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15 Immune System Diseases
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Infectious Disease Problems
According to the Practical Guidelines for the
Appropriate Use of Antimicrobial Agents in the
Prevention of Postoperative Infections (2016),
the use of steroids and immunosuppressive drugs
is a high-risk factor for surgical site infection.
Therefore, in patients using this drug, a single
dose of amoxicillin to 48h postoperatively is recommended for invasive dental treatment such as
tooth extraction (clindamycin for patients allergic to β-lactam antibiotics).
The Problem ofSteroid Coverage
When the hypothalamic–pituitary–adrenal system is suppressed by steroids, secondary adrenal
insufciency occurs due to insufcient cortisol
production under stress conditions such as surgical invasion. In general, steroid coverage is not
necessary for local anesthesia surgery of about
1h in duration with a dose of less than 5mg/day
of prednisone equivalent. However, steroid coverage may be necessary in cases of high doses of
prednisone or depending on the degree of surgical invasion and operative time.
Problems withOsteoporosis Drugs
The rst recommended drug for steroid-induced
osteoporosis is a bisphosphonate (BP). The Japanese
Osteonecrosis of the Jaw Review Committee position paper (2016) does not recommend withdrawal
of BP before invasive dental procedures in osteoporotic patients receiving BP. On the other hand, the
American Association of Oral and Maxillofacial
Surgeons position paper (2014) advocates that
patients who have received BP for more than 4years
or who have osteoporosis with risk factors for osteonecrosis of the jaw undergo invasive dental treatment, if their general condition permits, should
discuss and consider withdrawal of BP for approximately 2 months with their attending physician.
Invasive dental treatment should be performed in
accordance with the latest guidelines.
Problems inAntithrombotic Therapy
For minor surgery such as tooth extraction, antiplatelet agents and anticoagulants should be continued, and local hemostasis should be maintained.
For surgery with a high risk of bleeding, consult
your family physician and consider suspending
antiplatelet and anticoagulant medications.
Patients taking warfarin have been treated with
heparin as an alternative therapy during the perioperative period, but the Japanese Circulation
Society (JCS)/Japanese Heart Rhythm Society
(JHRS) 2020 Guideline on Pharmacotherapy of
Cardiac Arrhythmias do not recommend preoperative replacement therapy with heparin, based on
the results of the BRIDGE study, however, it is
classied as IIb in the recommended classication, and its efcacy and usefulness have not been
established based on evidence and opinions.
2.7.3 Precautions forImplant
Treatment inPatients
withXerostomia
Although xerostomia is a risk factor for implant
treatment, it is not an absolute contraindication.
Denture treatment is recommended for patients
with xerostomia, but in many cases, dentures
cannot be used because of pain during denture
placement due to mucosal atrophy. Implant treatment should be carried out after thorough evaluation and informed consent, and strict maintenance
is necessary.
The use of steroids, immunosuppressive drugs,
and osteoporosis drugs in patients with collagen
diseases should be carefully considered, bearing
in mind that there is a signicant risk in acquiring
and maintaining osseointegration, as well as a
risk of drug-related osteomyelitis and osteonecrosis of the jaw.
3 Allergic Disease
SatoshiTakada,YuhBaba
3.1 General Discussion
Allergic disease is dened as a condition in which
an excessive immune response to a specic antigen (allergen) is induced to the detriment of the
host. In the past, allergic reactions were classied
into four types [16], but recently, the concept of
type V allergy has been proposed. However, considering the underlying immune response, type V
allergy can be classied as subtype of type II
allergy (Table15.4).
