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Table 14.5
1. Precursor lymphoid tumor
2. Mature B-cell neoplasms
• Diffuse large B-cell lymphoma
• Follicular lymphoma
• Mucosa-associated lymphoid tissue lymphoma
• Mantle cell lymphoma
• Burkitt lymphoma
• Intravascular large B-cell lymphoma, etc.
3. Mature T- and NK-cell neoplasms
• Adult T-cell leukemia/lymphoma
• Extranodal NK/T-cell lymphoma, nasal type
• Peripheral T-cell lymphoma
• Undifferentiated large cell lymphoma, etc.
4. Hodgkin lymphoma
• Nodular lymphocyte-predominant Hodgkin
• Classical Hodgkin lymphoma
5. Post-transplant lymphoproliferative disorders
6. Histiocytic and dendritic cell neoplasms
Classication of lymphoid neoplasms
lymphoma
clinical picture. In the fourth edition (WHO-
2017), revised in 2017, the number of classication items for lymphoid tumors is 112 [14]. Since
it is not possible to show all of them in this paper,
a rough classication is given (Table14.5).
4.5 Symptoms
Malignant lymphoma can involve any part of the
body. Lymphadenopathy is the main symptom,
but organ-specic symptoms (abdominal distention due to hepatosplenomegaly, dyspnea due to
pleural effusion, diarrhea and intestinal obstruction due to gastrointestinal tract involvement)
may occur if extralymphatic organs are involved.
Fever, sweating, and weight loss (symptom B)
may be observed as systemic symptoms.
4.6 Clinical Examination
The examination of malignant lymphoma can be
divided into two main categories: denitive
diagnosis and staging. Denitive diagnosis is
based on histopathological diagnosis using
tumors obtained by surgical resection or biopsy
of lymph nodes. Once a denitive diagnosis is
made, staging is performed to determine the
treatment strategy. Imaging tests such as CT
scan and PET-CT scan, bone marrow examination, and cerebrospinal uid examination are
used for staging.
4.7 Treatment
Chemotherapy and radiation therapy are the
mainstay of treatment for malignant lymphoma.
The treatment strategy is determined based on the
patient’s general condition, histopathological
diagnosis, grade, and clinical stage. Stages are
classied as stages I–IV, as shown in Table14.6,
with stages I and II being the localized stages and
stages III and IV being the advanced stages.
In the localized stage, radiation therapy may
be added after chemotherapy. In the advanced
stage, chemotherapy is the mainstay. Since chemotherapy depends on the type and grade of the
disease, this article discusses representative
lymphomas.
4.7.1 Hodgkin’s Lymphoma
Doxorubicin, bleomycin, vinblastine, and dacarbazine combination therapy (ABVD therapy) is
the initial standard of care. Recently, the combination of brentuximab vedotin (BV), an anti CD30 monoclonal antibody conjugated with the
anticancer agent monomethyl auristatin E, and
doxorubicin, vinblastine, and dacarbazine has
been covered by insurance in Japan and has
been positioned the standard of care. The combination of BV, high-dose chemotherapy with
autologous transplantation, and immune check-
Table 14.6
Stage IOne lymph node region or one extranodal
Stage IILesions in two or more lymph node areas that
Stage
III
Stage IVDiffuse and disseminated lesions of extranodal
Stages of lymphoma
lesion
are conned to either the upper or lower part of
the diaphragm, or one extranodal lesion and a
lesion in the lymph node region on the
ipsilateral side of the diaphragm
Multiple lymph node areas on both sides of the
diaphragm or extranodal lesions
tissue
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H. Sawai et al.
point inhibitors such as nivolumab and pembrolizumab is used for patients with refractory
disease.
4.7.2 Diuse Large B-Cell Lymphoma
For DLBCL, the most common form of the disease, the standard of care is R-CHOP therapy, a
combination of rituximab, an anti-CD20 monoclonal antibody, and cyclophosphamide, doxorubicin, vincristine, and prednisolone.
4.7.3 Follicular Lymphoma
Follicular lymphoma, the second most common
type of lymphoma, is a low-grade lymphoma
that progresses on a yearly basis. It progresses
slowly and often without subjective symptoms,
but is difcult to cure. After evaluating the
stage, tumor volume, and course of the disease,
the following options should be selected for
each patient: (1) careful observation, (2) rituximab monotherapy, or (3) rituximab combination chemotherapy.
