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17 Neuropsychiatry Diseases
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of communication (communication no Ichijirushii
Shougai notameni Gishichiryou ni Nanjyu shita
Seishinbunretsubyou Kanjya no ichirei). Japanese J
Psychosom Dent. 2000;15:185–9; (In Japanese).
10. Hashimoto K, Matsuda H, etal. The relation between
depressive state in the workplace and subjective symptoms of oral disorders (Shokuba niokeru
Yokuutsujyoutai to Koukuu no Jikakushoujyou). J
Japanese Soc Disability Oral Health. 2014;35:601–7;
(In Japanese).
11. Kaneko Y. Vasoconstrictor (with local anesthetic) and its usage (Kekkan Shushukuyaku
(Kyokushomasuiyaku Tenka) to Sono Tsukaikata).
J Japan Dent Assoc. 1996;48(12):1282–96; (In
Japanese).
12. Ichinohe T, Shimada M. A questionnaire survey
regarding the administration of lidocaine hydrochloride solution containing adrenaline for dental use in
regular users of antipsychotics. J Japanese Dent Soc
Anesthesiol. 2014;42(2):190–5; (In Japanese).
13. Toru M, Nakane Y, Komiyama M (translation supervisor). ICD-10 mental and behavioral disorders: clinical description and diagnostic guidelines. revised ed.
Tokyo; Igaku Shoin. 2005; (In Japanese).
14. Japanese Medical Society of Alcohol and Addiction
Studies/The Japanese Society of Alcohol-Related
Problems eds. Guide to diagnosis and treatment
of alcoholism based on the new guidelines for the
diagnosis and treatment of alcohol and drug use
disorders. 1st ed. Kyoto; Japanese Medical Society
of Alcohol and Addiction Studies/Yokosuka; The
Japanese Society of Alcohol-Related Problems. 2018.
(In Japanese).
uploads/pdf/Guide- for- diagnosis- and- treatment- ofalcoholism201907.pdf.
15. Khairnar MR, Wadgave U, Khairnar SM. Effect of
alcoholism on oral health: a review. J Alcohol Drug
Depend. 2017;5(3):266.
16. Wikipedia. Meth mouth. https://en.wikipedia.org/
wiki/Meth_mouth.
https://www.jmsaas.or.jp/wp- content/
Infectious Diseases
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YukiYamada, AkiraSuwabe, ToshihiroIto,
andSatoshiGoto
18
1 Microbial Substitution
YukiYamada,AkiraSuwabe
1.1 Disease Overview
andPathophysiology
Microorganisms (mostly bacteria, but also fungi,
viruses, etc.) inhabit on all surfaces of the human
body and in contact with the outside world. These
microorganisms are called indigenous microbiota,
and bacteria in particular are called indigenous bacterial ora or normal bacterial ora. Bacterial ora in
humans exists in the skin, eyes, nasopharynx, gastrointestinal tract from the oral cavity to the anus, and
urinary and reproductive organs, and the kinds of
bacteria present in these areas vary greatly depending on site, age, gender, race, diet, and lifestyle.
Yuki Yamada was deceased at the time of publication.
Y. Yamada · A. Suwabe
Department of Laboratory Medicine, Iwate Medical
University Schoolof Medicine, Yahaba, Iwate, Japan
T. Ito (*)
Department of Infectious Diseases, National Hospital
Organization Sendai Medical Center, Sendai, Miyagi,
Japan
e-mail: ito.toshihiro.zw@mail.hosp.go.jp
S. Goto
Department of Oral and Maxillofacial Surgery,
National Hospital Organization Sendai Medical
Center, Sendai, Miyagi, Japan
Microbial substitution is a phenomenon in
which the normal bacterial ora is disturbed by the
abnormal growth of bacteria that normally do not
exist or exist only in small numbers due to a
decrease in the normal ora. When a broadspectrum antimicrobial agent is administered, not
only the target bacteria but also sensitive strain in
the normal ora is reduced. As a result, nonsensitive or resistant bacteria multiply abnormally.