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Table 15.4
Synonym Immediate type
Action
factor
Mechanism
of
occurrence
Major
related
diseases
Examination Specic IgE
Classication of allergic reactions
Type I reaction Type II reaction Type III reaction
Anaphylactic
type
IgE (reagin) IgG, IgM IgG, IgM (immune
When the
antigen binds
again to the IgE
bound to the
mast cell, the
mast cell
releases
chemical
mediators and
symptoms
appear
Anaphylactic
shock
Allergic rhinitis
Bronchial
asthma
Oral allergy
syndrome
Allergy to local
anesthetics
(type I+type
IV)
measurement
Histamine
release test
Challenge test
Cytotoxic type
Cytolysis type
Antibodies bind to
surface antigens of
autologous cells
and damage the
cells
Autoimmune
hemolytic anemia
Immunologic
(idiopathic)
thrombocytopenic
purpura
ABO incompatible
blood transfusion
Coombs test
Antibody
measurement
Immune complex type
Arthus type
complex)
Immune complexes,
which are a
combination of
multiple antigens and
antibodies, are
deposited in tissues,
activating complement
and causing tissue
damage
Serum sickness
Systemic lupus
erythematosus (SLE)
Acute
glomerulonephritis
Complement and
immune complex
assay
Antibody
measurement
Type IV
reaction Type V reaction
Late reaction
type
Cell-mediated
immunity type
Tuberculin type
Sensitized
T-cell
Sensitized
T-cell and
cytotoxic T-cell
react with
antigens,
resulting in
cellular
immune
responses that
damage cells
Granuloma
formation due
to tuberculosis
infection
Tuberculin test
Graft-versushost disease
(GVHD)
Metal allergy
Patch test
Lymphocyte
stimulation test
Cytokine
measurement
Cell function
control type
IgG, IgM
Anti-receptor
antibodies bind to
the receptors of
target cells and
enhance or reduce
the function of the
target cells
Hyperthyroidism
(graves’ disease)
Myasthenia gravis
Antibody
measurement
3.1.1 Type IAllergy
It is also called the immediate type or anaphylactic type because symptoms appear immediately
after the reaction between the causative antigen
(allergen) and IgE antibody. Antigens are taken
up by antigen-presenting cells, which are recognized by Th2 cells, and Th2 cells produce cytokines related to allergic inammation. The
cytokines induce the production of IgE by B
cells, and the IgE antibodies produced adhere to
mast cells, resulting in a sensitized state that is
susceptible to repeated stimulation by the same
antigen. When the antigen binds again to the IgE
bound to the mast cell, various chemical mediators are released from the mast cell, resulting in
increased vascular permeability, smooth muscle
contraction, and increased glandular secretion,
causing symptoms such as angioedema, hypotension, wheezing, dyspnea, and nasal discharge.
Typical diseases include anaphylactic shock,
allergic rhinitis, bronchial asthma, urticaria,
atopic dermatitis, and Latex allergy.
Anaphylactic shock is a condition in which
allergens cause anaphylactic reactions due to
type I allergy, resulting in symptoms such as
hypotension, dyspnea, and loss of consciousness.
It is caused by administration of drugs such as
antimicrobial agents, taking of eggs, wheat, dairy
products, bee venom, contrast media, and
analgesic- antipyretic. In severe cases, loss of
consciousness and death may occur within a few
minutes. In the treatment of anaphylactic shock,
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prompt treatment determines the prognosis, and
adrenaline injection should be given at the same
time as assessment of the airway, respiration, circulation, and consciousness. One type of anaphylaxis caused by occupational allergy is Latex
allergy. This is an immediate allergic reaction to
proteins contained in natural rubber products.
High-risk groups include healthcare workers,
people with a predisposition to atopic dermatitis,
patients who repeatedly undergo medical procedures due to congenital diseases such as spina
bida or chronic diseases, and people with occupations that require frequent use of natural rubber
gloves. Type I allergic diseases related to dentistry include oral allergy syndrome and allergy
to local anesthetics (type I and type IV allergy to
local anesthetics are seen).
damage. The formation of granuloma due to
tuberculosis infection, tuberculin reaction, graft
versus host disease (GVHD), allergic contact
dermatitis, and metal allergy are involved in type
IV allergic reactions.
3.1.5 Type V Allergy
Type V allergy is a subtype of type II allergy in
which anti-receptor antibodies bind to the receptors of target cells, and unlike type II allergy, the
target cells are not destroyed and the anti- receptor
antibodies exhibit ligand-like effects or inhibit
the effects of the ligands. In Graves’ disease
(hyperthyroidism), anti-TSH receptor antibodies
increase thyroid function, while in myasthenia
gravis, anti-acetylcholine receptor antibodies
cause muscle weakness.
