Oral Manifestations of Systemic Diseases and Their Treatments 1563

addition, the authors concluded that the effective- disease. Dental professionals must be sufficiently
ness of adjuvant therapy to corticosteroids familiar with clinical oral manifestation of
requires further validation. vesiculobullous diseases to ensure early diagnosis
Several reports recommend the use of topical and treatment, since this in turn determines the
corticosteroids alone in localized and mild disease prognosis and course of the disease.
and topical corticosteroids or systemic predniso- Patients with vesiculobullous diseases often
lone (0.5 mg per kg per day) in moderate and require special care during dental appointments to
widespread disease (Joly et al. n.d.). manage sensitive areas of the mouth and prevent
Other reports suggest the use of dapsone, future blisters from forming. If active disease is
chlorambucil, azathioprine, methotrexate, present, gentle tissue handling is required to ensure
mycophenolic acid, and tetracyclines. Some minimal disruption of the affected mucosa.
have advocated the use of plasmapheresis, high Oral blisters and ulcers can be very painful,
dose intravenous immunoglobulin, immunoad- making it difficult to perform home oral hygiene
sorption, or rituximab in refractory disease measures. In addition, patients may be restricted to
(Kjellman et al. n.d.; Schmidt et al. n.d.). a soft diet. As a result, patients may have an
Management of MMP usually involves the use increased risk of developing dental caries and peri-
of potent topical corticosteroids in combination in odontal disease. Oral hygiene instructions should
low-risk patients that have lesions limited to the be tailored to the level of mucosal involvement.
mouth, with or without cutaneous involvement. When significant disease is present, gentle home
Some advocate the additional use of a tetracycline care such as the use of extra-soft toothbrushes,
or dapsone in this group. If unresponsive, systemic mildly flavored toothpastes, and nonalcohol
prednisolone (0.5 mg per kg per day) may be intro- containing mouth rinse should be recommended.
duced, with azathioprine or mycophenolic acid Active autoimmune vesiculobullous diseases
used as “steroid-sparing” agents (Chan et al. 2002). are generally managed with a combination of
In patients who are deemed high risk (with mul- long term topical and/or systemic immunosup-
tiple mucosal site involvement) with severe disease pressant medications. The most common group
or rapid progression, prednisolone (1–1.5 mg per of these medications is corticosteroids. Potential
kg per day) and additional cyclophosphamide systemic adverse effects of corticosteroids include
(1–2 mg per kg per day orally or 500–1000 mg development or worsening of osteoporosis, hyper-
intravenously every 3–4 weeks) or mycophenolic tension, increased appetite, susceptibility to infec-
acid has been recommended (Chan et al. 2002; tion, gastroesophageal reflux, diabetes mellitus,
Kirtschig et al. 2003; Kirtschig et al. 2010). adrenal suppression, and cushingoid features.
Favorable results have been found with the use Specific to the oral cavity, long term use of topical
of cyclophosphamide (2 mg per kg per day), dap- corticosteroids may predispose patients to the
sone (in mild disease), mycophenolic acid, and development of opportunistic infections such as
intravenous immunoglobulin in combination oral candidosis, as well as mucosal atrophy.
with prednisolone (Kirtschig et al. 2003). In
refractory disease, rituximab and intravenous
immunoglobulin have been shown to be effective Gastrointestinal Disorders
(Letko et al. 2004; Le Roux-Villet et al. 2011).
Celiac Disease
Dental Considerations
Dental considerations for pemphigus and Introduction
pemphigoid are similar and will be covered here Celiac disease (CD) is a chronic autoimmune
together. An important aspect of patient manage- disorder of the small intestine triggered by the
ment for both pemphigus and pemphigoid is early ingestion of gluten. It appears in genetically pre-
diagnosis when lower doses of medication can be disposed patients. The clinical spectrum of CD is
used for shorter periods of time to control the varied and includes the classic presentation of
1564 S.-C. Yeoh et al.

