well as susceptibility to infection. e diagnosis is based on fasting blood glucose levels, glucose tolerance testing, and levels of hemoglobin A1c (glycated hemoglobin).Although no oral lesions that are specic for DM are currently recognized, many authors have identied oral mucosal and periodontal alterations that seem to be more prevalent and more severe in patients with DM. Periodontitis is seen more frequently in DM, and the severity is usually worse than in a non-DM control population. Gingival inammation also appears to be more pronounced in diabetic patients, compared with nondiabetic patients with similar plaque control. Modest improvements in the hemoglobin A1c levels of diabetic patients have been shown when their periodontitis is treated and gingival health is maintained.Crohn DiseaseFigs. 17.27 and 17.28Crohn disease (CD), also known as regional ileitis, is an inammatory bowel disease of uncertain etiology. e condition is seen primarily in industrialized countries and can present at any age, although two peaks in frequency—the second to third decade and the sixth decade—are identied in most large series. Although the most common site of involvement with CD is the terminal segment of the ileum, any portion of the gastrointestinal tract, from the mouth to the anus, can be aected.Patients may have nonspecic signs and symptoms, including abdominal cramping, diarrhea, nausea, weight loss, vomiting, and fever. Persistence of these problems will usually trigger investigation to rule out CD.Oral lesions are found in some patients with CD, although the precise frequency is dicult to assess because CD patients can also develop common oral lesions that may not be related to their systemic disease. In addition, the oral lesions may develop prior to the diagnosis of CD. A variety of oral mucosal alterations have been described, including ulcers, a “cobble-stone” appearance of the mucosa, swelling of the lips, mucosal tags, and erythematous enlargement of the gingivae. Some investigators have described the oral ulcers as resembling aphthous ulcerations. In many cases the ulcers have a linear, ssured congura-tion, lying at the depth of the buccal vestibule, and these seem to be more suggestive of CD. Parallel hyperplastic folds of tissue that resemble epulis ssuratum have also been described in the buccal vestibules of these patients. In addition, pyostomatitis vegetans (see next topic) may develop in CD, but this uncommon condition is more frequently associated with ulcerative colitis.Histopathologic ndings are characteristic but not pathognomonic. Nonnecrotizing granulomatous inammation may be found, although this is not identied in every gastrointestinal biopsy sample. Oen the granulomatous inammation will be seen in biopsies of the oral lesions. e diagnosis of CD is based primarily on the clinical presentation, combined with endoscopic, histopathologic, and radiologic ndings. Serologic studies are oen helpful in ruling out other conditions, but no specic tests are diagnostic for CD.Medical treatment is generally used initially, with systemic corticosteroids being given to suppress the abnormal inammatory process, followed by a variety of dierent classes of medication designed to maintain remission. Most patients with CD will eventually require surgery for resection of an involved bowel segment that has developed a stricture or for correction of a cutaneous or vaginal stula. 17 Oral Manifestations of Systemic Disease 523■ Figure 17.26 Diabetes Mellitus Bright red, hyperplastic gingival lesions, characteristic of poorly controlled diabetes mellitus. ■ Figure 17.27 Crohn Disease Bilateral corrugated, cobblestone changes of the buccal mucosa in a patient with Crohn disease. (Courtesy Dr. John Lovas.)■ Figure 17.28 Crohn Disease Erythematous gingival enlargement with aphthous-like ulceration involving the mandibular anterior labial vestibule in a 20-year-old female. Multiple biopsies of her gastrointestinal tract identified nonnecrotizing granulomatous inflammation in two sites only: the gingivae and the terminal ileum. 524 17 Oral Manifestations of Systemic Disease Pyostomatitis VegetansFigs. 17.29 and 17.30Pyostomatitis vegetans is an uncommon manifestation of inammatory bowel disease, with most cases being associated with ulcerative colitis. Some patients with Crohn disease may also present with pyostomatitis vegetans. A similar skin condition, known as pyodermatitis vegetans, may develop simultaneously in some instances.Pyostomatitis vegetans appears as yellow-white, slightly elevated, circinate mucosal lesions that can aect most oral mucosal sites, although the buccal mucosa, labial mucosa, gingivae, and palate seem to be favored. e lesions are oen described as having a “snail-track” appearance clinically. For some patients the lesions are relatively asymptomatic, but others may complain of pain or tenderness.e diagnosis is sometimes made on the basis of the characteristic clinical appearance of the lesions. Biopsy will show a unique pattern of microabscesses that are primarily composed of eosinophils in the spinous layer of the surface epithelium. Varying degrees of intraepithelial edema may be present, simulating an intraepithelial cle.Usually pyostomatitis vegetans will resolve when the inammatory bowel disease is treated. Occasionally this process may develop prior to diagnosis of inammatory bowel disease, in which case the lesions will respond to application of one of the stronger topical corticosteroid gel preparations.Uremic StomatitisFig. 17.31Uremic stomatitis is a rare condition that develops in patients with end-stage renal disease. Patients who are not receiving adequate hemodialysis will typically have markedly elevated levels of urea in their blood. is is thought to be secreted in the saliva of aected patients. e lesions are thought to be caused by the action of urease, produced by some of the oral microora, on the urea in the saliva, liberating ammonia and causing chemical injury to the oral mucosa.Patients with uremic stomatitis complain of diuse oral mucosal pain and loss of taste or development of dysgeusia. Loosely adherent white plaques are found primarily on the tongue and buccal mucosa. Microscopic descriptions of this process are uncommon, but most describe a peculiar hyperparakeratosis with acanthosis and minimal inammation.Treatment consists of renal dialysis, which corrects the blood urea levels and eliminates the urea substrate from the saliva. e oral lesions typically resolve in a few days. 17 Oral Manifestations of Systemic Disease 525■ Figure 17.29 Pyostomatitis Vegetans Superficial pustules, some of which suggest a “snail-track” pattern. ■ Figure 17.30 Pyostomatitis Vegetans Same patient as in Fig. 17.29 5 days after systemic corticosteroid therapy. AB■ Figure 17.31 Uremic Stomatitis (A) White plaques of the ventral tongue in a patient suffering from chronic renal failure. (B) Same patient, showing resolution of the white plaques following renal dialysis. (Courtesy Dr. William Ross.) 526 17 Oral Manifestations of Systemic Disease 526 17 Oral Manifestations of Systemic Disease BibliographyJaundiceCarroll WJ, Peck T, Jenkins TL. Periocular, periorbital, and orbital pathology in liver disease. Surv Ophthalmol. 2017;62:e134–e149.Fargo MV, Grogan SP, Saguil A. Evaluation of jaundice in adults. Am Fam Physician. 2017;95:164–168.Pratt DS, Kaplan MM. Jaundice. In: Longo DL, Fauci AS, Kasper DL, et al, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012:324–329.Winger J, Michelfelder A. Diagnostic approach to the patient with jaundice. Prim Care. 2011;38:469–482.Lipoid ProteinosisCallizo M, Ibáñez-Flores N, Laue J, et al. Eyelid lesions in lipoid proteinosis or Urbach-Wiethe disease: case report and review of the literature. Orbit. 2011;30:242–244.Kartal D, Çınar SL, Kartal L, et al. Lipoid proteinosis. Acta Dermatovenerol APA. 2016;25:19–21.Molina-Ruiz AM, Cerroni L, Kutzner H, et al. Cutaneous deposits. Am J Dermatopathol. 