Division of Periodontics and Dental Hygiene

DENT 430 Periodontics

CASE OF

MR. IEN KASVU

CASE DOCUMENTATION
October 13th and 20th, 2015

Case Author: Dr. H. Larjava

Consulting Experts:
Drs. L. Hakkinen, E. Putnins
Revised 2003, Dr. C. Oakley in consultation with Dr. H. Larjava

Learning objectives of this case are listed below:

DIVISION
ORAL PATHOLOGY

BASIC SCIENCE OBJECTIVES

The student should be able to:
Describe the etiology, pathogenesis, histopathology, and clinical features of oral mucosal
inflammatory hyperplasias

ORAL BIOLOGY

Given a description of a specific dental treatment the student will be able to judge its
effects on living oral tissues, using a biological principle of treatment
Given a condition involving abnormal loss or gain of oral tissues the student will be able to
recognize its possible causes
The student will be able to describe the different biochemical and cellular aspects of
inflammation and tissue repair
The student will be able to define the basic structures of oral mucosal tissues and to
describe factors controlling their turnover in health and disease.

ORAL HISTOLOGY

The student should be able to explain the basic pathophysiology and clinical significance regarding
dental management of the following diseases:
organ transplantation (immune suppression)
hypertension
lichenoid mucositis suspected drug associated lesions
Biology of normal structure-function relationships of the oral mucosa

PERIODONTICS

1.

Describe the etiological factors associated with gingival enlargement & overgrowth (idiopathic,
systemic diseases, drug-induced, local factors).

2.

Describe the need for prophylactic antibiotic coverage in patients with special medical needs.

3.

Explain the appropriate pre-surgical management for patients exhibiting gingival overgrowth.

4.

Describe the surgical management of gingival overgrowth.

5.

Describe the appropriate supportive periodontal therapy required for patients exhibiting
gingival overgrowth.

ORAL MEDICINE

PROSTHODONTICS

ORAL SURGERY

The Division of Prosthodontics offered a number of lectures that are still relevant to our
competencies yet the information is not offered in the plans currently underway for the new
curriculum.
Prevalence and Management of Pathoses Associated with Oral Prostheses

Understand how concurrent medical problems may influence the patients treatment plan
List relative and absolute medical contraindications to tooth extraction in general dental
practice
Describe healing of oral soft tissues by primary or secondary intention
Assess the complexity of surgical removal of a third molar by clinical and radiographic
methods
Describe the surgical procedures available to improve the edentulous alveolar ridge prior to
denture construction
Provide relevant information to a patient in order to obtain informed consent
Identify abnormal oral mucosa, and know how to investigate its aetiology

DENT 430 Perio: Ien Kasvu Case Documentation (2015)