malabsorption with diarrhea, nonclassical extra- enzyme normally involved in collagen cross-
intestinal features, subclinical or asymptomatic linking and tissue remodeling. De-amidation of
forms, and potential disease characterized by pos- the gliadin peptide allows for high-affinity binding
itive serology with a normal intestinal mucosa on to the celiac-associated HLA peptides (DQ2 or
biopsy. DQ8) found on antigen-presenting cells and acti-
vation of helper T (Th) cells (Dieterich et al. 1997).
Epidemiology For this reason, people must carry either
The prevalence of CD in western populations has HLA-DQ2 (95% of patients with celiac disease)
been reported to be close to 1% in the general or -DQ8 (5% of patients with celiac disease) to
population in the United States and 1.5% in the develop celiac disease. Stimulation of Th cells
United Kingdom and Scandinavia. In patients at leads to cell death and tissue remodeling with
risk, the prevalence is even higher, for example, villous atrophy and crypt hyperplasia induced by
3–6% in type I diabetes mellitus and up to 20% in Th1-derived cytotoxic T lymphocytes. Th2 trig-
first-degree relatives of celiac patients. Thus, gers plasma cell maturation and subsequent anti-
approximately one in 100 of the population is gliadin and anti-tTG antibody production
affected (Catassi et al. 2014). (Dieterich et al. 2003).

Etiopathogenesis Clinical-Pathologic Features

Celiac disease is an immune-mediated systemic The clinical spectrum of CD is varied and may
condition elicited by gluten and related prola- include chronic diarrhea with abdominal disten-
mines in genetically predisposed individuals. It sion, nausea, vomiting, fatigue, and malaise.
is characterized by a variable combination of The common modes of presentation in children
gluten-induced signs and symptoms, specific anti- are recurrent abdominal pain, failure to thrive and
bodies, a specific human leukocyte antigen (HLA) short stature, and the screening of high risk groups
type (DQ2 or DQ9), and enteropathy. There is a (Reilly et al. 2011). A diarrhea predominant presen-
clinical and histological improvement on a strict tation currently occurs in only 10% of children and
gluten-free diet and relapse when dietary gluten is tends to be most prominent in those who are very
reintroduced. young at diagnosis (Reilly et al. 2011). Children
Loss of immune tolerance to gliadin peptide diagnosed through screening generally have family
antigens derived from wheat, rye, barley, and members with CD or have an autoimmune disease
related grains is the central abnormality of celiac such as type 1 diabetes mellitus or thyroid disease.
disease. These peptides remain intact in the small Children may be overweight or obese at diagnosis.
intestinal lumen due to their resistance to prote- Diarrhea remains one mode of presentation
ases (Shan et al. 2002). These intact peptides are prompting testing for CD in adults; however, the
thought to gain access to the lamina propria via majority of adults present with one of the many
faulty tight junctions, endothelial cell trans- “nonclassic symptoms” such as anemia (usually
cytosis, sampling of the intestinal lumen by den- as a result of iron deficiency, although it may be
dritic cells, and passage during resorption of caused by chronic disease) (Harper et al. 2007),
apoptotic villous enterocytes. osteoporosis, and various other conditions includ-
In the intestinal submucosa, these peptides ing dermatitis herpetiformis, abdominal pain
trigger both innate and adaptive immune (Sanders et al. 2005), neurological or psychiatric
responses. Gluten peptides are able to stimulate problems (Hadjivassiliou et al. 2014), aphthous
interleukin-15 production by dendritic cells and stomatitis (Volta et al. 2014), and vitamin defi-
macrophages, which, in turn, stimulate ciencies (Lebwohl et al. 2015).
intraepithelial lymphocytes, leading to epithelial The diagnosis of CD usually involves serolog-
damage (Mention et al. 2003; Raki et al. 2006). ical testing for transglutaminase-IgA (tTG-IgA)
In the submucosa, gluten peptides are and deaminated gliadin peptide-IgG (DGP-IgG)
de-amidated by tissue transglutaminase (tTG), an or transglutaminase-IgA (tTG-IgA) with total IgA
Oral Manifestations of Systemic Diseases and Their Treatments 1565

level (to exclude the 2–3% of people with celiac

disease who are IgA deficient), and IgA endo-
mysial antibodies. HLA-DQ2/8 genotyping may
be performed on blood or buccal scrapes (Rubio-
Tapia et al. 2013).
The gold standard for diagnosis still remains
the small intestinal biopsy, demonstrating villous
atrophy.