4.7.4 Extranodal NK/T-Cell
Lymphoma, Nasal Type
Most of them are rare lymphomas derived from
NK cells. About 70% of patients have localized
stage disease, mainly in the nasal cavity or surrounding tissues. Because of the low efcacy of
CHOP therapy even in the localized stage,
chemoradiation with concurrent radiotherapy
and chemotherapy (2/3 dose of DeVIC; dexamethasone, etoposide, ifosfamide, and carboplatin) is recommended [15].
4.9 Recent Findings
As the molecular pathogenesis has been claried, classication of diseases based on genetic
abnormalities has progressed; in DLBCL, the
classication of germinal center B-cell type
and activated B-cell type was proposed using
DNA microarray [17]. For follicular lymphoma,
a prognostic index (m7-FLIPI) incorporating
the seven gene mutation states of EZH2,
ARID1A, MEF2B, EP300, FOXO1, CREBBP,
and CARD11 has been proposed, and prognostic stratication has been performed [18]. It is
expected that novel therapies for the poor prognosis group will be developed in the future.
4.10 Notes fromDentistry
Perspective [5, 19, 20]
DaishiSaito
4.10.1 Malignant Lymphoma Arising
intheOral Cavity
Between 2001 and 2014, diffuse large B-cell lymphoma accounted for about 40% of reported cases
of ML in the oral cavity in Japan, followed by
MALT lymphoma (about 30%), extranodal NK/Tcell lymphoma, and Burkitt lymphoma. The palate, maxillary gingiva (Fig.14.9), and mandibular
4.8 Prognosis
Prognosis varies according to clinical stage and
disease type; in DLBCL, age (≥61years), LDH
(>normal), performance status (≥2), stage (stage
III–IV), and extranodal disease (≥2 sites) are
prognostic factors, and the 4-year survival rate is
94% for 0 factors, 79% for 1 or 2 factors, and
55% for 3 or more factors [16].
Fig. 14.9 Malignant lymphoma of maxillary gingiva
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Fig. 14.10 Oral candidiasis. White pseudomembranes
are seen on the tongue and buccal mucosa
gingiva are the most common initial sites in the
oral cavity (20% each), followed by the mandible
and buccal mucosa. Intraoral ndings included
masses or swellings in about 70% of cases and
ulcers or necrosis in about 20% of cases [20].
4.10.2 Treatment
Histopathological examination by biopsy is
essential for the denitive diagnosis of ML, and
ML may be detected by biopsy of intraoral
lesions. When ML is suspected by histopathological ndings, immediate consultation with a
specialist is necessary. Drug therapy (chemotherapy, molecular targeted therapy), radiotherapy, and hematopoietic stem cell transplantation
are available for the treatment of ML, and side
effects such as stomatitis and other oral mucosal
problems are common during any of these treatments. In addition, since the source of infection
in the oral cavity may lead to serious infections
such as bacteremia and sepsis due to immunosuppression during treatment, it is necessary to
collaborate with the attending physician and to
conduct thorough oral screening before treatment and oral care during treatment (Fig.14.10).
References
1. Yazaki Y, editor. ASAKURA internal medicine.
(Naikagaku). 11th ed. Tokyo, Asakura Shoten; 2019.
(in Japanese).
2. Nishida J, et al., editors. Internal medicine for the
odontology. (Shika no tame no Naikagaku). Revised
4th ed. Tokyo: Nankodo; 2018. (in Japanese).
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3. Shirasuna K, Kogo M, editors. Oral surgery. (Kouku
Gekagaku). 3rd ed. Tokyo: Ishiyaku Shuppan; 2010.
(in Japanese).
4. Kizaki M, Tamaru J, editors. Pathogenesis of leukemia
and lymphoid tumors according to the revised fourth
edition of the WHO classication. (WHO Bunrui
Kaitei Dai 4 han niyoru Hakketsubyo Lympakei
Shuyou no Byoutaigaku). Tokyo: Chugai Igaku-sha;
2019. (in Japanese).
5. The Japanese Society of Hematology, editor. Practical
guidelines for hematological malignances, 2018,
revised version (Zouketsuki Shuyou Shinryou guideline). 2018 ed. Tokyo: Kanehara Shuppan; 2018. (in
Japanese).
6. Shima M.Chapter XI: thrombotic and hemostatic diseases, 8. Hemophilia. (Dai XI Shou: Kessen Shiketsu
Shikkan, 8. Ketsuyubyo). In: Japanese Society
of Hematology, editor. Textbook of hematology
(Ketsueki Senmon-I text). Revised 2nd ed. Tokyo:
Nanko-do; 2015. p.396–400. (in Japanese).