2014;36:1–48.Ranjan R, Goel K, Sarkar R, et al. Lipoid proteinosis: a case report in two siblings. Dermatol Online J. 2015;21:20.AmyloidosisAnkarcrona M, Winblad B, Monteiro C, et al. Current and future treatment of amyloid diseases. J Intern Med. 2016;280:177–202.Gertz M. CME information: immunoglobulin light chain amyloidosis: 2016 update on diagnosis, prognosis, and treatment. Am J Hematol. 2016;91:947–956.Mangold AR, Torgerson RR, Rogers III RS. Diseases of the tongue. Clin Dermatol. 2016;34:458–469.Pau M, Reinbacher KE, Feichtinger M, et al. Surgical treatment of macroglossia caused by systemic primary amyloidosis. Int J Oral Maxillofac Surg. 2013;42:294–297.Suzuki T, Kusumoto S, Yamashita T, et al. Labial salivary gland biopsy for diagnosing immunoglobulin light chain amyloidosis: a retrospective analysis. Ann Hematol. 2016;95:279–285.Wechalekar AD, Gillmore JD, Hawkins PN. Systemic amyloidosis. Lancet. 2016;387:2641–2654.XanthelasmaDey A, Aggarwal R, Dwivedi S, et al. Cardiovascular prole of xanthelasma palpebrarum. Biomed Res Int. 2013;3. Article ID 932863.Frew JW, Murrell DF, Haber RM. Fiy shades of yellow: a review of the xanthodermatoses. Int J Dermatol. 2015;54:1109–1123.Heng JK, Chua SH, Goh CL, et al. Treatment of xanthelasma palpebrarum with a 1064-nm, Q-switched Nd:YAG laser. J Am Acad Dermatol. 2017;77:728–734.Kavoussi H, Ebrahimi A, Rezaei M, et al. Serum lipid prole and clinical characteristics of patients with xanthelasma palpebrarum. An Bras Dermatol. 2016;91:468–471.Sayin I, Ayli M, Oğuz AK, et al. Xanthelasma palpebrarum: a new side eect of nilotinib. BMJ Case Rep. 2016;doi:10.1136/bcr-2015-213511.ScurvyGolriz F, Donnelly LF, Devaraj S, et al. Modern American scurvy—experience with vitamin C deciency at a large children’s hospital. Pediatr Radiol. 2017;47:214–220.Hafez D, Saint S, Griauzde J, et al. A decient diagnosis. N Engl J Med. 2016;374:1369–1374.Harrison LB, Nash MJ, Fitzmaurice D, et al. Investigating easy bruising in an adult. BMJ. 2017;356:j251. doi:10.1136/bmj.j251. Published 9 February 2017.Kletzel M, Powers K, Hayes M. Scurvy: a new problem for patients with chronic GVHD involving mucous membranes; an easy problem to resolve. Pediatr Transplant. 2014;18:524–526.Ma NS, ompson C, Weston S. Brief report: scurvy as a manifestation of food selectivity in children with autism. J Autism Dev Disord. 2016;46:1464–1470.Singh S, Richards SJ, Lykins M, et al. An underdiagnosed ailment: scurvy in a tertiary care academic center. Am J Med Sci. 2015;349:372–373.Iron-Deficiency AnemiaBetesh AL, Santa Ana CA, Cole JA, et al. Is achlorhydria a cause of iron deciency anemia? Am J Clin Nutr. 2015;102:9–19.Cascio MJ, DeLoughery TG. Anemia: evaluation and diagnostic tests. Med Clin N Am. 2017;101:263–284.DeLoughery TG. Iron deciency anemia. Med Clin N Am. 2017;101:319–332.Lu S-Y. Perception of iron deciency from oral mucosa alterations that show a high prevalence of Candida infection. J Formosan Med Assoc. 2016;115:e619–e627.Powell DJ, Achebe MO. Anemia for the primary care physician. Prim Care Clin Oce Pract. 2016;43:527–542.Wu Y-C, Wang Y-P, Chang JY-F, et al. Oral manifestations and blood prole in patients with iron deciency anemia. J Formosan Med Assoc. 2014;113:e83–e87.PellagraCrook MA. e importance of recognizing pellagra (niacin deciency) as it still occurs. Nutrition. 2014;30:729–730.Gupta Y, Shah I. Ethionamide-induced pellagra. J Tropical Pediatr. 2015;61:301–303.Kitamura S, Hata H, Shimizu H. Dark-violaceous lesions on the dorsa of both hands. Clin Exp Dermatol. 2015;40:941–942.Mooney SJ, Knox J, Morabia A. e ompson-McFadden Commission and Joseph Goldberger: contrasting 2 historical investigations of pellagra in cotton mill villages in South Carolina. Am J Epidemiol. 2014; 180:235–244.Terada N, Kinoshita K, Taguchi S, et al. Wernicke encephalopathy and pellagra in an alcoholic and malnourished patient. BMJ Case Rep. 2015;doi:10.1136/bcr-2015-209412.Pernicious AnemiaBizzaro N, Antico A. Diagnosis and classication of pernicious anemia. Autoimmun Rev. 2014;13:565–568.Couderc A-L, Camalet J, Schneider S, et al. Cobalamin deciency in the elderly: aetiology and management: a study of 125 patients in a geriatric hospital. J Nutr Health Aging. 2015;19:234–239.Green R. Vitamin B12 deciency from the perspective of a practicing hematologist. Blood. 2017;129:2603–2611.Green R, Mitra AD. Megaloblastic anemias: nutritional and other causes. Med Clin N Am. 2017;101:297–317.Powell DJ, Achebe MO. Anemia for the primary care physician. Prim Care Clin Oce Pract. 2016;43:527–542.Shipton MJ, achil J. Vitamin B12 deciency – a 21st century perspective. Clin Med. 2015;15:145–150.RicketsDeLuca HF. Vitamin D: historical overview. Vitamins Hormones. 2016;100.Gittoes NJL. Vitamin D – what is normal according to latest research and how should we deal with it? Clin Med. 2016;16:171–174.Kalra S. Vitamin D deciency: pragmatic suggestions for prevention and treatment. J Pak Med Assoc. 2017;67:1116–1118.Prentice A. Nutritional rickets around the world. J Steroid Biochem Mol Biol. 2013;136:201–206.Reid IR. What diseases are causally linked to vitamin D deciency? Arch Dis Child. 2016;101:185–189.Vitamin D-Resistant RicketsBiosse-Duplan M, Coyac BR, Bardet C, et al. Phosphate and vitamin D prevent periodontitis in X-Linked hypophosphatemia. J Dent Res. 2017;96:388–395.Capelli S, Donghi V, Maruca K, et al. Clinical and molecular heterogeneity in a large series of patients with hypophosphatemic rickets. Bone. 2015;79:143–149. 17 Oral Manifestations of Systemic Disease 527 17 Oral Manifestations of Systemic Disease 527Che H, Roux C, Etcheto A, et al. Impaired quality of life in adults with X-linked hypophosphatemia and skeletal symptoms. Eur J Endocrinol. 2016;174:325–333.Li S-S, Gu J-M, Yu W-J, et al. Seven novel and six de novo PHEX gene mutations in patients with hypophosphatemic rickets. Int J Mol Med. 2016;38:1703–1714.Sabandal MMI, Robotta P, Bürklein S, et al. Review of the dental implications of X-linked hypophosphataemic rickets (XLHR). Clin Oral Invest. 2015;19:759–768.Souza AP, Kobayashi TY, Lourenço-Neto N, et al. Dental manifestation of patient with vitamin D-resistant rickets. J Appl Oral Sci. 2013;21: 601–606.HypophosphatasiaFoster BL, Ramnitz MS, Gafni RI, et al. Rare bone diseases and their dental, oral, and craniofacial manifestations. Crit Rev Oral Biol Med. 2014;93:7S–19S.Hollis A, Arundel P, High A, et al. Current concepts in hypophosphatasia: case report and literature review. Int J Paediatr Dent. 2013;23: 153–159.Whyte MP. Hypophosphatasia: enzyme replacement therapy brings new opportunities and new challenges. J Bone Mineral Res. 2017;32: 667–675.Whyte MP. Hypophosphatasia: an overview for 2017. Bone. 2017;102: 15–25.HyperparathyroidismDuan K, Gomez-Hernandez K, Mete O. Clinicopathological correlates of hyperparathyroidism. J Clin Pathol. 2015;68:771–787.Dulfer RR, Franssen GJH, Hesselink DA, et al. Systematic review of surgical and medical treatment for tertiary hyperparathyroidism. Br J Surg. 2017;104:804–813.Guarnieri V, Seaberg RM, Kelly C, et al. Large intragenic deletion of CDC73 (exons 4-10) in a three-generation hyperparathyroidism-jaw tumor (HPT-JT) syndrome family. BMC Med Genet. 2017;18:83.Mathews JW, Winchester R, Alsaygh N, et al. Hyperparathyroidism-jaw tumor syndrome: an overlooked cause of severe hypercalcemia. Am J Med Sci. 2016;352:302–305.Rodríguez-Portillo M, Rodríguez-Ortiz ME. Secondary hyperparathyroidism: pathogenesis, diagnosis, preventive and therapeutic strategies. Rev Endocr Metab Disord. 2017;18:79–95.Salam SN, Khwaja A, Wilkie ME. Pharmacological management of secondary hyperparathyroidism in patients with chronic kidney disease. Drugs. 