Oral Manifestations
Several oral conditions have been reported to be
associated with CD. The prevalence of recurrent
aphthous ulceration in patients with CD has been
reported to be significantly higher than in the
general population (Fig. 37). Studies have also
described permanent teeth enamel defects in a
high percentage of celiac patients (Fig. 38), Fig. 37 28-year-old female with a 9 year history of recur-
rent oral ulceration. Each ulcer lasting 2–3 weeks, then
which are systematically and chronologically
healing spontaneously as a new ulcer formed. Patient
distributed in all four quadrants of the dentition reported a history of frequent bloating and diarrhea. Sub-
(Aine et al. 1990; Priovolou et al. 2004; sequent testing for celiac disease and inflammatory bowel
Bucci et al. 2006; Shakeri et al. 2009; Cheng disease confirmed that the patient had positive celiac
serology
et al. 2010).

Patient Management
At present, a strict life-long gluten-free diet is 1900s; however in 1986, one study provided the
the only available effective treatment of CD. In strongest evidence that dental enamel defects may
reality, complete avoidance of gluten is difficult be an extra-intestinal manifestation of CD (Aine
due to hidden gluten in food contaminants. In 1986). In this study, defects were described as
2011, the United States Food and Drug Admin- “systematic” as they presented symmetrically
istration set the limit of <20 ppm gluten (equiv- and chronologically in all four quadrants. This
alent to 10 ppm gliadin) for gluten-free foods. It was reflective of the period that disruption of
has been estimated that the threshold of pro- amelogenesis occurred. Defects may affect decid-
longed gluten ingestion in some individuals uous or permanent teeth. A grading system to
with CD may be less than 50 mg/d (Catassi classify the severity of the CD-related enamel
et al. 2007). lesions, from simple opacities to severe structural
defects was proposed.
Dental Considerations
During enamel matrix deposition and calcifica- • Grade I: Defect in color of enamel
tion, genetic and/or environmental factors can Single or multiple creams, yellow or brown
cause dental enamel defects, which may be quan- opacities with clearly defined or diffuse mar-
titative or qualitative. Disturbances in matrix gins; a part or the entire surface of enamel is
secretion can cause enamel hypoplasia, presenting without glaze
as deficiency of enamel quantity, whereas qualita- • Grade II Slight structural defects
tive defects present as enamel opacity and are due Enamel surface rough, filled with horizontal
to disruptions occurring during the calcification grooves or shallow pits; light opacities and
phase of enamel formation. discoloration may be found; a part or the entire
A link between enamel defects and gastroin- surface of enamel is without glaze
testinal diseases were first noted in the early • Grade III Evident structural defects
1566 S.-C. Yeoh et al.

Fig. 38 Celiac disease. 12-year-old male with gluten atrophic squamous epithelium disrupted by exocytosis and
intolerance presents with Grade 1 enamel defects (a). intraepithelial edema (c). Prominent mixed inflammation
Note also the presence of erythematous spongiotic gingiva was seen within the lamina propria, but no eosinophils or
associated with the upper right canine (13) and left lateral granulomas were seen. (Hematoxylin and eosin stain).
incisor (22). A close-up of the lesion associated with 13 is (Images courtesy of Professor Camile Farah, Perth Oral
noted in (b). Histopathology of the gingival lesions showed Medicine & Dental Sleep Centre, Perth WA, Australia)

A part or the entire surface of enamel rough The precise cause of these enamel defects
and filled with deep horizontal grooves that remains unclear. It is hypothesized that a gluten-
vary in width or have large vertical pits; large induced immunological process occurs between
opacities of different colors or strong discolor- 6 months and 7 years in the enamel-producing
ation may be in combination organ resulting in defective enamel formation. The
• Grade IV Severe structural defects celiac-type enamel lesions, like the celiac disease
The shape of the tooth changed: the tips of itself, were strongly associated with the HLA allele
cusps are sharp-pointed and/or the incisal DR3 (Mariani et al. 1994). The distribution of
edges are unevenly thinned and rough; the defects also closely correlates with age of diagnosis
thinning of the enamel material is easily and linked to stages of odontogenesis occurring at
detectable and the margins of the lesions are the time of active/undiagnosed CD. Permanent inci-
well defined; the lesion may be strongly sors are the most commonly affected, followed by
discolored. molars, canines then premolars.
Oral Manifestations of Systemic Diseases and Their Treatments 1567