The Case of Mr. Ien Kasvu

The purpose of this case is to emphasize the relationship between gingival overgrowth
and the systemic medication in a medically compromised patient who also is in the need
of a new maxillary denture after pre-prosthodontic surgery. In addition, management of
an unerupted mandibular third molar that has a connection to oral cavity and is located in
close proximity to alveolar nerve should be discussed.
Mr. Kasvu is a retired schoolteacher who had a massive coronary infarct (heart attack)
about 14 years ago. This infarct resulted in severe hypertension (very high blood pressure)
that led to kidney failure. Over the years Mr. Kasvu has received dialysis treatment for
about three years and was placed on the waiting list to receive a kidney transplant.
Finally, about nine years ago a match was found and a transplant was successfully
performed. As a non-rejection therapy he received very high doses of cyclosporine (800
mg bid). The dose was gradually reduced to 500 mg bid and finally to the current dosage
of 75 mg bid. Additional immunosuppressant therapy includes Imuran 100 mg x 1, and 5
mg prednisone (every second day). His blood pressure is maintained at 140/90 using
Captopril (angiotensin inhibitor, anti-hypertensive, 15 mg tid) and Adalat (nifedipine, Cachannel blocker, antihypertensive, and 30 mg x 1). In addition, he takes Sotalol
(antiarhythmic, 18 mg bid). It is known that both cyclosporine and nifedipine alone can
cause gingival overgrowth. Together, they appear to have an additive effect.
Mr. Kasvu has a maxillary complete denture that was fabricated before he received the
transplant. There is a considerable amount of floppy overgrown tissue on the ridge and
the palatal tissue appears erythematous. Obviously Mr. Kasvu is in the need of a new
denture or at least a reline. He has almost full dentition in the mandible. Tooth #48 is
unerupted (impacted) but has a connection into the oral cavity. The apex of 48 is located
in close proximity to the alveolar nerve. He has only occasionally seen his dentist who
has recommended that he should see a gum specialist because his gums are overgrown.
Because of financial reasons he has not seen a specialist but has now referred himself to
the UBC Graduate Periodontics clinic. An incidental finding made at the Graduate clinic
also leads to a diagnosis of lichenoid mucositis in suspected association with prescribed
medications.
The students are to determine the relationship of the medications to gingival overgrowth,
management of medically compromised patient, surgical management of gingival
overgrowth and subsequent maintenance program. In addition, students are expected to
develop a plan of referral for pre-prosthodontic ridge surgery and a new denture/reline.
Risks of retaining/removing tooth #48 should also be discussed.
Learning Objectives
Explain the pathogenesis of gingival overgrowth.
Describe the surgical management of gingival overgrowth.
Explain principal aspects of wound healing
Describe the maintenance program for patients with gingival overgrowth.
Describe the relationship between systemic medication and gingival overgrowth.

DENT 430 Perio: Ien Kasvu Case Documentation (2015)

Learning Objectives contd

Describe the relationship between systemic medication and lichenoid reactions.
Describe the clinical management of medically compromised patient.
Recognize the need for pre-prosthodontic surgery.
Explain the risks and advantages of 3rd molar extraction in medically
compromised patients.
Organize Mr. Kasvus case using the SOAP principles

DENT 430 Perio: Ien Kasvu Case Documentation (2015)

The Case of Mr. Ien Kasvu

Ien Kasvu is a 72-year-old Caucasian male who is a retired teacher. He refers himself to
the graduate Periodontics clinic with a chief complaint that his gums are swollen and
bleed. In addition, his denture is somewhat loose and it bothers him while eating. The
back cheeks feel rough and sometimes sore, especially after eating spicy food.
Please refer to Exhibit 1 Intra-oral photographs
1. a) Describe the appearance of the gingiva.
b) Are these physiologic gingival contours?
No, these are not physiologic gingival contours. Papillae are significantly
enlarged and cover the clinical crowns. The enlarged contours of the papillae
appear to coalesce over the facial crown aspects in a cleft pattern. Significant
erythema of the gingiva is not evident and the gingival tissue texture is likely
fibrotic rather than edematous.
c) What has happened to the shape/size of the papillae?
d) What is the color of the gingiva?
e) What is the suspected texture of the gingiva?

Guiding Question:
Draw attention to the swelling/enlargement of the papillary gingiva in the anterior
mandible, and the labial gingival cleft formation if you have not already observed it.
Discuss what they think is the cause of the gingival overgrowth and cleft formation.
2. (a) List the potential etiologies for gingival overgrowth.

Periodontal infection (periodontal disease or abscess)

Trauma - ex gingival abscess if restricted to the gingiva
Foreign body blockage of sulcus or periodontal pocket
Violation of biological width (restorations too close to bone)
Idiopathic gingival fibromatosis
Tumor (leukemia, epulis, pyogenic granuloma, fibroma etc.)
Hormonal (pregnancy, puberty gingivitis; pyogenic granuloma)
Vitamin C deficiency
Plasma cell gingivitis
Drug-induced overgrowth

(b) List potential etiologies for gingival clefting.