2016;76:841–852.Stephen AE, Mannstadt M, Hodin RA. Indications for surgical management of Hyperparathyroidism. A review. JAMA Surg. 2017;152: 878–882.Wilhelm SM, Wang TS, Ruan DT, et al. e American Association of Endocrine Surgeons guidelines for denitive management of primary hyperparathyroidism. JAMA Surg. 2016;151:959–968.Yang Q, Sun P, Li J, et al. Skeletal lesions in primary hyperparathyroidism. Am J Med Sci. 2015;349:321–327.Yuen NK, Ananthakrishnan S, Campbell MJ. Hyperparathyroidism of renal disease. Perm J. 2016;20:79–83.Renal OsteodystrophyBaracaldo RM, Bao D, Iampornpipopchai P, et al. Facial disgurement due to osteitis brosa cystica or brown tumor from secondary hyperparathyroidism in patients on dialysis: a systematic review and an illustrative case report. Hemodialysis Int. 2015;19:583–592.Guimarães-Henriques JC, de Melo Castilho JC, Jacobs R, et al. Severe secondary hyperparathyroidism and panoramic radiography parameters. Clin Oral Invest. 2014;18:941–948.Kemper MJ, van Husen M. Renal osteodystrophy in children: pathogenesis, diagnosis and treatment. Pediatrics. 2014;26:180–186.Lundquist AL, Nigwekar SU. Optimal management of bone mineral disorders in chronic kidney disease and ESRD. Curr Opin Nephrol Hypertens. 2016;25:120–126.Raubenheimer EJ, Noe CE, Hendrik HD. Recent developments in metabolic bone diseases: a gnathic perspective. Head Neck Pathol. 2014;8:475–481.Raubenheimer EJ, Noe CE, Mohamed A. Expansive jaw lesions in chronic kidney disease: review of the literature and a report of two cases. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015;119:340–345.Rodríguez-Portillo M, Rodríguez-Ortiz ME. Secondary hyperparthyroidism: pathogenesis, diagnosis, preventive and therapeutic strategies. Rev Endocr Metab Disord. 2017;18:79–95.Addison DiseaseBain A, Stewart M, Mwamure P, et al. Addison’s disease in a patient with hypothyroidism: autoimmune polyglandular syndrome type 2, Bain A, et al. BMJ Case Rep. 2015;doi:10.1136/bcr-2015-210506.Bensing S, Hulting A-L, Husebye ES, et al. Epidemiology, quality of life and complications of primary adrenal insuciency: a review. Eur J Endocrinol. 2016;175:R107–R116.Burton C, Cottrell E, Edwards J. Addison’s disease: identication and management in primary care. Br J Gen Practice. 2015;65:488–490.Charmandari E, Nicolaides NC, Chrousos GP. Adrenal insuciency. Lancet. 2014;383:2152–2167.Gondak R-O, da Silva-Jorge R, Jorge J, et al. Oral pigmented lesions: clinicopathologic features and review of the literature. Med Oral Patol Oral Cir Bucal. 2012;17:e919–e924.Michels A, Michels N. Addison disease: early detection and treatment principles. Am Fam Physician. 2014;89:563–568.Diabetes MellitusFierabracci A. Type 1 Diabetes in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED): a “rare” manifestation in a “rare” disease. Int J Mol Sci. 2016;17:1106.Gilbert MP. Screening and treatment by the primary care provider of common diabetes complications. Med Clin N Am. 2015;99:201–219.González-Serrano J, Serrano J, López-Pintor RM, et al. Prevalence of oral mucosal disorders in diabetes mellitus patients compared with a control group. J Diabetes Res. 2016;2016:11. Article ID 5048967.López-Pintor RM, Casañas E, González-Serrano J, et al. Xerostomia, hyposalivation, and salivary ow in diabetes patients. J Diabetes Res. 2016;2016:15. Article ID 4372852.Meah F, Juneja R. Insulin tactics in type 2 diabetes. Med Clin N Am. 2015;99:157–186.Preshaw PM, Bissett SM. Periodontitis oral complication of diabetes. Endocrinol Metab Clin N Am. 2013;42:849–867.Stephens E. Insulin therapy in type 1 diabetes. Med Clin N Am. 2015;99:145–156.omas CC, Philipson LH. Update on diabetes classication. Med Clin N Am. 2015;99:1–16.Crohn DiseaseAlawi F. An update on granulomatous diseases of the oral tissues. Dent Clin North Am. 2013;57:657–671.Feuerstein JD, Cheifetz AS. Crohn disease: epidemiology, diagnosis, and management. Mayo Clin Proc. 2017;92:1088–1103.Laass MW, Roggenbuck D, Conrad K. Diagnosis and classication of Crohn’s disease. Autoimmun Rev. 2014;13:467–471.Laranjeira N, Fonseca J, Meira T, et al. Oral mucosa lesions and oral symptoms in inammatory bowel disease patients. Arq Gastroenterol. 2015;52:105–110.Muhvić-Urek M, Tomac-Stojmenović M. Mijandrušić-Sinčić B: Oral pathology in inammatory bowel disease. World J Gastroenterol. 2016;22:5655–5667.Pereira MS, Munerato MC. Oral manifestations of inammatory bowel diseases: two case reports. Clin Med Res. 2016;14:46–52.Pyostomatitis VegetansClark LG, Tolkachjov SN, Bridges AG, et al. Pyostomatitis vegetans (PSV)-pyodermatitis vegetans (PDV): a clinicopathologic study of 7 cases at a tertiary referral center. J Am Acad Dermatol. 2016;75: 578–584.Magliocca KR, Fitzpatrick SG. Autoimmune disease manifestations in the oral cavity. Surg Pathol. 2017;10:57–88. 528 17 Oral Manifestations of Systemic Disease 528 17 Oral Manifestations of Systemic Disease rash B, Patel M, Shah KR, et al. Cutaneous manifestations of gastrointestinal disease - part II. J Am Acad Dermatol. 2013;68: 211.e1–211.e33.Wu YH, Chang JYF, Chen H-M, et al. Pyostomatitis vegetans: an oral manifestation of inammatory bowel disease. J Formosan Med Assoc. 2015;114:672–e673.Uremic StomatitisLeão JC, Gueiros LAM, Segundo AVL, et al. Uremic stomatitis in chronic renal failure. Clinics. 2005;60:259–262.Liao C-Y. Uremic stomatitis. Quarterly J Med. 2017;110:247–248.Proctor R, Kumar N, Stein A, et al. Oral and dental aspects of chronic renal failure. J Dent Res. 2005;84:199–208. 529529IndexAAbfraction, 48, 49fAbrasion, 46, 47fAbscesspalatal, 80, 81fperiodontal, 102, 103fAcanthosis nigricans, 498, 499fAcinic cell carcinoma, 286, 287fAcquired immunodeciency syndrome (AIDS), 154related Kaposi sarcoma, 158, 158f–159fAcquired melanocytic nevus, 236Acral keratoses, in multiple hamartoma syndrome, 472Actinic cheilitis, 252, 253fActinic cheilosis, 252, 253fActinic keratosis, 252, 253fActinic lentigines, 234, 235fActinomyces israelii, 118Actinomycosis, 118, 119fActive tuberculosis, 114Acute atrophic candidiasis, 128Acute herpetic gingivostomatitis, 142, 142f–143fAcute necrotizing ulcerative gingivitis. see Necrotizing ulcerative gingivitisAcute osteomyelitis, 88, 89fAcute retroviral syndrome, 162Acute tonsillitis, 110Addison disease, 520, 521fAddisonian crisis, 520Adenoameloblastoma, 440Adenoid cystic carcinoma, 290, 290f–291fAdenomacanalicular, 286, 287fpleomorphic, 284, 284f–285fcarcinoma ex, 292, 293fAdenomatoid odontogenic tumor (AOT), 440, 440f–441fAdenomatous polyposis coli (APC) tumor suppressor gene, 392Adrenal gland, pheochromocytomas of, 322African cutaneous Kaposi sarcoma, 340African lymphadenopathic Kaposi sarcoma, 340Age spots, 234, 235fAggregatibacter actinomycetemcomitans, 104Aggressive bromatosis, 308, 309f, 394Aggressive periodontitis, 104, 105fAIDS. see Acquired immunodeciency syndromeAL amyloidosis, 508Allergic contact stomatitis, to toothpaste, 210, 211fAllergic fungal sinusitis, 136Allergies, 205–222Alveolar rhabdomyosarcoma, 336Alveolar ridge keratosis, 238, 239fAmalgam, oral lichenoid reactions to, 212, 213fAmalgam tattoo, 190, 191fAmeloblastic carcinoma, 438, 439fAmeloblastic carcinosarcoma, 444Ameloblastic broma, 444, 445fAmeloblastic bro-odontoma (AFO), 446, 447fAmeloblastic brosarcoma, 444, 445fAmeloblastoma, 430–431, 432f–435fextraosseous, 436peripheral, 436, 437funicystic, 436, 437fAmelogenesis imperfecta, 70generalized pitted hypoplastic variant, 70fgeneralized thin hypoplastic variant, 71fhypocalcication variant, 71fsnow-capped hypomaturation variant, 71fAmputation neuroma, 318, 319fAmyloidosis, 508, 509fAneurysmal bone cyst, 380, 381fAngina, Ludwig, 88, 89fAngioedema, 216, 217fAngiobromas, in tuberous sclerosis, 470, 471fAngiosarcoma, 338, 339fAngular cheilitis, 130, 131fAnkyloglossia, 8, 9fanterior, 8posterior, 8Ankylosis, 54, 55fAnodontia, 54“Antibiotic sore mouth”, 128Antineoplastic therapy, dental disturbances due to, 44, 45fAntral pseudocyst, 194, 195fAphthous stomatitisherpetiform, 208, 209fHIV-associated, 162, 163fmajor, 206, 207fminor, 206, 207frecurrent, 