3.1.2 Type II Allergy
Type II allergy is caused by the binding of autoantibodies (IgG, IgM) to surface antigens of
autologous cells, resulting in cellular and tissue
damage. The mechanisms include phagocytosis,
cytolysis, and antibody-dependent cell-mediated
cytotoxicity (ADCC). Typical diseases include
autoimmune hemolytic anemia, immunologic
(idiopathic) thrombocytopenic purpura,
Goodpasture’s syndrome (anti-glomerular basement membrane disease), and ABO-incompatible
blood transfusion.
3.1.3 Type III Allergy
Type III allergy is also called immune complex
type or Arthus type. It is a reaction in which
multiple antigens and antibodies are bound
together, and immune complexes are deposited in
tissues, activating complement, resulting in tissue destruction. Typical diseases include serum
sickness, systemic lupus erythematosus (SLE),
hypersensitivity pneumonitis, acute glomerulonephritis, and cryoglobulinemic vasculitis.
3.2 Notes fromDentistry
3.2.1 Allergies Related toDentistry
Oral Allergy Syndrome [17]
It is an immediate type allergy in which swelling
and itch sensation appear in the mucosa of the
oral cavity and pharynx immediately after ingestion of specic foods such as fruits and vegetables. It develops as a cross-reaction to sensitizing
antigens and is often associated with pollinosis.
Symptoms appear within 15min, but the antigenicity of apples, peaches, and pears, which are
easy to become antigens, is easily lost by heating
or digestive enzymes, symptoms are localized to
the oral cavity and pharynx unless taken in large
quantities (Fig. 15.11). The radioallergosorbent
test (RAST), prick test, and scratch test are useful
for diagnosis. The most important treatment is to
avoid antigen without ingesting the causative
food.
Perspective
3.1.4 Type IV Allergy
Unlike type I–III allergies, allergies caused by
T-cell rather than antibodies are called type IV
allergies. Helper T-cell activated by antigens
release a variety of cytokines that activate macrophages and cytotoxic T-cell, resulting in tissue
Allergy toLocal Anesthetics
The incidence of anaphylaxis due to lidocaine
is extremely low, with an incidence of
0.00007%. It is considered to the immediate
allergy if it developed within 1h, and to the
delayed allergy within 72 h. In most cases,
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Fig. 15.11 Oral allergy syndrome. Pruritus and swelling
of the lips are seen after ingestion of melon
however, it causes allergy not to the local anesthetic itself but to the preservative paraben
(paraoxybenzoate) on the antioxidant sodium
sulte. Also other allergic reactions might be
caused by gloves (latex) and disinfectant used
during local anesthesia, and antibacterial, analgesic agents used before and after local anesthesia which must be differentiated. In addition,
vasovagal reexes before local anesthesia,
anomaly of sensation, motor paralysis, discomfort are often thought to be allergic reactions to
local anesthesia. Furthermore, it is necessary to
differentiate from odontophobia, aichmophobia, local anemia due to excessive injection volume, necrosis of the tissue at the insertion
point, and peripheral nerve injury.
Allergy toDental Materials (Metal)
It is delayed type allergy to metals used in dental treatment. About 15 types of metals are used
for it. Titanium (Ti) and vanadium (V) have also
been used due to the spread of dental implant
treatment (Fig.15.12) in recent years. Symptoms
range from systemic to local, including pruritus,
dysgeusia, discomfort in the mouth, and contact
Fig. 15.12 Patch test reagent for metal allergy
dermatitis. These are rarely diagnosed as allergy
to dental metals at the initial examination, and
are often treated symptomatically with unknown
cause, or as climacteric disturbance or xerostomia in some cases. Metal allergies can be diagnosed by testing for metals, and also cements
and resins which are included in dental materials should be tested as well. In addition to the
patch test, a metal lymphocyte stimulation test
(MLST) is also used for diagnosis. The test
should be performed on the back, arms, legs, or
other skin with little hair, and the results are
basically checked at 48 h with checking after
24h, 72h and 1 week as well. Because of the
strong contact, dermatitis or immediate allergic
reaction may rarely occur, symptoms should be
immediately monitored after the test. Treatment
is to change the causative material t
o the appro-
priate therapeutic material.