7. Ieko M. 13. Symptoms of lymphatic and vascular
disease, 2. Petechiae, purpura. Internal medicine diseases diagnosed from symptoms. (13. Lympa Kekkan
no Shoujyou, 2. Tenjyou Shukketsu, Shihan). In:
Watanabe J, Sawada K, editors. Internal medicine
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miru Naika Shikkan). Tokyo: Medical View; 2005.
p.404–8. (in Japanese).
8. The Japanese Society on Thrombosis and Hemostasis.
Guideline for the treatment of haemostasis in patients
with haemophilia without inhibitors (Inhibitor nonai
Ketsuyubyo Kanjya nitaisuru Shiketsu Chiryo guideline). In: Hemostatic therapy guideline for patients
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Hemostasis; 2013. p.1–24. (in Japanese). https://www.
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inhibitor_H1_B.pdf.
9. Horn H, etal. MYC status in concert with BCL2 and
BCL6 expression predicts outcome in diffuse large
B-cell lymphoma. Blood. 2013;121:2253–63.
10. National Cancer Center Japan Information Service.
Latest cancer statistics. (in Japanese). https://ganjoho.
jp/reg_stat/statistics/stat/summary.html.
11. Morton LM, et al. Rationale and design of the
International Lymphoma Epidemiology Consortium
(InterLymph) non-Hodgkin lymphoma subtypes project. J Natl Cancer Inst Monogr. 2014;48:1–14.
12. Morton LM, et al. Etiologic heterogeneity among
non-Hodgkin lymphoma subtypes: the InterLymph
non-Hodgkin lymphoma subtypes project. J Natl
Cancer Inst Monogr. 2014;48:130–44.
13. Swerdlow SH, etal. WHO classication of tumours
of haematopoietic and lymphoid tissues. 4th ed. Lyon:
IARC Press; 2008.
14. Swerdlow SH, etal. WHO classication of tumours of
haematopoietic and lymphoid tissues. Revised 4th ed.
Lyon: IARC Press; 2017.
15. Yamaguchi M, et al. Phase I/II study of concurrent
chemoradiotherapy for localized nasal natural killer/
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T-cell lymphoma: Japan Clinical Oncology Group
Study JCOG0211. J Clin Oncol. 2009;27:5594–600.
16. Sehn LH, etal. The revised International Prognostic
Index (R-IPI) is a better predictor of outcome than
the standard IPI for patients with diffuse large
B-cell lymphoma treated with R-CHOP. Blood.
2007;109:1857–61.
17. Alizadeh AA, et al. Distinct type of diffuse large
B-cell lymphoma identied by gene expression proling. Nature. 2010;403:503–11.
18. Pastore A, et al. Integration of gene mutations in
risk prognostication for patients receiving rst-line
immunochemotherapy for follicular lymphoma: a
retrospective analysis of a prospective clinical trial
and validation in a population-based registry. Lancet
Oncol. 2015;16:1111–22.
19. National Cancer Center Japan. Cancer information
service. (in Japanese). https://ganjoho.jp/reg_stat/
index.html.
20. Kawamata A, etal. A clinical study of malignant lymphomas arising in the oral and maxillofacial region
with a review of case reports in Japan. Oral Oncol.
2015;27:119–25. (in Japanese).
Immune System Diseases
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YoshihiroMatsukawa, NatsumiIkumi,
YoshikiHamada, NoriyukiSeta, KeikoAota,
MasayukiAzuma, YuhBaba, andSatoshiTakada
15
1 Rheumatoid Arthritis [1–4]
YoshihiroMatsukawa, NatsumiIkumi
1.1 What Is Rheumatoid Arthritis
(RA)?