206Apical periodontal cyst, 86, 87fArteriovenous malformations, 328Artery, caliber-persistent, 14, 15fAsh leaf spots, in tuberous sclerosis, 470Aspergilloma, 136Aspergillosis, 136, 137fAspergillus avus, 136Aspergillus fumigatus, 136Aspirin burn, 176, 177fAsymptomatic tonsilloliths, 110Attrition, 46, 47fAtypical gingivostomatitis. see Plasma cell gingivitisAutosomal dominant adult osteopetrosis, 368Autosomal recessive infantile osteopetrosis, 368Autosomal recessive intermediate osteopetrosis, 368BBacterial infections, 109–123actinomycosis, 118, 119fcat-scratch disease, 118–120, 119fcongenital syphilis, 118impetigo, 112, 113fleprosy (Hansen disease), 114, 115fnoma, 114–116, 115fsinusitis, 120, 121fsyphilis, 116tonsillitis, 110, 111ftonsilloliths, 110, 111ftuberculosis, 112–114, 113fBacterial sialadenitis, 280Bartonella henselae, 118–120Basal cell carcinoma, 264, 265fBatson paravertebral plexus, of veins, 406Batson plexus, 342Beau’s lines, 152Behçet syndrome, 208, 209fBence Jones protein, 362Benign intraepithelial dyskeratosis, hereditary, 462, 463fBenign lymphoepithelial lesion, 162, 282Benign migratory glossitis, 484, 484f–485fBenign mixed tumor, 284, 284f–285fBid condyle, 16, 17fBid uvula, 2, 3fBilirubin, 506Biliverdin, 506Bismuth staining, 13fBlastomyces dermatitidis, 132Blastomycosis, 132, 133fBlue nevus, 236, 237fBohn nodules, 26Bone marrow defect, focal osteoporotic, 370, 371fBone pathology, 367–410aneurysmal bone cyst, 380, 381fcementoblastoma, 396, 397fcemento-osseous dysplasia, 384central giant cell granuloma, 376, 376f–377fcentral ossifying broma, 388, 388f–389fcherubism, 378, 379fchondrosarcoma, 402, 403fcleidocranial dysplasia, 370, 371fdesmoplastic broma, 394, 395fEwing sarcoma, 402, 403fbrous dysplasia, 382, 382f–383forid cemento-osseous dysplasia, 386, 386f–387ffocal cemento-osseous dysplasia, 384, 385ffocal osteoporotic bone marrow defect, 370, 371fGardner syndrome, 392, 393fidiopathic osteosclerosis, 372, 372f–373fjuvenile ossifying broma, 390, 391fmassive osteolysis, 374, 375fmesenchymal chondrosarcoma, 404, 405fmetastatic tumors to the jaws, 406, 406f–407fosteoblastoma, 394, 395fosteoma, 390, 391fosteopetrosis, 368, 369fosteosarcoma, 398, 399f–401fPaget disease of bone, 374–376, 375fperiapical cemento-osseous dysplasia, 384, 385fsimple bone cyst, 380, 381fBone sequestration, oral ulceration with, 182, 183fBotryoid odontogenic cyst, 422, 423fBranchial cle cyst, 30, 31fBuccal bifurcation cyst, 66, 414, 415fBullous impetigo, 112Burnschemical, 176, 177felectrical, 174, 175fthermal, 174, 175fCCafé au lait spots, 320Calcifying cystic odontogenic tumor, 426, 426f–427fCalcifying epithelial odontogenic tumor (CEOT), 442, 443fCalcifying odontogenic cyst, 426, 426f–427fCaliber-persistent artery, 14, 15fCanalicular adenoma, 286, 287fCandida, in inammatory papillary hyperplasia, 306Candida albicans, 126“Candidal leukoplakia.” see Chronic hyperplastic candidiasisCandidiasischronic hyperplastic, 130, 131ferythematous, 128, 129fhuman immunodeciency virus-associated, 154, 154f–155fpseudomembranous, 126, 126f–127fPage numbers followed by “f ” indicate gures.Amelogenesis imperfecta (Continued) 530 Index Capillary malformations, 328Carcinomaacinic cell, 286, 287fadenoid cystic, 290, 290f–291fameloblastic, 438, 439fbasal cell, 264, 265fclear cell odontogenic, 438, 439fex pleomorphic adenoma, 292, 293fintraosseous mucoepidermoid, 288, 289fof maxillary sinus, 262–264, 263fmucoepidermoid, 288, 289fin odontogenic cysts, 428, 429fsarcomatoid, 262, 263fsecretory, 294, 295fspindle cell, 262, 263fsquamous cell, oral and oropharyngeal, 251f, 254–255, 256f–261fverrucous, 262, 263fCarcinosarcoma, 262, 263fCarotid artery syndrome, 22, 23fCathepsin C (CTSC) gene, 104Cat-scratch disease, 118–120, 119fCementoblastoma, 396, 397fCemento-osseous dysplasia, 384orid, 386, 386f–387ffocal, 384, 385fperiapical, 384, 385fCentral giant cell granuloma, 376, 376f–377fCentral giant cell “reparative” granuloma, 376Central odontogenic broma, 450, 451fCentral ossifying broma, 388, 388f–389fCentral papillary atrophy. see Median rhomboid glossitisCervical enamel extension, 66, 67fCervical lymphoepithelial cyst, 30, 31fChancre, 116, 117fCharm needles, 192, 193fCheilitisactinic, 252, 253fangular, 130, 131fexfoliative, 184, 185fMiescher, 214Cheilitis glandularis, 280, 281fCheilitis granulomatosa, 214Cheilosis, actinic, 252, 253fChemical burns, 176, 177fChemical injuries, physical and, 169–203Chemotherapy-induced oral mucositis, 176–178, 177fCherubism, 378, 379fChickenpox, 148, 149fCholecalciferol, 514Chondrosarcoma, 402, 403fmesenchymal, 404, 405fChronic atrophic candidiasis. see Denture stomatitisChronic cutaneous lupus erythematosus (CCLE), 492Chronic hyperplastic candidiasis, 130, 131fChronic intraoral herpes, 146, 147fChronic lip ssure, 184, 185fChronic mucosal drug reactions, 218, 218f–219fChronic osteomyelitis, 88–90, 89fChronic pericoronitis, 102–104Chronic tonsillitis, 110Chronic ulcerative stomatitis, 490, 491fCicatricial (scarring) pemphigoid, 480, 480f–481fCinnamic aldehyde, contact stomatitis to, 220, 220f–221fClassic Kaposi sarcoma, 340Clear cell odontogenic carcinoma, 438, 439fCle lip and palate, 2, 3fin Van der Woude syndrome, 5fCle uvula, 2, 3fCleidocranial dysplasia, 370, 371fCoated tongue, 12Cobalamin, 512Cobalamin-intrinsic factor complex, 512Coccidioides immitis, 134Coccidioides posadasii, 134Coccidioidomycosis, 134, 135f“Cold sore.” see Herpes labialisCommissural lip pits, 4, 5f“Common mole.” see Acquired melanocytic nevusCommon wart, 224, 225fComplex odontoma, 446, 447fConcrescence, 60, 61fCondensing osteitis, 90, 91fCondylar hyperplasia, 16, 17fCondyle, bid, 16, 17fCondyloma acuminatum, 226, 227fCondyloma lata, 116Congenital epulis, 326, 327fCongenital granular cell lesion, 326Congenital neutropenia, 354Congenital syphilis, 118, 119fCongo red dye, amyloidosis and, 508Contact stomatitisallergic, to toothpaste, 210, 211fto cinnamic aldehyde, 220, 220f–221fCoronoid hyperplasia, 16, 17fCosmetic llers, 188, 189fCosmetic tattooing, 192Cowden syndrome, 472, 473fCraniofacial brous dysplasia, 382CREST syndrome, 496, 497fCrohn disease, 522, 523fCrowe sign, 320Cunnilingus, ulcer from, 188, 189fCutaneous leishmaniasis, 136Cutaneous sinus, 82, 83fCutaneous xanthomata, 508Cyclic neutropenia, 354Cystaneurysmal bone, 380, 381fapical periodontal, 86, 87fbotryoid odontogenic, 422, 423fbranchial cle, 30, 31fbuccal bifurcation, 66, 414, 415fcalcifying odontogenic, 426, 426f–427fcervical lymphoepithelial, 30, 31fdentigerous, 412, 412f–413fdermoid, 30, 31fepidermoid, 28, 29fepithelial inclusion, 28, 29feruption, 414, 415ffollicular, 412, 412f–413fgingivalof adult, 424, 425fof newborn, 424, 425fglandular odontogenic, 428, 429fGorlin, 426, 426f–427fincisive canal, 26, 27finammatory collateral, 414, 415finammatory dentigerous, 412, 413finfundibular, 28, 29flatent bone, 24, 24f–25flateral periodontal, 422, 423fnasopalatine duct, 26, 27foral lymphoepithelial, 32, 33forthokeratinized odontogenic, 422, 423fparadental, 414, 415fperiapical, 86, 87fpilar, 28, 29fradicular, 86, 87fresidual periapical, 86, 87fsalivary duct, 276, 277fsialo-odontogenic, 428, 429fsimple bone, 380, 381fstatic bone, 24, 24f–25fsurgical ciliated, 194, 195fthyroglossal duct, 30, 31fthyroglossal tract, 30, 31fCystic hygroma, 334, 335fCystic lymphoid hyperplasia, 162DDarier disease, 466, 467flocalized, 466, 467f. see also Warty dyskeratomaDehydroepiandrosterone (DHEA), 520Dementia, in pellagra, 510Dens evaginatus, 62, 63fDens invaginatus, 64, 65fDense bone island, 372, 372f–373fDental uorosis, 44, 45fDental granuloma, 84, 85fDentigerous cyst, 412, 412f–413fDentin dysplasia, type 1, 74, 75fDentin sialophosphoprotein (DSPP)-associated dentin disorders, 72, 73fDentinogenesis imperfecta, 72, 73fDentinogenic ghost cell tumor, 426, 426f–427fDenture epulis, 304, 304f–305fDenture stomatitis, 130, 131fDermatitis, in pellagra, 510Dermatologic diseases, 457–503acanthosis