Early diagnosis and preventive care are essen- and reappearance of recurrent ulcers coinciding with
tial for the successful management of develop- the reintroduction of gluten (Bucci et al. 2006).
mental enamel defects. Children with a family Various management strategies have been
history of CD should be assessed for enamel described in an attempt to ameliorate or induce
defects as soon as the teeth erupt. The main prob- remission of aphthous-like ulceration in patients
lems associated with enamel hypoplasia are with CD. These include the use of topical cortico-
compromised esthetics, tooth sensitivity, and steroids and systemic medications such as
increased risk for caries and tooth wear. pentoxifylline, doxycycline, zinc sulfate, colchi-
Children with extensive enamel defects usually cine, clofazimine, prednisone, montelukast
require interdisciplinary management possibly sodium, sulfones, thalidomide, methotrexate,
involving extraction, complex restorations, or cyclosporin, chlorambucil, infliximab, etanercept,
orthodontics. In cases with high caries risk, neu- interferon -α, azathioprine, and levamisole.
tral sodium fluoride gels or varnishes applied pro-
fessionally 3 or 6 monthly may be recommended.
In addition, calcium and phosphate rich agents Inflammatory Bowel Disease
such as casein phosphopeptide-amorphous cal-
cium phosphate (CPP-ACP) can facilitate the Introduction
remineralization of hypomineralized areas and Inflammatory bowel disease (IBD) consists of two
early carious lesions on the tooth surface of teeth well-established but not entirely separate disease
with enamel defects. entities, Crohn’s disease (CrD), and ulcerative coli-
Defective enamel is structurally weak and eas- tis (UC). The mechanism behind IBD involves an
ily deteriorates under masticatory forces, possibly uncontrolled immune-mediated inflammatory
leading to marginal leakage around existing res- response in genetically predisposed individuals to
torations, recurrent caries, and pulp involvement. an unknown environmental trigger that interacts
Restorative materials that bond to both dentin and with the intestinal flora and can affect any part of
enamel such as resin modified glass-ionomer the gastrointestinal tract (Loftus 2004).
cements and polyacid modified composite resins Although UC and CrD are generally consid-
are likely to be more successful for restoration of ered as clinically distinct conditions with separate
teeth with enamel defects. Although composite clinical, anatomical, and histological findings,
resins offer excellent esthetics, direct adhesion of they probably represent a continuum of diseases,
these materials to teeth with minimal or poorly with UC and CrD at either extreme. Moreover,
mineralized enamel is usually difficult to achieve. there is likely a spectrum of illnesses within each
Stainless steel crowns are highly durable for disorder.
restoring and protecting both primary and perma-
nent molars affected by enamel hypoplasia. Com- Epidemiology
plete tooth coverage restorations reduce tooth The annual incidence in North America of both
sensitivity, prevent cusp fractures, and help main- CrD and UC is very similar and estimated to be
tain space and crown height. between 0 and 20 per 100,000 population. The
Studies have shown an increased prevalence of prevalence of both conditions is also thought to be
recurrent aphthous-like ulceration in patients with similar in North America, with estimates of
CD compared with the general population (Aydemir 25–300 per 100,000 for CrD and 35–250 per
et al. 2004; Bucci et al. 2006). Support for the 100,000 for UC (Molodecky et al. 2012).
correlation between CD and recurrent aphthous- Although CrD and UC may occur at any age,
like ulceration is provided by the observation that the peak age of onset for CrD is between 20 and
a gluten-free diet is effective management of the 30 years of age and between 30 and 40 years for
ulcers. Several groups have reported significant UC. There appears to be a second peak, especially
improvement, if not complete remission, of oral for UC between 60 and 70 years of age
ulceration in most CD patients on gluten-free diets, (Molodecky et al. 2012). There is no significant
1568 S.-C. Yeoh et al.