Rheumatoid arthritis (RA) is a chronic inammatory disease caused by an autoimmune mechanism
Y. Matsukawa
Department of Internal Medicine, Tsurumi University
Dental Hospital, Yokohama, Kanagawa, Japan
N. Ikumi
Division of Cutaneous Science, Department of
Dermatology, Nihon University School of Medicine,
Itabashi-ku, Tokyo, Japan
Y. Hamada
Department of Oral & Maxillofacial Surgery, School
of Dental Medicine, Tsurumi University, Kanagawa,
Yokohama, Japan
N. Seta (*)
Department of Internal Medicine, Tokyo Dental
College, Ichikawa General Hospital, Ichikawa, Chiba,
Japan
e-mail: nseta@tdc.ac.jp
K. Aota · M. Azuma
Graduate School of Biomedical Sciences, Tokushima
University, Tokushima, Japan
Y. Baba · S. Takada
Department of General Clinical Medicine, Ohu
University School of Dentistry, Koriyama,
Fukushima, Japan
in which joints become the target of immune
responses. It is a chronic inammatory disease
involving mainly in the synovium and other joint
components repeatedly featuring remissions and
relapse. It can affect every joint in the body, and the
inammation causes arthralgia (tenderness and
spontaneous pain), swelling, heat sensation, and
dysfunction of joints, leading to loss of joint cartilage and bone, and eventually to joint destruction
with deformity. Finally, RA patients could result
inlocomotive syndrome that tends toward “bedridden” status, in which motor ability is signicantly
reduced due to joint destruction and deformation.
It is also characterized by the presence of a
variety of extra-articular symptoms, and should
be regarded as a systemic disease rather than an
osteoarticular disease. Among them, those with
vasculitis are designated as malignant RA (MRA)
(this is a diagnosis unique to Japan).
1.2 Pathoetiology
Although pathoetiology of RA is still to be
resolved, it is accepted to be caused or induced by
a complex combination of factors, including viral
and bacterial infections1, hormones, drugs, physi-
1
Viruses such as Human parvovirus B19, EB virus, and
Retrovirus, as well as Mycoplasma, Porphyromonas gin-
givalis, etc.
© 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_15
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Y. Matsukawa et al.
cal stress, smoking, and periodontal disease,
against a background of genetic abnormalities2.
1.3 Epidemiology
It is estimated that 0.5% to 1% of the world population is affected, although there are racial differences.
The ratio of males to females is reported to be 1:3 to
1:4, with a little difference among races or regions.
The incidence is lower in Asians and Hispanic than
in Caucasians. According to patients’ survey conducted by the Japanese Ministry of Health, Labour
and Welfare (MHLW) in its FY 2018 report (rst
Committee on Rheumatism and Other Related
Diseases), the estimated number of patients in FY
2014 was 33.6/1,000, which would be about 4.3
million if the total population is just under 130 million3. The total number of patients is on the rise and
has increased 1.2 times in the last 20years.
1.4 Pathophysiology
It is accepted that the inammation is induced by
various cytokines such as TNF-α produced by the
abnormally proliferated synovium, as well as by
inammation-inducing substances such as prostaglandins and leukotrienes.
articular destruction progresses and nally leads to
functionless deformity. We therefore have to establish the most suitable anti-rheumatic strategy as
soon as possible. The frequently affected joints are
the proximal interphalangeal joints, metacarpophalangeal joints, hand/shoulder/knee joints, and
metatarsophalangeal joints. As the lesion progresses, deformities unique to RA such as swanneck deformity, button hole deformity, and ulnar
deviation, are completed.
Extra-articular manifestations include (1) subcutaneous nodules (rheumatic nodules): they appear
on the extensor side of the joint where pressure is
applied, but can occur anywhere in the body; (2)
interstitial pneumonia, pleurisy, and intrapulmonary
rheumatic nodules (which must be differentiated
from lung cancer); (3) eye manifestations: uveitis
and episcleritis; (4) neurologic manifestations: carpal tunnel stenosis, paresthesia, motor paralysis,
and vertigo due to neck deformity; (5) vasculitis:
skin ulcer; and (6) renal failure(mainly due to ADE).
1.6 Diagnosis
The diagnosis should be established by referring
to the ACR/EULAR classication criteria after
conrming arthritis and various symptoms, and
taking into account blood tests and imaging studies (Table15.1) [3].
1.5 Symptoms ofRA
The initial symptoms are morning stiffness and
symmetrical, multiple, and migratory arthralgia. In
addition, it should be noted that patients with temporomandibular arthritis tend to visit a dentist. RA
should be considered when polyarthralgia persists
for more than 1 month and cannot be explained by
other diseases4. Initial changes are limited to articular malfunction due to swelling, redness, warmth,
and pain, but when RA is insufciently controlled,
2
It has been suggested that class II MHC, especially
HLA-DR antigens, are involved.
3
This number is higher than the previous estimates of
700,000 to 1,000,000, but it is close to the actual number
because it is based on patients who visited medical
institutions.
4
RA cannot be ruled out only because it is monoarthritis.