Artificially caused by swelling (enlargement) of the papillary gingiva (pseudopockets)
Improper use of dental floss
Wrong brushing technique

DENT 430 Perio: Ien Kasvu Case Documentation (2015)

 Trauma (accidental, habit)

(c) Describe the appearance of the buccal mucosa. Is this appearance within
normal limits?
The appearance of the buccal mucosa is not within normal limits. There are bilateral
changes of the posterior buccal mucosa including erythema and white striae/plaques.
On the right side, the striae are more numerous and prominent and there is less
erythema a compared to the left side where the erythema is more pronounced and the
white striae are less prominent in appearance and less numerous.
(d) At this point, do you have enough information about Mr. Kasvu in order to
rule in/rule out any diagnoses or etiologies for
(i) the appearance of the gingiva
(ii) the appearance of the buccal mucosa?
No.
(e) What additional information is required?
Detailed medical/dental history
Detailed extra-oral/intra-oral examination including soft tissue, dental and
periodontal examination
Test to determine if the white striae/plaques are adherent
Mr. Williams completes the health questionnaire and you assist the graduate student to
review the history by asking him pertinent questions to clarify his present and past
medical status. He reports taking antibiotics before the appointment as recommended by
his physician; he has the bottle with him. Next, you assist the graduate student to conduct
a clinical examination (see clinical findings) and take appropriate radiographs.
Please refer to Exhibit 2: the medical history forms, odontogram and radiographs.
NOTE: the Health Questionnaire includes information provided directly by Mr. Kasvu as
well as information obtained by the resident through interview of Mr. Kasvu.

DENT 430 Perio: Ien Kasvu Case Documentation (2015)

EXHIBIT 2: HEALTH QUESTIONAIRE

DENTAL INTERVIEW AND CLINICAL EXAMINATION
CHIEF COMPLAINT - my gums are swollen and they bleed. My upper denture is loose.
Rough cheeks that sometimes feel sore when I eat spicy foods

DENTAL HISTORY
Frequency of visits the dentist Attended irregularly as a child, had all maxillary
teeth extracted because of caries when he was between 50-60, most of
mandibular teeth were crowned about 10 years ago. Has been irregular
patient for the last 10 years.
History of present condition His dentist had recognized swollen gums several
years ago and recommended to see a specialist. Did not go because of the
financial reasons. Upper denture has become loose over the last couple of
years
Last dental cleaning More than 18 month ago
Family history of caries and/or periodontal disease cannot remember
Oral hygiene Uses a regular brush and changes it twice a year.
Brushes 2x/d for about 1 minute. Uses wooden toothpicks for interdental
cleaning wherever they fit.
SOCIAL/FAMILY HISTORY
Ien Kasvu is a 72-year-old Caucasian male who is a retired teacher. His wife is also a
retired teacher. They have several children and they spend a lot of time with their grand
children.
MEDICAL HISTORY

Circle One
DK - Dont know

1) Who is your family physician? I go to Vancouver General, Nephrology Unit, every 3

months
2) Are you taking or have you taken any drugs within the past year Yes No DK
(ex. tranquilizers, steroids, aspirin) List: Mr. Kasvu had a massive heart attack about
14 years ago. This heart attack resulted in very high blood pressure that over the years
lead to kidney failure. Mr. Kasvu then received dialysis treatment for about three years
and was placed on the waiting list to receive kidney transplant. Finally, about nine years
ago a match was found and a transplant was successfully implanted. As a non-rejection
therapy he received very high doses of cyclosporine (800 mg bid). The dose was
gradually reduced to 500 mg bid and finally to the current dose of 75 mg bid. Other
immunosuppressants in use are Imuran 100 mg x 1, and 5 mg prednisone (every second
day). His current blood pressure is 140/90 with Captopril (15 mg tid) and Adalat (30 mg
x 1). In addition, he takes Sotalol (18 mg bid) for his heart condition.
3) Do you have any in-dwelling medical devices (hip or knee
Yes No DK
replacement, heart valve, etc)?