difference in incidence and prevalence between its effect on UC, smoking appears to increase the
men and women for both conditions risk of CrD and is associated with a higher rate of
(Ananthakrishnan 2015). IBD is more prevalent postoperative disease (Cosnes 2004).
among Ashkenazi Jews compared with the gen- Patients with IBD appear to mount an abnormal
eral population, with estimates of prevalence or exaggerated immune response to various trig-
being 17 and 80 per 100,000 among the Ashke- gers, resulting in inflammatory injury. HLA class II
nazi in Israel (Ananthakrishnan 2015). Up to 15% molecules that mediate autoimmune injury are
of persons with IBD (both CrD and UC) have a found in high numbers within the intestinal epithe-
first-degree relative who also has IBD. The life- lial cells of patients with active IBD. Activated
time risk of developing IBD in first-degree rela- macrophages secrete increased amounts of
tives has been estimated at 5% in CrD and about pro-inflammatory cytokines within the lamina pro-
2% in UC among non-Jewish populations and 8% pria of the intestinal wall. There also appears to be
and 5% among Jewish populations respectively. decreased production of several down-regulatory
In children and siblings, the risk is approximately cytokines, perpetuating the chronic inflammation
8% in both CrD and UC (Ananthakrishnan 2015). in these patients (Zhang and Li 2014).
There is a reported increased mortality associ- Genetic predisposition is another well-accepted
ated with CrD compared with the general risk factor for the development of IBD, with up to
population, with surgical complications and 15% of persons with IBD having a first-degree
malnourishment as the major causes of direct relative who also has IBD. In CrD, the concordance
CrD-related mortality. No definitive evidence rates among monozygotic and dizygotic twins are
has been found to suggest a higher mortality 50% and 10% respectively, which is suggestive of
among patients with UC compared with the gen- significant but not complete genetic predisposition.
eral population (Jess et al. 2013). In UC, the concordance rates among monozygotic
and dizygotic twins are 16% and 4% respectively
Etiopathogenesis (Zhang and Li 2014).
IBD can be categorized into two major forms, There has been a suggestion that external envi-
CrD and UC. CrD may cause transmural inflam- ronmental triggers interact with the intestinal flora
mation and affect any part of the gastrointestinal within the internal environment to cause disease.
tract in a noncontinuous pattern, most commonly, Patients with IBD have been shown to have a
the terminal ileum, or the perianal region. CrD is reduced diversity of gut microbiota. In addition
commonly associated with complications such as to gut bacteria, it is assumed that viruses and fungi
abscesses, fistulas, and strictures. In contrast, UC may also play a role in the pathogenesis of IBD
is typified by mucosal inflammation limited to the (Joossens et al. 2011).
colon. Although the etiology of IBD remains Diet appears to influence the development of
largely unknown, recent research has indicated IBD, with the incidence of these conditions
that an individual’s genetic susceptibility, external appearing to be higher in patients who have a
environment, intestinal microbial flora, and diet high in refined carbohydrates, and less dietary
immune responses are all involved and function- fiber, raw fruit, and vegetables compared with
ally integrated in the pathogenesis of IBD (Zhang healthy controls.
and Li 2014). Lifestyle factors that have been noted to be
Various environmental triggers have been impli- influential in the development of IBD include
cated in the pathogenesis of IBD, including stress, anxiety, and depression, as well as seden-
smoking, diet, drugs, geography, social stress, and tary behavior.
psychological elements (Loftus 2004). Among Risk factors for colorectal cancer in IBD
these, smoking remains the most widely studied include persistent active inflammation and immu-
and replicated environmental trigger for IBD. nosuppression followed by long-standing disease,
There appears to be an inverse association between extensive disease, young age at diagnosis, family
the development of UC and smoking. Contrary to history of colorectal cancer, and coexisting
Oral Manifestations of Systemic Diseases and Their Treatments 1569