1.7 Clinical Examination
Anti-cyclic citrullinated peptide (Anti-CCP)
antibody, rheumatoid factor (RF), CRP, and
erythrocyte sedimentation rate (ESR), are
required for diagnosis (Table15.1), and in addition, the destruction of articular cartilage should
be evaluated by matrix metalloproteinase-3
(MMP-3). Serum complement titer (CH50) is
also useful in assessing RA activity.
1.8 Imaging Findings ofRA
Although plain radiography is the basic method,
it is insufcient for early diagnosis because it
only conrms the established anatomical
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Table 15.1
Rheumatoid arthritis classication criteria. The 2010 ACR/EULAR classication criteria (American
College of Rheumatology/European College of Rheumatology classication criteria). Clinically observed synovitis
(joint swelling) in one or more joints that cannot be explained by any other disease is graded A–D
A: Joint involvement
1 large joint
a
(0)
2–10 large joints (1)
1–3 small joints (with or without involvement of large joints)
b
(2)
4–10 small joints (with or without involvement of large joints) (3)
>10 joints (at least 1 small joint) (5)
B: Serology
c
Negative RF and negative ACPA (0)
Low-positive RF or low-positive ACPA (2)
High-positive RF or high-positive ACPA (3)
C: Acute-phase reactants
Normal CRP and normal ESR (0)
Abnormal CRP or abnormal ESR (1)
D: Duration of symptoms
<6weeks (0)
≥6weeks (1)
A score of 6 or more classies it as rheumatoid arthritis. AC PA anti-cyclic citrullinated peptide antibody
a
Large joints refers to shoulders, elbows, hips, knees, and ankles
b
Small joints refers to the metacarpophalangeal joints, proximal interphalangeal joints, second through fth metatarso-
phalangeal joints, thumb interphalangeal joints and wrists
c
Low-positive refers to IU values that are higher than the upper limit of normal (ULN) but ≤3 times the ULN for the
laboratory and assay; high-positive refers to IU values that are >3 times the ULN for the laboratory and assay
Fig. 15.1 Plain radiographs of both toes at the time of the rst visit to RA: bone erosion limited to the head of proximal
phalanx of the right fth toe
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Fig. 15.2 One year
after the start of MTX,
bone erosion extends to
the left 4/5 toes
Fig. 15.3 Right carpal
bone lumping is
observed
Y. Matsukawa et al.
changes. Narrowing of the joint space indicates
destruction of articular cartilage, and bone erosion indicates destruction of bone (Figs.15.1 and
15.2). In the terminal stage of RA, the constituent
bones of the joint would be fused into a mass and
no longer could maintain the articular function
(ankylosis) (Fig.15.3). Recently, articular echography and contrast-enhanced MR have been used
to visualize ongoing inammation.
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1.9 Treatment
Drug therapy is the basic treatment, but rehabilitation and surgery are also essential to improve
patients’ quality of life.
Non-steroidal anti-inammatory drugs
(NSAIDs) and corticosteroids are used for symptomatic relief, and disease-modifying antirheumatic drugs (DMARDs) have been developed
to control RA. Currently, methotrexate (MTX) is
accepted as the key drug of rst choice, and the dose
can usually be increased to 16mg/week in Japan.
Biologics should be considered for patients with
insufcient response to MTX or with
contraindications to MTX such as interstitial pneumonia or renal dysfunction. Biologics are injectable drugs that effectively control RA by inhibiting
the action of cytokines such as TNF-α, IL-1/IL-6/
IL-8, and CTLA4. Oral Janus kinase (JAK) inhibitors, which are as effective as biologics, can also be
used. However, due to their potent immunosuppressive effects, consideration for tuberculosis and
viral infections is essential5. Both biologics and
JAK inhibitors are expensive and are not recommended for patients who cannot afford them.
Tacrolimus is another kind of immunosuppressive
agent commonly used. Adrenocorticosteroids have
a potent anti- inammatory effect and are used during remission induction, but long-term administration should be avoided because of side effects.
Other classical DMARDs are applied in mild cases
(salazopyrin, gold formulations, penicillamine,
etc). All of RA treatments suppress the immune
response, we therefore should always pay attention
to compromised infection.
of RA in the TMJ varies from 5 to 86%, depending on each report, that is probably because there
are no clear diagnostic criteria for rheumatoid
arthritis of the TMJ (TMJ RA). Symptoms of
TMJ RA correlate with the duration and severity
of RA, but are less severe and progress more
slowly than in other joints. Incidentally, in rare
cases, RA symptoms can rst occur in the
TMJ.In the early stage of the disease, however, it
is difcult to distinguish RA symptoms from
those of temporomandibular joint disorder
(TMD), especially TMJ osteoarthritis (OA),
because there are no characteristic imaging ndings. Therefore, in the cases of RA which symptoms rst occur in the TMJ, the denitive
diagnosis of RA may be established after the
development of systemic symptoms and/or
polyarthritis.