DENT 430 Perio: Ien Kasvu Case Documentation (2015)

4) Do you have or have you had any of the following conditions:

Asthma
Yes No DK
Rheumatic Fever
Yes No DK
Heart murmur
Yes No DK
Heart problems
Yes No DK
Heart attack
Yes No DK
High blood pressure
Yes No DK
Heart surgery
Yes No DK
Stroke
Yes No DK
Scarlet fever
Yes No DK
Anemia
Yes No DK
Abnormal blood count
Yes No DK
Hay fever
Yes No DK
Hives or skin rash
Yes No DK
Tumor or growth
Yes No DK
Frequent headaches
Yes No DK
Sinusitis
Yes No DK
Radiation therapy Yes No DK
HIV

5) Has your general health changed in the past year?

Lupus
Tendency to faint
Epilepsy
Diabetes
Seizures or convulsions
Jaundice
Hepatitis (liver disease)

Yes No DK
Yes No DK
Yes No DK
Yes No DK
Yes No DK
Yes No DK
Yes No DK
Thyroid/parathyroid disease Yes No DK
Kidney problems
Yes No DK
Arthritis or rheumatism Yes No DK
Ulcers
Yes No DK
Tuberculosis
Yes No DK
Emphysema
Yes No DK
Herpes
Yes No DK
Glaucoma
Yes No DK
Prostate disorders
Yes No DK
Yes No DK
Yes

6) Has your weight changed in the past year?

Yes
7) Have you ever had any serious illnesses or major operations?
Yes
8) Have you had any bleeding associated with previous tooth
Yes
extraction, surgery or trauma?
9) Do you heal slowly?
Yes
10) Have you ever had any allergies (food, drugs, latex, etc)?
Yes
11) Have you ever had an asthmatic attack?
Yes
12) Are you ever short of breath or have chest pain after mild exertion?
Yes
13) Do your ankles swell?
Yes
14) Are you thirsty much of the time?
Yes
15) Has anyone in your family ever had diabetes? Who?
Yes
16) Do you have a persistent cough or do you cough up blood
Yes
17) Do you consider yourself a nervous person?
Yes
18) Have you ever had surgery or treatment for a tumor or growth of
Yes
your head, mouth or lips?
19) Do you smoke?
Yes
20) Vitals
Blood pressure 140/90
Pulse 80
Resp 16

No

DK

No DK
No DK
No DK
No
No
No
No
No
No
No
No
No
No

DK
DK
DK
DK
DK
DK
DK
DK
DK
DK

No

DK

Medical Summary: See above. His physician has prescribed Amoxicillin 500 mg and
asked him to take two tablets one hour before the dental visit.

DENT 430 Perio: Ien Kasvu Case Documentation (2015)

CLINICAL EXAMINATION
Extraoral exam
1) General appraisal
2) Structures of the face
3) TMJ
4) Salivary glands
5) Regional lymph nodes
6) Structures in the neck
7) Neurologic deficit
8) Paranasal sinus
9) Skeletal malrelationships
10) Other findings

no abnormalities noted
no abnormalities noted
no abnormalities noted
no abnormalities noted
no abnormalities noted
no abnormalities noted
no abnormalities noted
no abnormalities noted
no abnormalities noted
none

Intraoral exam: See intraoral pictures.

1) Lips and labial mucosa
2) Buccal mucosa

no abnormalities noted
bilateral erythema; adherent and palpable white
striae/plaques
3) Mucobuccal fold
posterior mandibular: erythema, white striae/ plaques
4) Hard palate
Palatal mucosa is floppy and swollen on the crest
from #14-24 area, red spots of inflammation present
5) Soft palate and uvula
no abnormalities noted
6) Oropharynx and nasopharynx
no abnormalities noted
7) Tongue
no abnormalities noted
8) Floor of mouth
no abnormalities noted
9) Muscles of mastication
no abnormalities noted
10) Occlusion classification
N/A (CUP)
11) Other findings
none
Trauma
1) Soft tissue
2) Bone
3) Teeth
4) Date of injury
Habits

none
none
none
none
Fairly good oral hygiene (65% effective)

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Review the dental and medical history, clinical examination and radiographs.
Review the SOAP format.
The SOAP method is one approach that may be used to assist clinicians summarize a
patients case in an orderly manner. The SOAP method is useful in separating symptoms
from signs and in organizing observations, diagnoses and treatment planning.
SOAP is an abbreviation for