primary sclerozing cholangitis. The risk of extra- During a severe attack, patients may experi-
intestinal cancers, including lymphoproliferative ence fever, tachycardia, dehydration, and toxicity.
as well as skin cancers, is significantly higher Pallor may also be observed reflecting anemia.
among patients with IBD compared with the gen- Toxic megacolon is a medical emergency.
eral population (Zhang and Li 2014). Patients appear septic; have high fever, lethargy,
chills, and tachycardia; and have increasing
Clinical-Pathologic Features abdominal pain, tenderness, and distention.
Common clinical features of IBD include recurrent There is no single test that confirms the diagnosis
abdominal pain, cramping, irregular bowel habits, of IBD. The diagnosis of IBD is made from the
diarrhea, and passage of mucus without blood. summation of findings of a physical examination,
Systemic symptoms are common and include patient history and various tests, including blood
weight loss, fever, sweats, malaise, and arthralgias. tests, stool tests (especially fecal calprotectin),
Fatigue is often related to the pain, inflammation, endoscopy, biopsies, and imaging studies.
and anemia that accompany disease activity. Chil- Blood tests are not specific for IBD but may
dren may present with growth retardation and be performed to detect and evaluate the severity
delayed or failed sexual maturation. Some patients of inflammation, anemia, and vitamin or
also present with extraintestinal manifestations, mineral deficiencies associated with IBD. Anti-
including arthritis, uveitis, or liver disease. Saccharomyces cerevisiae antibody (ASCA) and
Grossly, loosely formed bloody stools, occa- atypical perinuclear antineutrophil cytoplasmic
sionally with tenesmus, although typical of UC, antibodies (p-ANCA) serological tests can help
are less common in CrD. Fifty percent of patients discriminate CrD from UC in some situations.
with CrD may present with perianal disease such as Fecal calprotectin is the most widely used neu-
fistulas and abscesses (American Gastroenterolog- trophil derived protein biomarker and is a highly
ical Association Clinical Practice Committee sensitive, noninvasive marker of intestinal inflam-
2003). Some patients with CrD also develop a mation. It is used for differentiating between peo-
mass in the right colon. Weight loss is noted more ple with and without current inflammation in the
commonly in CrD than in UC, secondary to mal- lower gut needing further evaluation and for mon-
absorption associated with small bowel disease. itoring patients with IBD on therapy to determine
The World Gastroenterology Organization whether there is current disease activity, risk of
(WGO) indicates the following symptoms may relapse, and/or response to current type and dose
be associated with inflammatory damage in the of treatment.
digestive tract: Endoscopy/colonoscopy with histology and
radiology are all used to establish the diagnosis
• Diarrhea: mucus or blood may be present in the of IBD and to assess its severity and extent. Cap-
stool, can occur at night, incontinence may occur. sule endoscopy is a useful modality to assess for
• Constipation: this may be the primary symp- the presence, extent, and severity of small bowel
tom in UC, when the disease is limited to the involvement in CrD.
rectum; obstipation may occur and may pro- UC primarily affects the mucosa of the large
ceed to bowel obstruction. bowel, while CrD is a transmural disease that
• Bowel movement abnormalities: pain or rectal can affect the whole gastrointestinal tract. Histo-
bleeding may be present, as well as severe logically, features of UC include severe crypt
urgency and tenesmus. architectural distortion and widespread decreased
• Abdominal cramping and pain: commonly pre- crypt density, frankly villous surface. In addition,
sent in the right lower quadrant in CrD; occur heavy diffuse transmucosal lamina propria cell
periumbilically or in the left lower quadrant in increase with diffuse basal plasmacytosis. There is
moderate to severe UC an increased intensity of the alterations towards the
• Nausea and vomiting: occurs more often in distal colon with severe mucin depletion. There
CrD than in UC may also be Paneth-cell metaplasia distal to the
1570 S.-C. Yeoh et al.

hepatic flexure. Features of CrD include the pres- Oral lesions seen in relation to inflammatory
ence of granulomas, a collection of monocyte/mac- bowel conditions can be broadly classified as
rophage cells, and other inflammatory cells with or “specific” or “nonspecific.”
without giant cells. The macrophages appear as CrD specific lesions include:
large cells with abundant pale eosinophilic cyto-
plasm and large oval nucleus arranged in clusters. • Mucosal tags (Fig. 39), usually noted in the
Because of this epithelial cell-like morphology, labial and buccal vestibules and in the
they are referred to as epithelioid cells. The cells retromolar region. Up to 75% of these lesions
may be closely packed together and have a sarcoid- may show noncaseating granulomas on histopa-
like aspect, but a “loose” expanded form of granu- thology. No direct association of these lesions
loma is more common in CrD. Associated inflam- with intestinal CrD activity has been reported.
matory cells are lymphocytes, usually CD4+ T • Cobblestoning of the buccal mucosa (Fig. 40)
cells, showing expression of CD28, the ligand for with fissured swelling and corrugation, with
the B7-related cell surface proteins CD80 (B7-1) a hyperplastic appearance. This is generally
and CD86 (B7-2). noted on the posterior buccal mucosa
Plain abdominal radiography may establish • Mucogingivitis, with the gingiva appearing
whether colitis is present and its extent in some edematous, granular, and hyperplastic, with or
cases of UC. In addition, it may give an indication without ulceration (Fig. 41). The entire height
of a mass in the right iliac fossa, or show evidence of the gingiva may be involved.
of small bowel dilatation or obstruction in CrD.
CT, ultrasound, and MRI may be helpful in deter-
mining the disease extent and severity and to
assess for perforating complications.