nigricans, 498, 499fchronic ulcerative stomatitis, 490, 491fCREST syndrome, 496, 497fDarier disease, 466, 467fdyskeratosis congenita, 464, 465fectodermal dysplasia, 458, 459fepidermolysis bullosa, 474, 475ferythema migrans, 484, 484f–485ferythema multiforme, 482, 482f–483fgra-versus-host disease, 490, 491fhereditary benign intraepithelial dyskeratosis, 462, 463fhereditary hemorrhagic telangiectasia, 468, 469fhereditary mucoepithelial dysplasia, 462, 463flichen planus, 486, 487f–489flupus erythematosus, 492, 492f–493fmucous membrane pemphigoid, 480, 480f–481fmultiple hamartoma syndrome, 472, 473fpachyonychia congenita, 460, 461fparaneoplastic pemphigus, 478, 478f–479fpemphigus, 476, 476f–477fPeutz-Jeghers syndrome, 468, 469fpsoriasis, 496, 497fsystemic sclerosis, 494, 494f–495ftuberous sclerosis, 470, 471fwarty dyskeratoma, 466, 467fwhite sponge nevus, 458, 459fxeroderma pigmentosum, 464, 465fDermatosis papulosa nigra, 230, 231fDermoid cyst, 30, 31fDesmoplastic ameloblastoma, 430–431, 434fDesmoplastic broma, 394, 395fDiabetes mellitus, 522, 523fDiascopy, 14Diuse cutaneous systemic sclerosis, 494Diuse gingivitis, 94Dilaceration, 68, 69fDiscolorations of teeth, 52Distodens, 56Distomolar, dened, 56Double lip, 2, 3fDouble teeth, 60, 60f–61fDrug reactions, chronic mucosal, 218, 218f–219fDrug-induced gingival overgrowth (drug-related gingival hyperplasia), 100, 101fDrug-induced pigmentation, 196, 197fDry mouth, 178DSPP-associated dentin disorders, 72, 73fDyskeratosiscongenita, 464, 465fhereditary benign intraepithelial, 462, 463fEEagle syndrome, 22, 23fEcchymosis, 186, 187fEctodermal dysplasia, 458, 459fElectrical burns, 174, 175fEmbryonal rhabdomyosarcoma, 336Enameldefects ofenvironmental, 42, 43fsyndrome-associated, 68, 69fhypoplasia, 42mottled, 44opacities, 42pearls, 64, 65fEnamelomas, 64, 65fEncephalotrigeminal angiomatosis, 332Endemic Kaposi sarcoma, 340Enostosis, 372, 372f–373fEosinophilic granuloma, 356Eosinophilic ulcer. see Traumatic granulomaEphelides, 234, 235fEpidermoid cyst, 28, 29fEpidermolysis bullosa, 474, 475facquisita, 474Epithelial inclusion cyst, 28, 29fEpithelial pathology, 223–271actinic cheilosis, 252, 253factinic keratosis, 252, 253factinic lentigines, 234, 235falveolar ridge keratosis, 238, 239fbasal cell carcinoma, 264, 265fblue nevus, 236, 237fcarcinoma of maxillary sinus, 262–264, 263fcondyloma acuminatum, 226, 227fdermatosis papulosa nigra, 230, 231fephelides, 234, 235ferythroplakia, 246, 247fDermatologic diseases (Continued) Index 531keratoacanthoma, 252–254, 253fLaugier-Hunziker syndrome, 232, 233fleukoplakia, 240, 241f–243fmelanoacanthoma, oral, 234, 235fmelanocytic nevus, 236, 237fmelanoma, 266, 267fmelanotic macule, oral, 232, 233fmolluscum contagiosum, 228, 229fmultifocal epithelial hyperplasia, 226, 227fnicotine stomatitis, 238, 239fproliferative verrucous leukoplakia, 244, 244f–245fsebaceous hyperplasia, 230–232, 231fseborrheic keratosis, 230, 231fsinonasal papillomas, 226–228, 227fspindle cell carcinoma, 262, 263fsquamous cell carcinoma, oral and oropharyngeal, 254–255, 256f–261fsquamous papilloma, 224, 225fsubmucous brosis, oral, 250, 251ftobacco pouch keratosis, 248, 249fverruca vulgaris, 224, 225fverruciform xanthoma, 228, 229fverrucous carcinoma, 262, 263fEpstein pearls, 26, 27fEpstein-Barr virus (EBV) infection, 148Epulisdened, 304ssuratum, 304, 304f–305fgranulomatosa, 312, 313fErosion, 48, 49fEruption cyst, 414, 415fEruption hematoma, 414, 415fErythema migrans, 484, 484f–485fErythema multiforme, 482, 482f–483fErythematous candidiasis, 128, 129fErythroleukoplakia, 246, 247fErythroplakia, 246, 247fEwing sarcoma, 402, 403fExfoliative cheilitis, 184, 185fExostoses, 18buccal, 18, 19fpalatal, 18, 19freactive subpontine, 18, 19fExternal resorption, 50, 51fExtraosseous ameloblastoma, 436FFactitial injury, 172Familial adenomatous polyposis (FAP), 392Familial hypophosphatemic rickets, 516Familial medullary thyroid carcinoma syndrome, 322“Fever blister.” see Herpes labialisFibroepithelial polyps, in multiple hamartoma syndrome, 472Fibroma, 300, 300f–301fFibromatosis, gingival, 98, 99fFibrous dysplasia, 382, 382f–383fFissured tongue, 10, 11fFlorid cemento-osseous dysplasia, 386, 386f–387fFluorosis, dental, 44, 45fFocal cemento-osseous dysplasia, 384, 385fFocal epithelial hyperplasia, 226, 227fFocal melanosis, oral, 232, 233fFocal mucinosis, oral, 302, 303fFocal osteoporotic bone marrow defect, 370, 371fFocal sclerosing osteitis. see Condensing osteitisFocal sclerosing osteomyelitis. see Condensing osteitisFollicular cyst, 412, 412f–413fFordyce granules, 6, 7fForeign body gingivitis, 98, 99fFournier molars, 118Freckle-like pigmentation, 320Freckles, 234, 235fFungal infections, 125–139angular cheilitis, 130, 131faspergillosis, 136, 137fblastomycosis, 132, 133fchronic hyperplastic candidiasis, 130, 131fcoccidioidomycosis, 134, 135fdenture stomatitis, 130, 131ferythematous candidiasis, 128, 129fhistoplasmosis, 132, 133fmedian rhomboid glossitis, 128, 129fmucormycosis, 134–136, 135fparacoccidioidomycosis, 134, 135fpseudomembranous candidiasis, 126, 126f–127fFungus ball, 136Fusion, 60, 61fGGardner syndrome, 392, 393f“Garré’s osteomyelitis.” see Proliferative periostitisGemination, 60, 60fGeneralized aggressive periodontitis, 104Geographic tongue, 484, 484f–485fGhost teeth, 74Giant cell broma, 302, 303fGingival cystof adult, 424, 425fof newborn, 424, 425fGingival bromatosis, 98, 99f, 308Gingivitis, 94, 95fforeign body, 98, 99flocalized juvenile spongiotic, 94, 95fnecrotizing ulcerative, 96, 97fplasma cell, 96, 97fstrawberry, 216Gingivostomatitis, herpetic, acute, 142, 142f–143fGlandular odontogenic cyst, 428, 429fGlossitismedian rhomboid, 128, 129fin pellagra, 510Gorham disease, 374, 375fGorham-Stout syndrome, 374, 375fGorlin cyst, 426, 426f–427fGorlin syndrome, 418, 419f–421fGra-versus-host disease, 490, 491fGranular cell myoblastoma, 324Granular cell tumor, 324, 325fGranules, Fordyce, 6, 7fGranulomacentral giant cell, 376, 376f–377fdental, 84, 85fgravidarum, 310periapical, 84, 85fperipheral giant cell, 314, 315fpyogenic, 310, 310f–311ftraumatic, 172, 173fGranulomatosisorofacial, 214, 214f–215fwith polyangiitis, 216, 217fGranulomatous angiitis, 150Gumma, 116, 117fHHairy leukoplakia, human immunodeciency virus-associated, 156, 157fHairy tongue, 12, 12f–13fHand-foot-and-mouth disease, 152, 153fHand-Schüller-Christian disease, 356Hansen disease, 114, 115fHeck disease, 226, 227fHemangioma, 328, 329fHemangioma of infancy, 328Hemangiopericytoma, 308Hematologic disorders, 349–365hemophilia, 352, 353fHodgkin lymphoma, 360, 361fLangerhans cell histiocytosis, 356, 357fleukemia, 356, 357flymphoid hyperplasia, 350, 350f–351fmultiple myeloma, 362, 363fmycosis fungoides, 360, 361fneutropenia, 354, 355fNK/T-cell lymphoma, nasal type, 360, 361fnon-Hodgkin lymphoma, 358, 359fplasmacytoma, 362, 363fplasminogen deciency, 354, 355fthalassemia, 352, 353fthrombocytopenia, 354–356, 355fHematoma, 186, 187fHemihyperplasia, 34, 34f–35fHemihypertrophy, 34Hemoglobin, 506Hemophilia, 352, 353fHemophilia A, 352Hemophilia B, 352, 353fHemorrhage, mucosal or submucosal, 186, 187fHemorrhagic telangiectasia, hereditary, 468, 469fHepatocytes, 506Hereditary benign intraepithelial dyskeratosis, 462, 463fHereditary hemorrhagic telangiectasia, 468, 469fHereditary mucoepithelial dysplasia, 462, 463fHerpangina, 152, 153fHerpes labialis, 144, 145fHerpes simplex virus (HSV) infection, 144Herpes simplex virus type 1 (HSV-1) infection, 146acute herpetic gingivostomatitis caused by, 142Herpes zoster, 150, 150f–151fHerpetic whitlow, 144, 145fHerpetiform aphthous stomatitis, 208, 209fHistoplasma capsulatum, 132, 162Histoplasmosis, 132, 133fHIV-associated, 162–164, 163fHIV. see Human immunodeciency virusHodgkin lymphoma, 360, 361fHuman herpesvirus 8 (HHV-8), 340Human immunodeciency virus (HIV), 154aphthous stomatitis, 162, 163fhistoplasmosis, 162–164, 163fand human papillomavirus-related lesions, 156, 