Stomatitis, oral lichen planus (Fig. 15.13),
palmoplantar pustulosis (Fig.15.14), dermatitis,
erythema, and urticaria are related to dental
materials, and they are in some cases relieved by
metal removal. On the other hand, as in contact
dermatitis, it may cause redness, erosions, papules and bullae within 24h with contact of dental
materials with the oral mucosa (Fig.15.15).
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a
b
c
Fig. 15.13 Lichen planus of the oral cavity. (a, b) White lacy erosions and erythema are seen on both buccal mucosae.
(c) Patch tests showed positive reactions to Au, Ni and Pd
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Fig. 15.14 Palmoplantaris pustulosis. Patch test showed positive reaction to Ni and Pd, and formation of vesicles in
the Ni area
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Fig. 15.15 Allergy to luting cement. Erythema appeared on the buccal mucosa immediately after luting the restoration,
which resolved after removal. A patch test showed large blisters reacting to the luting cement
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References
1. Japan College of Rheumatology. 2020 Japan College
of Rheumatology Clinical Practice Guidelines for
the Management of Rheumatoid Arthrits (Kansetsu
Ryumachi shinryo guideline 2020). Tokyo: Shindan
to Chiryousya; 2020; (in Japanese).
2. Ministry of Health, Labour and Welfare. Committee
on Rheumatism and Other Diseases, Disease Control
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3. Aletaha D, etal. American College of Rheumatology/
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4. Klippel JH, et al., editors. Primer on the rheumatic
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5. The Japanese Society for Temporomandibular Joint
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7. Fukushima M, etal. Primary central nervous system
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8. Obata K, et al. A case of methotrexate-associated
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gingiva: a review of the literature of cases arising in
the oral region in Japan. Jpn J Oral Maxillofac Surg.
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9. Ichiki T, etal. A case of methotrexate-associated lymphoproliferative disorder diagnosed on detection of
ulceration of the gingiva. Jpn J Oral Diag/Oral Med.
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Japanese).
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Polymyositis dermatomyositis subcommittee polymyositis, dermatomyositis treatment guidelines.
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Neurological Diseases
https://t.me/medicina_free
MakikoNishina, TomoakiShintani,
TetsujiOkamoto, KazuhiroMuramatsu,
TadashiKawai, KanakoYamahara, TetsuyaMaeda,
YasuoTerayama, SatoshiOkada,
andTakaakiKamatani
16
1 Dementia andAlzheimer’s
Disease
MakikoNishina
1.1 Denition
Dementia is diagnosed when there is a signicant
decline from the previous level of behavior in one
or more of the following cognitive domains:
complex attention, executive function, learning
and memory, language, perceptual-motor function, and social cognition, which interferes with
daily life [1].
M. Nishina
Department of Internal Medicine, Tokyo Dental
College, Ichikawa General Hospital, Ichikawa, Chiba,
Japan
T. Shintani
Center for Oral Clinical Examination, Hiroshima
University Hospital, Hiroshima, Japan
T. Okamoto
School of Medical Sciences, University of East Asia,
Shimonoseki, Yamaguchi, Japan
K. Muramatsu
Yokohama Tsurumi Rehabilitation Hospital,
Yokohama, Kanagawa, Japan
T. Kawai
Division of Oral and Maxillofacial Surgery,
Department of Reconstructive Oral and Maxillofacial
Surgery, School of Dentistry, Iwate Medical
University, Morioka, Iwate, Japan
1.2 Pathophysiology
It is caused by the loss of neurons and networks in
the central nervous system, which are involved in
cognitive functions. In pathological changes,
degenerative diseases are common and each causative disease has characteristic ndings [2, 3].