Oral Manifestations
Oral lesions were initially described in patients
with CrD in 1969, and since that time, there
have been various reports on the incidence of
oral lesions in IBD (Lankarani et al. 2013).
The highest rate was reported in a study of
pediatric patients with CrD, indicating a rate of
48% (Pittock et al. 2001). Most publications esti-
mate a prevalence rate between 20% and 50%
(Lourenco et al. 2010). Fig. 39 Aphthous-like ulcer and mucosal tags in Crohn’s
disease
In most cases, intestinal involvement precedes
the oral lesions. Oral lesions are more common in
CrD compared with UC. Children are more often
affected, and there appears to be a male dominance
(Lourenco et al. 2010). There is a reported increase
in prevalence of oral disease in CrD patients with
proximal gastrointestinal tract and/or perianal
involvement (Pittock et al. 2001). Oral lesions
may be the primary presenting signs preceding
gastrointestinal symptoms in 5–10% of affected
patients. Oral lesions may become more severe
during active gastrointestinal disease; however, up
to 30% of patients may continue to manifest oral
lesions despite disease control (Pittock et al. 2001). Fig. 40 Buccal cobblestoning
Oral Manifestations of Systemic Diseases and Their Treatments 1571

Fig. 41 16-year-old female with history of

Fig. 43 Pyostomatitis vegetans in patient with Crohn’s
mucogingivitis, later diagnosed with Crohn’s disease
disease

The specific lesions of CrD contain granuloma-

tous changes observed on histological examination
(Fig. 45). They are less common than nonspecific
lesions and can occur either concomitantly with
intestinal symptoms or before gut presentation by
several years. The most affected portions in the
mouth are the buccal mucosa, gingiva, lips, vestib-
ular, and retromolar areas.
Most patients with oral manifestations of CrD
are asymptomatic. In this cohort, no formal treat-
ment is required for the oral disease, and this
should resolve once the gastrointestinal disease
Fig. 42 Swelling of lower lip in patient with Crohn’s
is suppressed.
disease
There are many similarities between the oral
manifestations of CrD and UC. Although oral
lesions are more common in CrD, almost all of
the so-called nonspecific oral lesions described in
• Lip swelling with vertical fissures (Fig. 42), CrD can also occur in UC. Among these lesions,
deep linear ulcerations (usually in the buccal pyostomatitis vegetans occurs more commonly in
sulci with hyperplastic folds), and midline lip UC than in CrD (Fig. 46) (Femiano et al. 2009).
fissuring may also occur in CrD. These lesions Pyostomatitis vegetans (Fig. 46) is a chronic
also have no clear association with intestinal mucocutaneous ulcerative disorder consisting of
CrD activity. multiple miliary white or yellow pustules with an
erythematous and edematous mucosal base. Pus-
Nonspecific oral lesions include: tules may rupture and coalesce, forming “snail-
track” ulcers. Lesions most frequently involve the
• Aphthous-like ulceration (Fig. 39), reported to labial gingiva, labial mucosa, and buccal mucosa.
occur in up to 10% of patients with UC, and Pyostomatitis vegetans is most prevalent in
20–30% of those with CrD patients aged between 20 and 59 years, with an
• Pyostomatitis vegetans (Fig. 43), which may average age of 34 years. The male to female ratio
occur in CrD but more frequently in UC is 2:3. There appears to be a strong correlation
• Angular cheilitis (Fig. 44) between UC activity and pyostomatitis vegetans.
• Persistent submandibular lymphadenopathy. Histologically, features of pyostomatitis vegetans
1572 S.-C. Yeoh et al.