The causative microorganisms include fungi such
as Candida spp., Pseudomonas aeruginosa, Gram-
negative rods such as Serratia spp., and anaerobic
bacteria. Clinical manifestations of microbial substitution include oral candidiasis in the oral ora
and antimicrobial-associated diarrhea and pseudomembranous enteritis caused by Clostridioides
difcile infection (CDI) in the intestinal ora. In
this section, CDI is mainly described.
1.2 Epidemiology
C. difcile is a spore-forming, obligatory anaerobe,
gram-positive bacillus, and is widely present in the
environment. Asymptomatic carriers are found in
5–10% of healthy adults and 15–70% of newborns.
Risk factors for the development of CDI are disruption of the intestinal microbiota (e.g., administration of antimicrobial agents and antacids), exposure
to C. difcile (e.g., prolonged hospitalization), and
host factors (e.g., advanced age, serious underlying
disease, chemotherapy, tube feeding, laparotomy).
© 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_18
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CDI is the most frequently associated with healthcare-associated diarrhea in adults [1].
1.3 Symptoms
The main symptoms of CDI are diarrhea, abdominal pain, and fever. Severe cases suffer from pseudomembranous enteritis, toxic megacolon, paralytic
ileus, and gastrointestinal perforation. These occur
after exposure to incentive drug (antibacterial drug)
for a few days to 2 weeks. The pathogenic factors of
CDI are toxin A (enterotoxin) and toxin B (cytotoxin), produced by C. difcile, which damage the
intestinal tract and cause diarrhea and enteritis.
Recently, a third toxin, binary toxin, has attracted
attention and has been reported to be associated
with severe disease as a highly pathogenic strain.
PCR ribotype 027 (BI/NAP1/027), a representative
strain that produces this toxin, has been spreading in
North America and Europe since the 2000s. This
strain has not been spreading in Japan, even though
a few cases have been reported [2, 3].
1.4 Clinical Examination
andDiagnosis
CDI is caused by toxins (toxin A and toxin B)
produced by C. difcile and is diagnosed by conrmation of these toxins. To improve the detection rate, immunochromatographic antigen
detection kits that simultaneously detect the glutamate dehydrogenase (GDH) antigen of all C.
difcile are used. Nucleic acid amplication technique can determine the presence of toxin with
high sensitivity. In addition, colonoscopy is performed to check for the presence of pseudomembranes, which are characteristic of the disease.
Because asymptomatic carriers with toxinproducing strains exist in healthy adults, detection
of toxin per se in a human without diarrhea is of
little clinical signicance. The presence of clinical
symptoms is important for the diagnosis of
CDI.Japanese guidelines state that testing should
be performed only when diarrheal symptoms are
present [4]. Furthermore, because asymptomatic
carrier of C. difcile is common in children, testing
should not be performed, and the guidelines do not
dene CDI in children younger than 2years [4, 5].
1.5 Treatment andInfection
Control
The treatment of CDI is to discontinue the causative drug as much as possible. Even if the patient
is positive for CD toxin test, treatment is not
required if the patient does not have diarrhea.
Japanese guidelines [4] recommend metronidazole and vancomycin for non-severe cases and
daxomicin for severe and recurrent cases as
antibacterial agents against C. difcile.
Bezlotoxumab (anti-toxin B antibody) as a
relapsing preventer and probiotics as a prophylactic agent are available.
CDI requires contact infection prevention
measures. It is known that C. difcile spores
spread to the hospital environment by adhering
to the hands of healthcare workers and caregivers. Because C. difcile spores are resistant to
heat and desiccation and are very stable in the
environment, they can survive for long periods
of time. Furthermore, alcohol disinfection is
ineffective, so items suspected of being contaminated should be disinfected with sodium hypochlorite. Medical staff should wear gloves and
disposable gowns when in contact with patients
and wash their hands with running water and
soap.
1.6 Recent Findings
As many as 100 trillion bacteria are present in the
human intestinal tract. Metagenomic analysis of
the intestinal microbiota has identied intestinal
bacteria associated with various constitutions and
diseases by detecting the proportion of the ora
and specic bacteria.