1.3 Epidemiology
The prevalence of dementia is on the rise, with a
prevalence of approximately 15% in a 2012 survey. With the aging of the population, it is esti-
K. Yamahara · T. Maeda (*)
Division of Neurology and Gerontology, Department
of Internal Medicine, School of Medicine, Iwate
Medical University, Yahaba, Iwate, Japan
e-mail: maeda@iwate-med.ac.jp
Y. Terayama
Neurological institute, Shonan Keiiku Hospital,
Fujisawa, Kanagawa, Japan
S. Okada
Department of Neurology, Tokyo Dental College,
Ichikawa General Hospital, Ichikawa, Chiba, Japan
T. Kamatani
Department of Oral and Maxillofacial Surgery,
School of Dentistry, Showa University, Ota-ku,
Tokyo, Japan
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023
T. Chiba, H. Yamada (eds.), Internal Medicine for Dental Treatments,
https://doi.org/10.1007/978-981-99-3296-2_16
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mated that the number of dementia patients will
reach 7.3 million by 2025 [4].
1.4 Classication
There is a wide range of diseases that cause
dementia as shown in Table16.1 [5]. Some neurosurgical diseases such as normal pressure
hydrocephalus and chronic subdural hematoma,
Table 16.1 Diseases and conditions that cause major
cognitive impairment (created based on [5])
1. Central
neurodegenerative
diseases
Alzheimer’s disease
Frontotemporal dementia
Lewy body dementia
Huntington’s disease, etc.
2. Vascular dementia 7. Drug-induced
Multi infarct dementia
Chronic subdural
hematoma
Cerebral hemorrhagic
dementia, etc.
3. Normal pressure
hydrocephalus
4. Brain tumor
5. Neurological infections 8. Others
6. Associated with systemic
diseases
Hypothyroidism
Vitamin B
Vitamin B
folic acid deciency
Liver failure
Neurosyphilis, etc.
Psychotropic drug
Sedative drug
Hypnotic
Antidepressant
Analgesics opioids,
NSAIDs, etc.
deciency
1
deciency
12
and some medical diseases such as hypothyroidism and vitamin B12 deciency are treatable
dementia, should be diagnosed and treated as
early as possible.
The most common cause of dementia is
Alzheimer’s disease, which accounts for about
68% of cases, followed by vascular dementia
(19%) and dementia with Lewy body (4.5%) [6].
1.5 Symptoms
We focus on the symptoms of Alzheimer’s disease, which accounts for the majority of cases.
1.5.1 Cognitive Dysfunction
Forgetfulness and memory impairment are characteristic and often the rst symptoms. They forget appointments, misplace objects, and repeat
the same story. The patient is unable to remember
new things, recall them, and use them. A slow
and progressive disorientation, executive function disorder, and visual-spatial impairments
occur as the disease progresses. Many constructive apraxia are also observed, the patient loses
the ability to use daily tools and to imitate by verbal and visual commands, and there is a decrease
in the ability to perform work and housekeeping
(Table16.2) [7]. In daily life, the ability to per-
Table 16.2
Cognitive function Symptoms Examples
Generalized
disorder
Executive
functioning
Memory Forgetfulness Inability to remember new things (anterograde
Language Aphasia
Count Acalculia Trouble handling money and paying bills
Visual-spatial
cognition
Conduct Apraxia (inability to purposely
Social cognitive Disinhibition Inability to recognize the surrounding situation and
Examples of major cognitive dysfunction in dementia (created based on [7])
Generalized attention disorder More mistakes in various tasks
Executive functioning disorder Cannot get things done in a timely manner
Agraphia
Constructive apraxia geographic
disorientation
Visual hallucination/optical illusion
perform some actions)
Blurred and slow to react
amnesia)
Inability to remember what happened before
(retrograde amnesia)
Disorders of speech, comprehension, calling,
recitation, reading, and writing
Dysgraphia
Inability to imitate gures and nger shapes
Get lost in familiar places
Seeing things that are not there
Difculty completing familiar tasks
take appropriate action
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