Fig. 44 16-year-old female presenting with swollen biopsy. (Images courtesy of Professor Camile Farah,
spongiotic upper labial gingiva (a) and angular cheilitis Queensland Oral Medicine & Pathology, Brisbane QLD,
(b) subsequently diagnosed with oral Crohn’s disease on Australia)

Fig. 45 Histological
features of cheilitis
granulomatosa with giant
cells and epitheliod cell
nodules in lamina propria
with lymphocyte infiltration

include intraepithelial and/or subepithelial micro- • Prevent complications, hospitalization, and

abscesses with neutrophils and eosinophils. surgery
Hyperkeratosis, acanthosis, and acantholysis are
also present. The mainstay of management is Initial therapy to control inflammation and allow
treatment of the underlying IBD. the gastrointestinal tract to heal includes the use of
aminosalicylates, corticosteroid, immunomodula-
Patient Management tors (such as azathioprine, 6-mercaptopurine, and
Patients with IBD require lifelong care. The goals methotrexate), and biologic agents (infliximab,
of treatment are to: adalimumab, vedolizumab, and ustekinumab).
In pediatric patients, exclusive enteral nutrition
• Treat acute disease by reducing or controlling may be used for induction of remission in CrD.
intestinal inflammation and if possible, encour- Surgery is indicated when medical therapy is
age mucosal healing unable to control symptoms, to manage mechanical
• Minimize side effects and long term adverse complications such as stricture, obstruction, perfo-
effects of the condition and eliminate symptoms ration, abscess, or refractory bleeding.
• Optimize quality of life Management of the oral manifestations of
• Correct nutritional deficiencies IBD usually involves treatment of the underlying
• Maintain steroid-free remissions intestinal disease. In severe cases with local oral
Oral Manifestations of Systemic Diseases and Their Treatments 1573

• Frequent preventive and routine dental care.

• Evaluation of hypothalamic/pituitary/adrenal
cortical function to determine the patient’s abil-
ity to undergo extensive dental procedures.
• Avoidance of nonsteroidal anti-inflammatory
drugs (NSAIDs), as they can trigger a flare-
up. The use of paracetamol is recommended,
although it can also adversely affect patients.
• Early diagnosis and treatment of oral infections.
• Diagnosis (referral and biopsy if necessary)
and treatment of oral lesions associated with
the gastrointestinal disease (Fig. 47).

Oral lesions associated with IBD generally

resolve once the gastrointestinal disease is under
control. If symptomatic, the use of topical and/or
systemic corticosteroid therapy, as well as other
immunosuppressive medications (azathioprine),
may be indicated (Fig. 48); however, liaison with
the patient’s gastroenterologist is recommended.
Fig. 46 82-year-old female with a 5 month history of oral
mucosal tenderness and swelling involving the maxillary
edentulous alveolus (a) and lower gingiva and labial
mucosa (b). Patient had been diagnosed with ulcerative
colitis several years prior, and this condition was poorly Endocrine Disorders
controlled. Biopsy of the maxillary edentulous alveolus
confirmed the diagnosis of pyostomatitis vegetans
Diabetes Mellitus

symptoms, topical and/or systemic corticoste- Introduction

roids and immunosuppressive drugs may be Diabetes mellitus (DM) is one of the most com-
indicated. mon systemic chronic conditions that the dentist
will face in a busy dental practice. The population
Dental Considerations affected by diabetes is increasing to the point that
Patients with IBD have an increased risk of devel- it is estimated that 33% of the US population will
oping dental caries and oral infection. The etiol- be affected by 2050 (Oates et al. 2013) with dia-
ogy of this increased incidence is multifactorial, betes type 2 accounting for 90–95% of all the
but appears to be related to either the patient’s cases of diabetes. These trends highlight the
altered immune status or to diet (Mancheño urgency for better understanding diabetes and to
Franch et al. 2010). provide appropriate dental care for patients with
The long-term corticosteroid regimen that diabetes. The overall goal of this section is to
many patients with IBD receive puts them at risk critically review the fundamentals of this condi-
of adrenal gland suppression. These patients may tion and the implications for the practice of
require augmentation of steroid therapy during dentistry.
dental treatments, particularly in the case of anx-
ious patients in whom preoperative or postopera- Epidemiology
tive pain management is difficult, or when a In the United States, approximately one million
complicated or stressful procedure is anticipated. people are living with type 1 diabetes and approx-
Dental management of patients with IBD imately 30,000 individuals per year are newly
should include: diagnosed (VanBuecken et al. 2000). Type