2 AIDS (Acquired
Immunodeciency
Syndrome)
ToshihiroIto
2.1 Introduction
Acquired Immunodeciency Syndrome (AIDS)
was rst reported in June 1981 as an outbreak of
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pneumocystis pneumonia among the gay (male
homosexuals) in Los Angeles. Two years later, it
was found to be caused by a viral infection. This
tion and prejudice against this disease that arose
in the early 1980s has not been eradicated even
now, and stigma still swirls around.
is human immunodeciency virus (HIV) infection. Until the discovery of antiretroviral therapy
(ART) in the mid-1990s, this infection meant
2.2 Disease Overview
death, and the route of transmission (sexual intercourse, blood transfusion/needlestick, mother-tochild) and the special characteristics of the
infected group led the world to panic. Since the
start of ART, by the development of drugs and
treatment methods, the lifespan has been similar
to that of uninfected people. Now, we can con-
HIV infection is dened as the presence of HIV
in the body (or more precisely, the presence of
HIV in the host DNA as a provirus), and AIDS is
dened as the development of some index disease associated with immunodeciency (23 types
in Japan: Table18.1 [6, 7]).
sider HIV infection is chronic disease. The most
important things for the control of this infection
are to know the existence of this virus in the body
2.3 Pathophysiology
and to start ART as soon as possible, and to ght
against discrimination and prejudice against
HIV-infected people based on social customs and
systems, and stigma. Unfortunately, discrimina-
Table 18.1 AIDS indicator diseases (created based on [6])
A.Mycosis 1. Candidiasis (esophagus, trachea, bronchus, lung)
B.Protozoan
infection
C.Bacterial
infections
D.Viral
infections
E.Tumor 16. Kaposi’s sarcoma
F.Others 20. Recurrent pneumonia
a
(a) Disseminated throughout the body; (b) Occurred in a site other than the lung, neck, or hilar lymph nodes
b
Those under 13years of age who have had two or more of the following multiple or recurrent events within 2 years due
to pyogenic bacteria such as Hemophilus, Streptococcus, etc. (a) septicemia, (b) pneumonia, (c) meningitis, (d) osteoarthritis, (e) abscesses in sites other than the middle ear or cutaneous mucosa, or in deep organs
c
For pulmonary tuberculosis among C11 active tuberculosis and E19 invasive cervical cancer, only when symptoms or
ndings suggestive of HIV-induced immunodeciency are observed
d
(a) Ulceration of the mucous membrane or skin persisting for more than 1 month (b) Bronchitis, pneumonia, and
esophagitis after 1month of age
2. Cryptococcosis (other than lung)
3. Coccidioidomycosis
4. Histoplasmosis
5. Pneumocystis pneumonia
6. Toxoplasmic encephalopathy (after 1month of age)
7. Cryptosporidiosis (with diarrhea lasting more than 1 month)
8. Isosporiasis (with diarrhea lasting more than 1month)
9. Pyogenic bacterial infection
10. Salmonella bacteremia (recurrent, excluding those caused by typhoid bacilli)
11. Active tuberculosis (pulmonary tuberculosis or extrapulmonary tuberculosis)
12. Nontuberculous mycobacterial infection
13. Cytomegalovirus infection (after 1month of age, except liver, spleen, and lymph nodes)
14. Herpes simplex virus infection
15. Progressive multifocal leukoencephalopathy
17. Primary cerebral lymphoma
18. Non-Hodgkin lymphoma (a) large cell, immunoblastic type; (b) Burkitt type)
19. Invasive cervical cancer
21. Lymphocytic interstitial pneumonia/pulmonary lymphoid hyperplasia: LIP/PLH complex
(<13years)
22. HIV encephalopathy (dementia or subacute encephalitis)
23. HIV exhaustion syndrome (general prostration or slim disease)
a
a
b
d
c
HIV infection is mainly characterized by immunodeciency caused by HIV-induced decrease in
CD4-positive cells, and if not properly diagnosed
a, c
a
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Y. Yamada et al.
and treated, AIDS develops and death occurs in
about 10 years.
HIV present in the body uids of an infected
person is transmitted through only three routes.