157flymphadenopathy, 162, 163flymphoma, 164, 165foral candidiasis, 154, 154f–155foral hairy leukoplakia, 156, 157foral/head and neck squamous cell carcinoma, 164, 165fand periodontal disease, 160, 161fHuman papillomavirusoropharyngeal squamous cell carcinoma and, 258frelated lesions, human immunodeciency virus and, 156, 157fHutchinson incisors, 118, 119fHyalinosis cutis et mucosae, 506Hypercarotenemia, 506Hypercementosis, 66, 67fHyperdontia, 56, 57fHyperparathyroidism (HPT), 518, 518f–519fHyperparathyroidism-jaw tumor syndrome, 388Hyperplasiacondylar, 16, 17fcoronoid, 16, 17fdrug-related gingival, 100, 101finammatory brous, 304, 304f–305finammatory papillary, 306, 307flocalized juvenile spongiotic gingival, 94, 95flymphoid, 350, 350f–351fmultifocal/focal epithelial, 226, 227fsebaceous, 230–232, 231fsubpontic osseous, 18, 19fHyperplastic pulpitis, 80, 81fHypoadrenocorticism. see Addison diseaseHypodontia, 54, 55fHypophosphatasia, 516–518, 517fIIatrogenic Kaposi sarcoma, 340Iatrogenic trauma, in mucosal or submucosal hemorrhage, 186Idiopathic bone cavity. see Simple bone cystIdiopathic osteosclerosis, 372, 372f–373fImmune (“idiopathic”) thrombocytopenic purpura (ITP), 356Immunologic diseases, 205–222Impetigo, 112, 113fIncisive canal cyst, 26, 27fIncisorsHutchinson, 118, 119fshovel-shaped, 62, 63fInfectious mononucleosis, 148, 149fInammatory collateral cyst, 414, 415fInammatory dentigerous cyst, 412, 413fInammatory brous hyperplasia, 304, 304f–305fInammatory papillary hyperplasia, 306, 307fInfundibular cyst, 28, 29fIntentional tattoos, 192, 193fInternal resorption, 50, 51fIntrabony vascular malformation, 330, 331fIntraepithelial dyskeratosis, hereditary benign, 462, 463fIntraoral herpeschronic, 146, 147frecurrent, 146, 147fIntraosseous mucoepidermoid carcinoma, 288, 289fIron deciency anemia, 510, 511fIrritation broma, 300, 300f–301fJJae-Lichtenstein syndrome, 382, 383fJaundice, 506, 507fEpithelial pathology (Continued) 532 Index Jaws, metastatic tumors to, 406, 406f–407fJuvenile bromatosis. see Aggressive bromatosisJuvenile ossifying broma, 390, 391fJuvenile recurrent parotitis, 280Juvenile spongiotic gingival hyperplasia, localized, 94, 95fJuvenile spongiotic gingivitis, 94, 95fK“Kala-azar”, 136Kaposi sarcoma, 340, 341facquired immunodeciency syndrome-related, 158, 158f–159fKaposi sarcoma-associated herpesvirus (KSHV), 340Keratin 6a mutations, pachyonychia congenita and, 460Keratoacanthoma, 252–254, 253fKeratoconjunctivitis sicca, 282Keratocystic odontogenic tumor, 416, 416f–417fKeratosisactinic, 252, 253falveolar ridge, 238, 239fseborrheic, 230, 231ftobacco pouch, 248, 249fKeratosis follicularis, 466, 467fLLangerhans cell histiocytosis (LCH), 356, 357fLatent bone cyst, 24, 24f–25fLateral periodontal cyst, 422, 423fLaugier-Hunziker syndrome, 232, 233fLeaike denture broma, 306, 307fLeiomyoma, 326, 327fLeiomyosarcoma, 338, 339fLeishmaniasis, 136, 137fLeontiasis ossea, 374Leprosy, 114, 115fLetterer-Siwe disease, 356Leukemia, 356, 357fLeukoedema, 8, 9fLeukoplakia, 240, 241f–243fcandidal. see Chronic hyperplastic candidiasisin dyskeratosis congenita, 464hairy, human immunodeciency virus-associated, 156, 157foral squamous cell carcinoma in, 257fproliferative verrucous, 244, 244f–245fLichen planus, 486, 487f–489fLichenoid reactions, oral, to amalgam, 212, 213f“Ligneous conjunctivitis”, 354Limited cutaneous systemic sclerosis, 494Linea alba, 170, 171fLinear scleroderma, 32Lingual mandibular salivary gland depression, 24, 24f–25fLingual mandibular sequestration and ulceration. see Oral ulceration with bone sequestrationLingual thyroid, 10, 11fLip ssure, chronic, 184, 185fLipoid proteinosis, 506, 507fLipoma, 314, 315fLipscle, 2, 3fdouble, 2, 3fpits ofcommissural, 4, 5fparamedian, 4, 5fLisch nodules, 320“Liver clot”, 186Lobular capillary hemangioma, 310, 310f–311fLocalized aggressive periodontitis, 104Localized Darier disease, 466, 467f. see also Warty dyskeratomaLocalized juvenile spongiotic gingival hyperplasia, 94, 95fLocalized juvenile spongiotic gingivitis, 94, 95fLudwig angina, 88, 89fLupus erythematosus, 492, 492f–493fLymphadenopathy, HIV-associated, 162, 163fLymphangioma, 334, 335fLymphatic malformation, 334, 335fLymphoepithelial cyst, oral, 32, 33fLymphoid hyperplasia, 350, 350f–351fLymphomaHIV-associated, 164, 165fHodgkin, 360, 361fNK/T-cell, nasal type, 360, 361fnon-Hodgkin, 358, 359fMMacrocystic lymphatic malformations, 334Macrodontia, 58, 59fMacroglossia, 508Macule, oral melanotic, 232, 233fMajor aphthous stomatitis, 206, 207fMammary analogue secretory carcinoma (MASC), 294. see also Secretory carcinomaMarginal gingivitis, 94Massive osteolysis, 374, 375fMaxillary sinus, carcinoma of, 262–264, 263fMaxillofacial region, developmental defects of, 1–40McCune-Albright syndrome, 382Mechanical injury, 172Median rhomboid glossitis, 128, 129fMedication-related osteonecrosis of the jaws (MRONJ), 180, 181fMedullary thyroid carcinoma (MTC), 322Megaloblastic anemia, 512Melanoacanthoma, oral, 234, 235fMelanoacanthosis, 234, 235fMelanocytic nevus, 236, 237fMelanoma, 266, 267fMelanonychia, longitudinal, Laugier-Hunziker syndrome and, 232Melanotic macule, oral, 232, 233fMelanotic neuroectodermal tumor of infancy, 324, 325fMelkersson-Rosenthal syndrome, 214MEN1 gene, 322Mesenchymal chondrosarcoma, 404, 405fMesiodens, 56Metastatic adenocarcinoma, of lung, 406fMetastatic melanoma, 407fMetastatic thyroid carcinoma, 407fMetastatic tumorsto jaws, 406, 406f–407fof oral so tissues, 342, 343f“Meth mouth”, 182, 183fMethamphetamine, 182Microcystic lymphatic malformations, 334Microdontia, 58, 59fMiescher cheilitis, 214Minocycline-induced pigmentation, 196, 197fMinor aphthous stomatitis, 206, 207fMint candy pouch, 249fMixed lymphatic malformations, 334Molluscum contagiosum, 228, 229f“Mon o.” see Infectious mononucleosisMononucleosis, infectious, 148, 149fMonostotic brous dysplasia, 382Moon molars, 118Morsicatio, 170, 171fMorsicatio buccarum, 170, 171fMorsicatio labiorum, 170Morsicatio linguarum, 170, 171fMorsicatio mucosae oris. see MorsicatioMottled enamel, 44Mucocele, 274, 274f–275fMucocutaneous leishmaniasis, 136Mucoepidermoid carcinoma, 288, 289fintraosseous, 288, 289fMucoepithelial dysplasia, hereditary, 462, 463fMucormycosis, 134–136, 135fMucosal drug reactions, chronic, 218, 218f–219fMucosal hemorrhage, 186, 187fMucous membrane pemphigoid, 480, 480f–481fMucous patches, 116, 117fMucus extravasation phenomenon, 274, 274f–275fMuir-Torre syndrome, sebaceous hyperplasia and, 230Mulberry molars, 118Multifocal epithelial hyperplasia, 226, 227fMultiple endocrine neoplasia (MEN) syndromes, 322Multiple endocrine neoplasia type 2B, 322, 322f–323fMultiple hamartoma syndrome, 472, 473fMultiple myeloma, 362, 363fMunchausen syndrome, 172Mycetoma, 136Mycobacterium leprae, 114Mycobacterium tuberculosis, 112Mycosis fungoides, 360, 361fMyeloma, multiple, 362, 363fMyoepithelial sialadenitis, 282Myobroma, 308, 309fMyobromatosis, 308NNail dystrophy, in dyskeratosis congenita, 464Nasopalatine duct cyst, 26, 27fNatal teeth, 58, 59fNatural killer/T-cell lymphoma, nasal type, 360, 361fNecrotizing sialometaplasia, 282, 283fNecrotizing stomatitis, 160Necrotizing ulcerative gingivitis, 96, 97f, 160Necrotizing ulcerative periodontitis, 160Neonatal teeth, 58Neurilemoma, 316, 317fNeurobroma, 318, 319fNeurobromatosis, 318, 320type I, 320, 320f–321ftype II, 316Neurobromin, 320Neutropenia, 354, 355fNevoid basal cell carcinoma syndrome, 418, 419f–421fNevusblue, 236, 237fmelanocytic, 236, 237fwhite sponge, 458, 459fNiacin, 510Nicotinamide, 510Nicotinamide adenine dinucleotide (NAD+), 510Nicotinamide adenine dinucleotide phosphate (NADP+), 510Nicotine stomatitis, 238, 239fNicotinic acid, 510Noma, 114–116, 115fNon-Hodgkin lymphomas, 358, 359fOOcular dryness, 282Odontodysplasia, regional, 74, 75fOdontogenic cysts and tumors, 411–456adenomatoid odontogenic tumor, 440, 440f–441fameloblastic carcinoma, 438, 439fameloblastic broma, 444, 445fameloblastic