Subjective information: information provided by the patient such as

Medical history
Oral/dental history
Chief complaint
Symptoms
Stated preference for treatment/non-treatment, etc

Objective information: the observations and findings of the clinician such as

Patients vital signs

Clinical findings (signs)
Radiographic findings
Any test results (eg caries susceptibility tests/Strept mutans levels)

Assessment: the clinicians interpretation of the subjective and objective information

Diagnoses
Etiology
Prognosis

Plan: the course of action or treatment plan proposed and/or performed by the clinician,
based upon and supported by the subjective information/objective information and
assessment above
May include several treatment options
Should include documentation that the options for treatment were in fact presented
and discussed with the patient
Includes details of actual treatment delivered: eg: amount, type and location of local
anesthetic administered; site and type of treatment; time required for treatment where
appropriate; specifics of oral hygiene instruction, etc.
3. a) Using the SOAP format, list the Subjective Information:
Chief Complaint:

gums swollen and bleed; loose denture; rough cheeks and occasional
soreness of back cheeks with eating spicy foods

Medical findings
Heart attack 14 years ago
Kidney transplant 9 years ago
High blood pressure (medicated)
Immunosuppressant therapy to prevent transplant rejection

DENT 430 Perio: Ien Kasvu Case Documentation (2015)

b) List Mr. Kasvus medications and include:

i) the mode of drug action,
ii) side-effects of relevance to the dentist, and
iii) possible interactions with drugs of relevance to dental practice.
4. a) Why did Mr. Kasvus physician prescribe prophylactic antibiotics?
Mr.Kasvu is immunocompromised (CSA, imuran, prednisone) and bacteremia caused by
invasive dental procedures (such as periodontal probing) could lead to destruction of the
transplant.
b) Mr. Kasvu was prescribed amoxicillin 500 mg; 2 tabs one hour before the
dental visit. Is this an appropriate regime?
Tutors should encourage students to discuss the current recommendations for
prophylactic antibiotics (conditions, which antibiotics and the usage).
c) If Mr. Kasvu were receiving haemodialysis, would prophylactic antibiotics be
recommended?
If the patient has received haemodialysis then there are often foreign materials in the
vasculature that are prone to infection. Also, in chronic renal failure they can become
hypercalcaemic & many have calcifications within the endocardium.
5. List the Objective findings:
Intra-Oral and Radiographic findings:
Relatively good oral hygiene (considering the gingival conditions) 65%
Gingival inflammation
Gingival overgrowth
Generalized 5-7 mm gingival pockets
Loose upper denture
Inflammation of the hard palate
Palatal tissue overgrowth at the edentulous ridge
Erythema, white striae bilaterally on posterior buccal mucosa, mandibular
mucobuccal folds
Periapical lesion #36
Unerupted impacted 48 associated with 10 mm pocket distal to 47
Note: The periapical lesion is not a learning issue in this case nor is the denture design.

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6. What is your Assessment of this case? List the Diagnoses for Mr. Kasvu; use
Armittage 1999 as a guide.

Diagnoses for Mr. Kasvu, as per Armitage 1999

Gingival Diseases
A. Dental plaque-induced gingival diseases
1. Gingivitis with local contributory factors gingival enlargement
2. Gingival Diseases modified by medications
a. drug-influenced gingival diseases
i. drug-influenced gingival enlargements CSA, adalat
B. Non plaque-induced gingival lesions
1. Gingival Diseases of fungal origin
a. Candida-species infections - denture stomatitis
2. Gingival manifestation of systemic condition
a. mucocutaneous disorder * include differential diagnosis*
- lichen planus?
- Drug-induced lichenoid reaction?
- Candidiasis?
- Discoid lupus erythematosis (DLE)?
- Frictional keratosis?
- erythroplakia?