They are (1) sexual intercourse (homosexual/heterosexual); (2) blood transfusion/needle stick
(medical accident, sharing of injection devices
such as stimulants injections, etc.); and (3)
mother-to-child (transplacenta, vaginal, lactation). HIV belongs to the retrovirus family of
RNA viruses, and its most distinctive feature is
its ability to convert RNA to DNA using its own
reverse transcriptase enzyme, and to incorporate
it into the host cell’s DNA using an integrase.
CD4 is the receptor of HIV, and CD4-positive
cells (CD4-positive lymphocytes and macrophages), which play a central role in the human
immune system, are the target of HIV.As long as
the infected cells remain alive, HIV is reproduced
and the infected cells are eventually destroyed. A
erce battle between CD4-positive cells and HIV
is repeated invivo, resulting in the host’s defeat,
which leads to immunodeciency and the development of AIDS.The disease is classied into
three phases: acute phase, asymptomatic carrier,
and AIDS phase.
2.4 Epidemiology
According to the UNAIDS report of 2020 [8],
there are about 38 million people living with
HIV in the world, two-thirds of whom are in
sub- Saharan Africa, and there is little gender
difference. It is said that drug users who inject
stimulants, gay, commercial sex workers and
their partners, transgenders, are a group with a
high risk of infection. In Africa, however, more
than half of the people living with HIV are
infected by male-to-female, mother-to-child
transmission than by these high-risk groups.
The annual number of new infections is 1.7 million and the number of AIDS-related deaths is
690,000, both of which are on a downward trend
due to the spread of ART implementation. In
Japan, the total number of new infections was
31,385 at the end of 2019 (excluding victims of
blood products), and the annual number of new
reports was 1,236 (333 for AIDS), showing a
decreasing trend. MSM (men who have sex with
men) and heterosexual contact infections
accounted for 67.2% and 15.5%, respectively
[9].
2.5 Symptoms andDiagnosis
There are no specic clinical symptoms of HIV
infection. Symptoms appear in the early phase of
infection (acute phase) and during the AIDS
phase, and the asymptomatic carrier (AC) phase,
which accounts for most of the natural course of
the disease, follows a course similar to that of
uninfected persons. The acute phase is said to
resemble infectious mononucleosis, and it is no
different from general viral infections, and subclinical infections are also possible. Since the
symptoms of AIDS are also due to complications,
HIV diagnosis is impossible unless HIV-related
blood examination is performed considering the
possibility of HIV infection. Screening tests have
a certain percentage of false-positives, and denitive diagnosis is made by blood-based HIV antibody conrmation test (WB or
immunochromatography:IC method) or detection of HIV-RNA by PCR method [7]. In the
acute phase of the disease, the WB or IC method
may produce false negatives, so the PCR method
should be used in combination with the WB or IC
method, and retesting after a period of time is
necessary.
2.6 Classication
There are two types, HIV-1 and HIV-2, and it is
said that in the beginning of the twentieth century
(around 1920), Simian immunodeciency virus
(SIV) that had infected primates in Africa
mutated and caused human-to-human infection
(HIV) [10]. The former (HIV-1) originated in
chimpanzees and the latter (HIV-2) in gorillas
and orangutans, and HIV-1 is widespread in
humans, while HIV-2 is very rare.
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2.7 Infection Control
Condoms are effective in preventing sexually
transmitted infections, including HIV. However,
the difculty of prevention by condoms has been
shown by their histories. About HIV, the current
prevention method is to suppress HIV in the
blood below the detection limit by ART: treatment as prevention (TasP). It has been conrmed
that infected people who have been successfully
treated are not sexually transmitted (undetectable
equals untransmittable: U=U) [11, 12]. Infection
can be prevented by taking anti-HIV drugs even
for medical contamination accidents (Postexposure prophylaxis: PEP) [13]. Although not
yet common in Japan, pre-exposure prophylaxis
(PrEP) [14], in which anti-HIV medication is
taken before sexual intercourse, is effective as a
preventive measure for non-infected persons during sexual procedure.
2.8 Treatment
The therapeutic philosophy is to promote the
recovery of CD4 positive cells and restore the
immune system by reducing the HIV present in
the body to below the detection limit. Once HIV
infection is diagnosed, ART should be initiated as
soon as possible.