bro-odontoma, 446, 447fameloblastic brosarcoma, 444, 445fameloblastoma, 430–431, 432f–435fbuccal bifurcation cyst, 414, 415fcalcifying epithelial, 442, 443fcalcifying odontogenic cyst, 426, 426f–427fcarcinoma, 428, 429fcentral odontogenic broma, 450, 451fclear cell odontogenic carcinoma, 438, 439fcomplex odontoma, 446, 447fcompound odontoma, 448, 448f–449fdentigerous cyst, 412, 412f–413feruption cyst, 414, 415fgingival cystof adult, 424, 425fof newborn, 424, 425fglandular odontogenic cyst, 428, 429flateral periodontal cyst, 422, 423fnevoid basal cell carcinoma syndrome, 418, 419f–421fodontogenic keratocyst, 416, 416f–417fodontogenic myxoma, 452, 453forthokeratinized, 422, 423fperipheral ameloblastoma, 436, 437fperipheral odontogenic broma, 450, 451fsquamous odontogenic tumor, 442, 443funicystic ameloblastoma, 436, 437fOdontogenic keratocyst, 416, 416f–417fOdontogenic myxoma, 452, 453fOdontohypophosphatasia, 516Oligodontia, 54, 55fOpioid-induced palatal perforation, 182–184, 183fOral mucositischemotherapy-induced, 176–178, 177fradiation-induced, 178, 179fOral region, developmental defects of, 1–40Oral ulceration with bone sequestration, 182, 183fOral/head and neck squamous cell carcinoma, human immunodeciency virus and, 164, 165fOrofacial cleing, 2Orofacial granulomatosis, 214, 214f–215fOrthokeratinized odontogenic cyst, 422, 423fOsler-Weber-Rendu syndrome, 468, 469fOsseous choristoma, 328, 329fOsseous dysplasia. see Cemento-osseous dysplasiaOsteitis, condensing, 90, 91fOsteitis deformans, 374–376, 375fOsteoblastoma, 394, 395fOsteoma, 390, 391f Index 533Osteomyelitisacute, 88, 89fchronic, 88–90, 89ffocal sclerosing. see Condensing osteitisGarré’s. see Proliferative periostitissclerosing, 90, 91fOsteonecrosis of the jaws, medication-related, 180, 181fOsteopetrosis, 368, 369fOsteoporotic bone marrow defect, focal, 370, 371fOsteoradionecrosis, 178–180, 179fOsteosarcoma, 398, 399f–401fPPachyonychia congenita, 460, 461fPaget disease of bone, 374–376, 375fPalatal abscess, 80, 81fPalatal perforation, opioid-induced, 182–184, 183fPalate, cle, 2, 3fin Van der Woude syndrome, 5fPalisaded encapsulated neuroma, 318, 319fPapillary cystadenoma lymphomatosum, 286, 287fPapillary gingivitis, 94Papillomassinonasal, 226–228, 227fsquamous, 224, 225fPapillon-Lefèvre syndrome, 104, 105fParacoccidioides brasiliensis, 134Paracoccidioides lutzii, 134Paracoccidioidomycosis, 134, 135fParadental cyst, 414, 415fParamedian lip pits, 4, 5fParamolar, dened, 56Paraneoplastic pemphigus, 478, 478f–479fParotitis, juvenile recurrent, 280Parry-Romberg syndrome, 32, 33fParulis, 82, 83fPellagra, 510, 511fPemphigoid, mucous membrane, 480, 480f–481fPemphigus, 476, 476f–477fPeriadenitis mucosa necrotica recurrens (PMNR), 206, 207fPeriapical cemental dysplasia. see Periapical cemento-osseous dysplasiaPeriapical cemento-osseous dysplasia, 384, 385fPeriapical cyst, 86, 87fresidual, 86, 87fPeriapical disease, 79–92Periapical granuloma, 84, 85fPeriapical scar, 84, 85fPericoronitis, 102–104, 103fPeriodontal abscess, 102Periodontal disease, human immunodeciency virus and, 160, 161fPeriodontal pathology, 93–107aggressive periodontitis, 104, 105fdrug-induced gingival overgrowth (drug-related gingival hyperplasia), 100, 101fforeign body gingivitis, 98, 99fgingival bromatosis, 98, 99fgingivitis, 94, 95flocalized juvenile spongiotic gingival hyperplasia, 94, 95fnecrotizing ulcerative gingivitis, 96, 97fPapillon-Lefèvre syndrome, 104, 105fpericoronitis, 102–104, 103fperiodontal abscess, 102periodontitis, 102, 103fplasma cell gingivitis, 96, 97fPeriodontitis, 102, 103faggressive, 104, 105fPeriostitis, proliferative, 90, 91fPeriostitis ossicans. see Proliferative periostitisPeripheral ameloblastoma, 436, 437fPeripheral giant cell granuloma, 314, 315fPeripheral odontogenic broma, 450, 451fPeripheral ossifying broma, 312, 313f, 450Periungual bromas, in tuberous sclerosis, 470, 471fPerlèche. see Angular cheilitisPermanent makeup, 192Pernicious anemia, 512, 513fPetechiae, 186, 187ffrom fellatio, 188, 189fPeutz-Jeghers syndrome, 468, 469fPheochromocytomas, of adrenal gland, 322Phosphate-regulating gene with endopeptidase activity on the X chromosome (PHEX), 516Phycomycosis, 134Physical and chemical injuries, 169–203amalgam tattoo, 190, 191fantral pseudocyst, 194, 195fcharm needles, 192, 193fchemical burns, 176, 177fchemotherapy-induced oral mucositis, 176–178, 177fchronic lip ssure, 184, 185fcosmetic llers, 188, 189fdrug-induced pigmentation, 196, 197felectrical burns, 174, 175fexfoliative cheilitis, 184, 185fintentional tattoos, 192, 193flinea alba, 170, 171fmedication-related osteonecrosis of the jaws, 180, 181f“meth mouth”, 182, 183fminocycline-induced pigmentation, 196, 197fmorsicatio, 170, 171fmucosal or submucosal hemorrhage, 186, 187fopioid-induced palatal perforation, 182–184, 183foral ulceration with bone sequestration, 182, 183fosteoradionecrosis, 178–180, 179fpetechiae from fellatio, 188, 189fradiation-induced oral mucositis, 178, 179fsmoker’s melanosis, 198, 199fsurgical ciliated cyst, 194, 195fthermal burns, 174, 175ftraumatic granuloma, 172, 173ftraumatic ulcer, 172, 173fulceration from cunnilingus, 188, 189fxerostomia-related caries, 178, 179fPigmentationdrug-induced, 196, 197fminocycline-induced, 196, 197fPilar cyst, 28, 29fPindborg tumor, 442, 443fPlasma cell gingivitis, 96, 97fPlasmacytoma, 362, 363fPlasminogen deciency, 354, 355fPleomorphic adenoma, 284, 284f–285fcarcinoma ex, 292, 293fPleomorphic rhabdomyosarcoma, 336Plunging ranula, 276, 277fPolyangiitis, granulomatosis with, 216, 217fPolymorphous (low-grade) adenocarcinoma, 292, 293fPolyostotic brous dysplasia, 382Port wine stains, 328Port wine vascular malformation, 332, 333fPostherpetic neuralgia, 150Postoperative maxillary cyst. see Surgical ciliated cystPregnancy tumors, 310Primary adrenal insuciency. see Addison diseasePrimary hyperparathyroidism, 518Primary syphilis, 116, 117fProgressive hemifacial atrophy, 32, 33fProliferative periostitis, 90, 91fProliferative verrucous leukoplakia, 244, 244f–245fProtozoal infections, 125–139leishmaniasis, 136, 137fPseudoepitheliomatous hyperplasia, 306Pseudomembranous candidiasis, 126, 126f–127fPsoriasis, 496, 497fPTEN (phosphatase and tensin homologue deleted on chromosome 10) gene, mutations in, multiple hamartoma syndrome and, 472Pulpdisease of, 79–92stones in, 80, 81fPulpitis, hyperplastic, 80, 81fPurpura, 186Pyogenic granuloma, 310, 310f–311fPyostomatitis vegetans, 524, 525fRRadiation-induced oral mucositis, 178, 179fRadicular cyst, 86, 87fRamsay Hunt syndrome, 150, 151fRanula, 274, 276, 277fReactive subpontine exostosis, 18, 19fRecurrent aphthous stomatitis, 206Recurrent intraoral herpes, 146, 147fReduced enamel epithelium, 412Regional ileitis. see Crohn diseaseRegional odontodysplasia, 74, 75fRenal osteodystrophy, 520, 521fResidual periapical cyst, 86, 87fResorptionexternal, 50, 51finternal, 50, 51fRespiratory implantation cyst. see Surgical ciliated cystReticular hyperpigmentation, in dyskeratosis congenita, 464Reticular hypopigmentation, in dyskeratosis congenita, 464Retrocuspid papilla, 302Rhabdomyoma, 326, 327fRhabdomyosarcoma (RMS), 336, 337fRickets, 514, 515fRiga-Fede disease, 58RUNX2 gene, 370SSalivary adenocarcinoma, not otherwise specied, 294, 295fSalivary duct cyst, 276, 277fSalivary gland disease, HIV-related, 162Salivary gland pathology, 273–297acinic cell carcinoma, 286, 287fadenoid cystic carcinoma, 290, 290f–291fcanalicular adenoma, 286, 287fcarcinoma ex pleomorphic adenoma, 292, 293fcheilitis glandularis, 280, 281fintraosseous mucoepidermoid carcinoma, 288, 289fmucocele (mucus extravasation phenomenon), 274, 274f–275fmucoepidermoid carcinoma, 288, 289fnecrotizing sialometaplasia, 282, 283fpleomorphic adenoma (benign mixed tumor), 284, 284f–285fpolymorphous (low-grade) adenocarcinoma, 292, 293franula, 276, 277fsalivary adenocarcinoma, not otherwise specied, 294, 295fsalivary duct cyst, 276, 277fsecretory carcinoma, 