Chronic Periodontitis
A. Localized advanced 47 distal

Developmental or Acquired Deformities and Conditions

A. Conditions on Edentelous Ridges
Gingival/soft tissue enlargement denture hyperplasia
B. Periapical periodontitis tooth 36
C. Impacted 48 with communication to oral cavity

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11

7. What are the possible etiologies (primary and secondary/contributory) for each
diagnosis?
Diagnosis
Gingival inflammation
compromising

Primary Etiology
plaque

Secondary/Contributory Etiology
gingival enlargement
OH
xerostomia secondary to captopril,
adalat, prednisone

Gingival enlargement

Diagnosis
Denture stomatitis

nifedipine (adalat)
plaque; plaque accumulation favored
Cyclosporine (CSA) by nonphysiologic gingival contours
and xerostomia
Primary Etiology
Secondary/Contributory Etiology
CUD
inadequate denture hygiene; possible
24/7 wear; poorly-fitting CUD
candida

immunosuppression: prednisone,
imuran, CSA
xerostomia secondary to captopril,
adalat, prednisone
increased risk due to need for
antibiotic prophylaxis; coverage
during surgical treatment

lichen planus/DLE

unknown

lichenoid mucositis

drugs?

candidiasis
frictional keratosis
erythroplakia

candida
trauma
unknown

Chronic Periodontitis
tooth 47

Any drug has potential to elicit

lichenoid reaction; captopril has
high incidence

plaque
mesioangular impacted
48

Denture Hyperplasia

poorly fitting CUD

Periapical Pericoronitis
Impacted 48

anaerobic flora
inadequate jaw length

DENT 430 Perio: Ien Kasvu Case Documentation (2015)

? drug-influenced CSA, adalat?

Candida
Role of traumatic occlusion?

12

8. Discuss the effects of cyclosporine and nifedipine upon gingival overgrowth.

(a) Is there is a relationship between plaque, CSA and adalat?
Poor oral hygiene aggravates the conditions. Overgrowth can, however, be seen also with
patients with excellent oral hygiene.
(b) Is there is a dose-response relationship between CSA, adalat and the amount of
gingival enlargement?
Generally, yes.
(c) Review the modes of action of CSA and nifedipine. Discuss the clinical features
and epidemiology of gingival enlargement associated with CSA and nifedipine.
It is not expected that the students know this but for the 1st session they should suspect
that Mr. Kasvus medication might play a role in the initiation of gingival overgrowth.
They are to study for the 2nd session what his medications do and how cyclosporine and
nifedipine can cause gingival overgrowth and are there any other drugs with similar side
effects (phenytoin, other Ca-channel blockers used for high blood pressure medication). .
For more details of the action of these drugs on gingiva, please read the following:
Nifedipine
Nifedipine is a calcium channel blocker that is used in the treatment of angina and hypertension. Its function
is to inhibit the entry of calcium ions into cells. The reduction of available calcium reduces myocardial cell
contractility and oxygen consumption. This results in the relaxation of coronary vascular smooth muscle, dilation
of coronary and peripheral arteries, and an increase in myocardial oxygen delivery in angina patients (Seymour
and Heasman, 1988; Gage and Pickett, 1997). At a cellular level, nifedipine blocks the breakdown of ATP by
calcium-dependent ATPase, which results in a decrease of high energy phosphate consumption, mechanical
tension, and oxygen requirements of the myocardium (Hillis, 1980).
The systemic side effects of nifedipine include dizziness, flushing, headaches, weakness, nausea, muscle
cramps, tremor, peripheral edema, joint stiffness, dermatitis, pruritus, and urticaria (Lederman et al., 1984). In
addition, gingival enlargement has been documented as a oral side effect caused by the administration of
nifedipine (Lederman et al., 1984; Ramon et al., 1984). The incidence of nifedipine-induced gingival
enlargement has been reported as 6.4% (Ellis et al., 1999), 15% (Barak et al., 1987), 20% (Barclay et al., 1992),
29% (Tavassoli et al., 1998), and 44% (Nery et al., 1995).
The clinical presentation of nifedipine-induced enlargement closely resembles the presentation of dilantininduced gingival enlargement (Seymour and Heasman, 1988). The overgrowth usually occurs within one to two
months after the initiation of the medication (Seymour, 1991). The site of enlargement is typically the labial
gingiva of the upper and lower teeth (Seymour and Heasman, 1988). Although many authors have reported no
evidence of enlargement in edentulous areas (Seymour and Heasman 1988; Barclay et al., 1992; Ramon et al.,