Drugs used in ART are classied by mechanism of action into nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse
transcriptase inhibitors (NNRTIs), protease
inhibitors (PIs), integrase inhibitors (INSTIs),
and entry inhibitors, which are categorized as key
drugs (more potent in suppressing HIV) and
backbone drugs (complementary to key drugs
and enhancing viral suppression). In Japan, there
are 37 types of drugs as of March 2020 (including different formulations and xed-dose combinations). Currently, ART is generally performed
with a combination of two NRTIs as the backbone and one key drug. Specic drug selection is
based on antiviral effects, side effects, and adherence to medications, Since guidelines for HIV
managements are frequently updated annually in
the eld of intense new drug development, the
introduction of ART should be asked of a specialist with medical experience. The most recommended combinations for initial treatment are
listed in the table (Fig.18.1) [6].
2.9 Prognosis
If ART is successful, the prognosis is good. Life
expectancy is similar to that of uninfected persons. However, if treatment fails for any reason,
the patient will have a desperate course as in the
previous ART era.
2.10 Recent Findings
Recent ndings are as follows:
1. Aiming for prevention of infection (TasP,
PrEP, and PEP), early diagnosis, and early
treatment.
2. Continued development of drugs that take
into account adherence to medication and
reduction of side effects.
3. Control and eradication of the spread of infection have become the main focus.
4. Countermeasures against aging and associated complications (lifestyle-related diseases
and malignant tumors) due to improved prognosis are future problems.
2.11 Conclusion
Oral lesions are very important in the diagnosis
of immunodeciency diseases, and dentists play
an important role in the early diagnosis of HIV
infection.
334
BIC: Bictegravi
3TC: lamivudine, RAL: Raltegravir, DRV: Darunavir, cobi: Cobicistat, rtv: Ritonavir, RPV: Rilpivirine
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Y. Yamada et al.
Combination Number of
medications
BIC/TAF/FTC 1 Unlimited 1
DTG/ABC/3TC 1 Unlimited 1
DTG + TAF/FTC 1 Unlimited 2 (HT)
RAL (600 mg tablet) + TAF/FTC 1 Unlimited 3
RAL (400 mg tablet) + TAF/FTC 2 Unlimited 3
DRV/cobi/TAF/FTC 1 During and immediately after a
DRV + rtv + TAF/FTC 1 During and immediately after a
Timing of medication Number of
tablets per
day
1
meal
3
meal
Tablets to be
taken in a
day [CH1]
(HT)
(HT)
(LT)
RPV/TAF/FTC 1 During and immediately after a
meal
r, TAF: Tenofovir alafenamide, FTC: emtricitabine, DTG: Dolutegravir, ABC: Abacavir
Fig. 18.1 Most recommended combinations for initial ART (created based on [6])
2.12 Notes fromDentistry
Perspective
performed when patients have AIDS onset.
However, because it takes several years from HIV
infection to the onset of AIDS, patients may visit
SatoshiGoto
a dentist without being aware of their infection. In
addition, about 30% of the cases, the infection is
2.12.1 Dental Treatment ofPatients
withAIDS (HIV Infection)
Since AIDS (acquired immune deciency syndrome) is a condition in which HIV-infected
patients have symptoms caused by immunodeciency, it is very rare that dental treatment must be
known only after the onset of AIDS, and in some
cases, oral symptoms lead to the diagnosis of
AIDS.Therefore, it is important to understand the
main characteristics of oral symptoms caused by
the onset of AIDS and to refer patients to specialized medical institutions. Although there are no
1
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Fig. 18.2 Oral candidiasis
Fig. 18.3 Gingival Kaposi’s sarcoma. (Courtesy of Dr.
Yutaka Maruoka, Center Hospital of the National Center
for Global Health and Medicine)
diseases specic to the oral cavity in the list of
index diseases by the Committee on AIDS Trends
of the Ministry of Health, Labour and Welfare,
Japan [15], the main oral symptoms include oral
candidiasis (Fig. 18.2), Kaposi’s sarcoma
(Fig. 18.3), lymphoma (Fig. 18.4), and severe
marginal periodontitis.