On the other hand, it is important to establish
the denitive and start treatment as early as possible because RA can lead to serious conditions
such as progressive condylar resorption and
ankylosis of the TMJ (Figs.15.4 and 15.5). The
viewpoints for clinical differential diagnosis
Fig. 15.4 Bony ankylosis of the TMJ due to RA
1.10 Notes fromDentistry
Perspective
YoshikiHamada
1.10.1 Rheumatoid Arthritis of the
Temporomandibular Joint [5–9]
Rheumatoid arthritis (RA) also affects the temporomandibular joint (TMJ), and the frequency
5
Hepatitis B reactivation (de novo hepatitis) during and after
quitting of biologics or MTX has become a serious problem
because of the high mortality. It is essential to check for
hepatitis B before initiation of biologics and MTX.
Fig. 15.5 Condylar resorption due to RA
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between RA and TMJ OA are: (1) worsening of
symptoms over time without response to the standard treatment for TMD; (2) spontaneous pain
and tenderness in the TMJ area; and (3) unilateral
onset of symptoms on the opposite side. If symptoms develop in other joints, the patient should be
immediately referred to a rheumatologist.
The symptoms of TMJ RA depend on the
severity of RA, but the basic treatment is same as
that for TMD.In the advanced case with ankylosis of the TMJ or open bite with retrotrusive mandible due to severe condylar resorption, surgical
mobilization of TMJ, orthognathic surgery,
reconstruction of the condylar process, or articial TMJ replacement is indicated to recover jaw
function and occlusion.
1.10.2 Methotrexate-Associated
Lymphoproliferative Disease
(MTX-LPD) andRA DrugInduced Stomatitis
Currently, the basic concept of treatment for RA
is to suppress or delay the onset of dysfunction
due to joint destruction as much as possible, and
methotrexate (MTX), an immunosuppressive
agent, is recommended as a standard drug for this
purpose. On the other hand, serious side effects
include acute interstitial pneumonia, myelosuppression and associated infections, and MTXassociated lymphoproliferative disorders
(MTX-LPD).
In the oral cavity, in addition to stomatitis
caused by RA drugs such as MTX, there are several reports of ulceration caused by MTX-LPD
(Fig.15.6), which may be accompanied by bone
exposure, and commonly diagnosed as histopathological diffuse large B-cell malignant lymphoma. Clinically, local pain and contact pain at
the ulcer site are observed, and systemic symptoms, including fever and weight loss, are recognized. In addition, elevated IL-2R level is often
observed, and if its level is abnormally high of
exceeding 1000U/mL, it is necessary to consider
the possibility of existence of other undetected
lesions in the areas outside of oral cavity.
As a general rule, MTX-LPD is treated with
MTX withdrawal, and if no remission is observed,
chemotherapy is generally considered after con-
Y. Matsukawa et al.
Fig. 15.6 Ulceration of the left oor of mouth due to
MTX-LPD. (Courtesy of Dr. Toshikatsu Horiuchi,
Department of Oral and Maxillofacial Surgery, Saiseikai
Yokohamashi Tobu Hospital)
sultation with a hematologist or other physician,
but radiotherapy may be applied depending on the
histological type. Regarding the prognosis, it has
been reported that remission rate of 21 to 60% can
be achieved with drug suspension alone, but recurrence occurs in 33 to 67%. On the other hand, a
review of 24 Japanese cases of MTX- LPD in the
oral cavity reported a remission rate of 92%.
Although the pathogenesis of MTX-LPD is
unclear, EBV-positive patients account for more
than half of the cases, and it has been suggested
that EBV, which has the ability to proliferate
and transform B cells, causes lymphoma under
the condition of MTX-induced immunosuppression. It has also been reported that RA-related
biologics may be a cause of MTX-LPD, and that
RA itself increases the risk of developing
LPD.On the other hand, no signicant ndings
have been found in relation to the duration and
dosage of MTX and concomitant medications
such as prednisolone and bisphosphonates.
2 Collagen Disease [10–13]
NoriyukiSeta
2.1 Systemic Lupus
Erythematosus: SLE
2.1.1 Disease Overview
It is one of the most common collagen diseases
and causes damage to multiple organs due to the
production of a variety of autoantibodies. The
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