294, 295fsialadenitis, 280, 281fsialadenosis, 280, 281fsialolithiasis, 278, 278f–279fSjögren syndrome, 282, 283fWarthin tumor (papillary cystadenoma lymphomatosum), 286, 287fSarcoidosis, oral, 212, 213fSarcomatoid carcinoma, 262, 263fSchwannoma, 316, 317fSchwannomatosis, 316Sclerosing osteomyelitis, 90, 91fSclerosissystemic, 494, 494f–495ftuberous, 470, 471fScurvy, 508, 509fSebaceous hyperplasia, 230–232, 231fSeborrheic keratosis, 230, 231fSecondary hyperparathyroidism, 518Secondary syphilis, 116, 117fSecretory carcinoma, 294, 295fSegmental odontomaxillary dysplasia, 36, 37fSelf-inicted wounds, 172Sézary syndrome, 360Shagreen patches, in tuberous sclerosis, 470Shell teeth, 72Shingles, 150, 150f–151fShovel-shaped incisors, 62, 63fSialadenitis, 280, 281fSialadenosis, 280, 281fSialolithiasis, 278, 278f–279fSialometaplasia, necrotizing, 282, 283fSialo-odontogenic cyst, 428, 429fSicca syndrome, 282Simple bone cyst, 380, 381fSinonasal papillomas, 226–228, 227fSinus, cutaneous, 82, 83fSinusitis, 120, 121fSjögren syndrome, 282, 283fSmokeless tobacco keratosis, 248, 249fSmoker’s melanosis, 198, 199fSmoker’s palate, 238, 239fSnu Dipper’s lesion, 248, 249fSo tissue tumors, 299–347aggressive bromatosis, 308, 309fangiosarcoma, 338, 339fcongenital epulis, 326, 327f 534 Index epulis ssuratum, 304, 304f–305fepulis granulomatosa, 312, 313fbroma, 300, 300f–301fgiant cell broma, 302, 303fgranular cell tumor, 324, 325fhemangioma and vascular malformations, 328, 329finammatory papillary hyperplasia, 306, 307fintrabony vascular malformation, 330, 331fKaposi sarcoma, 340, 341fleaike denture broma, 306, 307fleiomyoma, 326, 327fleiomyosarcoma, 338, 339flipoma, 314, 315flymphatic malformation, 334, 335fmelanotic neuroectodermal tumor of infancy, 324, 325fmetastatic tumors, of oral so tissues, 342, 343fmultiple endocrine neoplasia type 2B, 322, 322f–323fmyobroma, 308, 309fneurobroma, 318, 319fneurobromatosis type I, 320, 320f–321foral focal mucinosis, 302, 303fosseous choristoma, 328, 329fpalisaded encapsulated neuroma, 318, 319fperipheral giant cell granuloma, 314, 315fperipheral ossifying broma, 312, 313fport wine vascular malformation, 332, 333fpyogenic granuloma, 310, 310f–311frhabdomyoma, 326, 327frhabdomyosarcoma, 336, 337fschwannoma, 316, 317fsolitary brous tumor, 308, 309fSturge-Weber syndrome, 332, 333ftraumatic neuroma, 318, 319fSolar lentigines, 234, 235fSolitary bone cyst. see Simple bone cystSolitary circumscribed neuroma, 318, 319fSolitary brous tumor, 308, 309fSpindle cell carcinoma, 262, 263fSpindle cell-sclerosing rhabdomyosarcoma, 336Split papules, 116Spontaneous sequestration. see Oral ulceration with bone sequestrationSquamous cell carcinoma, oral and oropharyngeal, 251f, 254–255, 256f–261fSquamous odontogenic tumor (SOT), 442, 443fSquamous papilloma, 224, 225fStafne defect, 24, 24f–25fStaining, of teethextrinsic, 52, 53fintrinsic, 52, 53fStatic bone cyst, 24, 24f–25fStevens-Johnson syndrome, erythema multiforme and, 482Stomatitischronic ulcerative, 490, 491fin pellagra, 510Stomatitis medicamentosa, 218Stomatitis venenata, 210, 211fStones, pulp, 80, 81fStrawberry gingivitis, 216Strawberry hemangioma, 328Sturge-Weber syndrome, 332, 333fStylocarotid syndrome, 22, 23fStylohyoid syndrome, 22, 23fSubacute cutaneous lupus erythematosus (SCLE), 492Submucosal hemorrhage, 186, 187fSubmucous brosis, oral, 250, 251fSubpontic osseous hyperplasia, 18, 19fSupercial mucocele, 274, 275fSupernumerary roots, 68, 69fSupernumerary tooth, 56Surgical ciliated cyst, 194, 195fSurgical implantation cyst. see Surgical ciliated cyst“Surgical mumps”, 280Susuk. see Charm needlesSutton disease, 206, 207fSyphilis, 116congenital, 118, 119fprimary, 116, 117fsecondary, 116, 117ftertiary, 116, 117fSystemic disease, oral manifestations of, 505–528Addison disease, 520, 521famyloidosis, 508, 509fCrohn disease, 522, 523fdiabetes mellitus, 522, 523fhyperparathyroidism (HPT), 518, 518f–519fhypophosphatasia, 516–518, 517firon deciency anemia, 510, 511fjaundice, 506, 507flipoid proteinosis, 506, 507fpellagra, 510, 511fpernicious anemia, 512, 513fpyostomatitis vegetans, 524, 525frenal osteodystrophy, 520, 521frickets, 514, 515fscurvy, 508, 509furemic stomatitis, 524, 525fvitamin D-resistant rickets, 516, 517fxanthelasma, 508, 509fSystemic lupus erythematosus (SLE), 492Systemic sclerosis, 494, 494f–495fTTalon cusp, 62, 63fTattoosamalgam, 190, 191fintentional, 192, 193fTaurodontism, 66, 67fT-cell lymphoma, nasal type, 360, 361fTeethdiscolorations of, 52double, 60, 60f–61fghost, 74natal, 58, 59fneonatal, 58pathology of, 41–78shell, 72staining ofextensive, 52, 53fintrinsic, 52, 53fsupernumerary, 56wear, 46Telangiectasia, hereditary hemorrhagic, 468, 469fTertiary hyperparathyroidism, 518Tertiary syphilis, 116, 117falassemia, 352, 353fermal burns, 174, 175frombocytopenia, 354–356, 355frombotic thrombocytopenic purpura (TTP), 356“rush.” see Pseudomembranous candidiasisyroglossal duct cyst, 30, 31fyroglossal tract cyst, 30, 31fTobacco pouch keratosis, 248, 249fTonguecoated, 12ssured, 10, 11fhairy, 12, 12f–13fTonsillar crypts (tonsillar surface invaginations), 110Tonsillitis, 110, 111fTonsilloliths, 111fToothpaste, allergic contact stomatitis to, 210, 211fTorus mandibularis, 20, 20f–21fTorus palatinus, 22, 23fToxic epidermal necrolysis, erythema multiforme and, 482Transient lingual papillitis, 210, 211fTransposition, dental, 54, 55fTraumatic bone cyst. see Simple bone cystTraumatic ciliated cyst. see Surgical ciliated cystTraumatic broma, 300, 300f–301fTraumatic granuloma, 172, 173fTraumatic neuroma, 318, 319fTraumatic ulcer, 172, 173fTraumatic ulcerative granuloma with stromal eosinophilia. see Traumatic granulomaTrench mouth. see Necrotizing ulcerative gingivitisTreponema pallidum, 116Trichilemmomas, in multiple hamartoma syndrome, 472Tricho-dento-osseous syndrome, 68, 69fTuberculosis, 112–114, 113fTuberous sclerosis, 470, 471fTurner hypoplasia, 42, 43fTyndall eect, in blue nevus, 236UUlcerfrom cunnilingus, 188, 189feosinophilic. see Traumatic granulomatraumatic, 172, 173fUnicameral bone cyst. see Simple bone cystUnicystic ameloblastoma, 436, 437fUremic stomatitis, 524, 525fUvula, bid, 2, 3fVVan der Woude syndrome, 4, 5fVanishing bone disease, 374, 375fVaricella, 148, 149fVaricella-zoster virus (VZV), 150Varices, 14, 15fVaricosities, 14, 15fVascular malformations, 328, 329fintrabony, 330, 331fVascular tumors, 328Verruca vulgaris, 224, 225fVerruciform xanthoma, 228, 229fVerrucous carcinoma, 262, 263fVerrucous leukoplakia, proliferative, 244, 244f–245fVincent infection. see Necrotizing ulcerative gingivitisViral infections, 141–168acquired immunodeciency syndrome-related Kaposi sarcoma, 158, 158f–159facute herpetic gingivostomatitis, 142, 142f–143fchronic intraoral herpes, 146, 147fhand-foot-and-mouth disease, 152, 153fherpangina, 152, 153fherpes labialis, 144, 145fherpes zoster (shingles), 150, 150f–151fherpetic whitlow, 144, 145fhuman immunodeciency virus (HIV), 154aphthous stomatitis, 162, 163fhistoplasmosis, 162–164, 163fand human papillomavirus-related lesions, 156, 157flymphadenopathy, 162, 163flymphoma, 164, 165foral candidiasis, 154, 154f–155foral hairy leukoplakia, 156, 157foral/head and neck squamous cell carcinoma, 164, 165fand periodontal disease, 160, 161finfectious mononucleosis, 148, 149frecurrent intraoral herpes, 146, 147fvaricella (chickenpox), 148, 149fVisceral leishmaniasis, 136Vitamin B3, 510Vitamin B12, 512Vitamin C (ascorbic acid), 508Vitamin D, 514Vitamin D-resistant rickets, 516, 517fVitamin D3, 514von Willebrand disease, 352WWaldeyer ring, 110Wart, common, 224, 225fWarthin tumor, 286, 287fWarty dyskeratoma, 466, 467fWegener granulomatosis, 216, 217fWhite line. see Linea albaWhite sponge nevus, 458, 459fXXanthelasma, 508, 509fXeroderma pigmentosum, 464, 465fXerostomia-related caries, 178, 179fZZygomycosis, 134So tissue tumors (Continued) Syphilis (Continued)

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