335
Fig. 18.4 Malignant lymphoma of the palate. (Courtesy
of Dr. Yutaka Maruoka, Center Hospital of the National
Center for Global Health and Medicine)
2.12.2 Precautions forDental
Treatment
Because of the progress of therapeutic drugs, the
viral load of HIV infection can be controlled even
after the onset of AIDS, and long-term survival
can be expected, the aging of the population and
nursing care have become problems. In Japan,
the majority of patients are treated at a specialized department. The response rate of therapeutic
drugs is high, and the amount of virus in the
blood of most patients is said to be below the
detection limit if they take the drugs properly.
Therefore, dental treatment of patients with controlled disease can be performed in the same
manner as that of normal patients, including surgical procedures such as tooth extraction. Dentists
should communicate with their primary care physician and receive information on viral load and
CD4 levels before undergoing dental treatment.
On the other hand, patients with HIV infection
may come for dental treatment with a high viral
load without being aware of it, so it is important
to provide treatment in accordance with standard
precautions.
Interactions between HIV medications and other
drugs are often a problem in the medical care of
HIV-infected patients. The use of antibacterial
agents and analgesics frequently used in dentistry
does not pose a problem, but the interaction
should be checked when sedation is used. In
addition, the majority of HIV infections in Japan
are sexually transmitted, and it should be kept in
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Y. Yamada et al.
mind patients may have a coinfection with other
sexually transmitted diseases or viral infections.
On the other hand, patients with drug- induced
HIV infection have a tendency to bleed because
of hemophilia in the background, so it is necessary to communicate with the attending physician if bleeding treatment is necessary.
References
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3. Knight DR, et al. Diversity and evolution in the
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4. Kunishima H, et al. The Japanese clinical practice guidelines for management of Clostridioides
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unaids.org/sites/default/files/media_asset/
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Labour and Welfare: 2019 Annual Report on AIDS
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Pregnancy andBreastfeeding
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RieOyama andTetsuroIkebe
19
1 Pregnancy andLactation
RieOyama
1.1 Establishment ofPregnancy
1.1.1 Pregnancy
Pregnancy occurs when an egg and a sperm fertilize and that implant into the utrine endometrium
lining asn fetrilized egg. Understanding gametogenesis, fertilization, and embryo implantation
leads to the understanding of normal and abnormal maternal changes, fetal development, and
placentation in pregnancy [1].
1.2 Physiology ofPregnancy
Healthy pregnant women have signicant physiological changes during pregnancy. Weight gain is
approximately 8 to 10kg during pregnancy due to
an increase in the gestational uterus, breasts, and
circulating blood volume (or plasma volume),
Many changes might almost normalize to their
pre-pregnancy state by the end of pregnancy [2].
R. Oyama (*)
Department of Obstetrics & Gynecology, Iwate
Medical University, Yahaba, Iwate, Japan
e-mail: rieoyama@iwate-med.ac.jp
T. Ikebe
Department of Oral and Maxillofacial Surgery,
Fukuoka Dental College, Fukuoka, Japan
1.2.1 Material Metabolism
• Maternal insulin resistance begins in the sec-
ond trimester and peaks in the third trimester.
• There is an increase in total cholesterol and
triglyceride levels in pregnancy.
• A pregnant woman requires an increased
intake of protein during pregnancy.
1.2.2 Changes intheCardiovascular
System
The resting heart rate increases by about 10 beats
per minute. The diaphragm is elevated, the heart
is displaced upward to the left, the apex is displaced outward to the left, and shows an enlarged
heart on a chest X-ray.
1.2.3 Circulating Blood Volume
At the end of pregnancy, the mean circulating
blood volume increases by 40–50% of the nonpregnant level and normalizes to the non- pregnant
level within 4–6weeks after delivery.
1.2.4 Blood Pressure
Peripheral vascular resistance decreases under
the inuence of progesterone, as the smooth
muscle of the blood vessels relaxes and the vessels dilate. As a result, blood pressure remains
constant or decreases slightly. In the lower
extremities, the gestational uterus compresses
the pelvic veins and inferior vena cava, resulting
in edema of the lower extremities, varicose
veins in the lower extremities and vulva, and
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023
T. Chiba, H. Yamada (eds.), Internal Medicine for Dental Treatments,
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