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1984), a recent study reported one case of nifedipine-induced gingival overgrowth in an edentulous area
(Tavassoli et al., 1998). The pattern of overgrowth, which is limited to the attached gingival tissue, begins as a
swelling of the interdental papillae. As the enlargement progresses, the papillae may then coalesce and cover the
surface of the tooth. The enlarged tissues, which are separated from the gingival margin by a linear groove,
appear edematous and hyperemic. In severe cases, the tissue can extend over the crowns of the teeth and
consequently interfere with eating (Seymour, 1991).
It has been reported that a higher incidence of enlargement is evident in patients in their fourth decade
compared to patients in their fifth and sixth decade (Tavassoli et al., 1998; Nery et al., 1995). Males appear to
have a three times greater chance of developing clinically significant nifedipine-induced gingival overgrowth
compared to females (Ellis et al., 1999).

Cyclosporin
Cyclosporin, discovered by Borel in 1972, is a fungal metabolite produced by Trichoderma polysporum
Rifai and Cyclindrocarpon lucidum (Borel et al., 1976). The pharmaceutical companys initial goal was to create
a potent antimicrobial compound, but studies later revealed that cyclosporin had poor antimicrobial activity. It
was serendipitously discovered that cyclosporin had an inhibitory effect on the subpopulation of T-lymphocytes,
no effect on the humoral response, and low myelotoxicity (Borel et al., 1976; Britton and Palacios, 1982). The
pathway through which the T cell function is impaired is via specific inhibition of the synthesis of interleukin-2.
Other growth factors, which include interleukin-1(IL-1), lymphokine-3(IL-3), migration inhibitory factor(MIF),
gamma interferon (IFN-), lymphocyte directed chemotactic factor (LDCF), and macrophage activation factor
(MAF), have also been shown to be inhibited by cyclosporin (CPS, 1998).
The principle use of cyclosporin is the prevention of graft rejection in organ transplantation, but it is also
being used in other diseases which may have an altered cell-mediated immunological mechanism. Such diseases
include: type I diabetes mellitus (Stiller et al., 1983), primary biliary cirrhosis (Routhier et al., 1980), psoriasis
(Mueller and Herrmann, 1979), rheumatoid arthritis, erosive lichen planus, ulcerative colitis, and Crohns disease
(Daley and Wysocki, 1984), Behets disease (French-Constant et al., 1983). Gingival overgrowth was first
recognized in association with cyclosporin use while the medication was being evaluated in patients that had
received organ transplants (Starzl et al., 1980; Calne et al., 1981). It was observed that the pattern of overgrowth
was identical to that of phenytoin-induced overgrowth (Wysocki et al., 1983). The enlargement, which typically
occurs within three months of taking cyclosporin (Seymour et al., 1987), begins in the papillae area, and as with
phenytoin-induced overgrowth, the papillae appear to coalesce. The overgrowth is limited to the attached
gingiva, and in severe cases, the enlargement can extend coronally and interfere with speech, mastication, and
occlusion (Tyldesley and Rotter, 1984). It appears that the overgrowth is more common on the labial surfaces of
the teeth, and in the anterior regions of the mouth (Daley and Wysocki, 1984). Specifically, the overgrowth is
more common on the labial aspect of the canine teeth compared to the overgrowth around the central incisors
(Thomason et al., 1996a). The tissues are different from phenytoin-induced overgrowth in that the cyclosporininduced overgrowth appears more hyperemic (Seymour and Jacobs, 1992). Cyclosporin-induced gingival

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overgrowth has not been shown to occur in edentulous spaces (Somacarrera et al., 1994), nor does it occur in
edentulous patients (Friskopp and Klintman, 1986).
The incidence of cyclosporin-induced overgrowth has been reported as high as 70% (Daley et al., 1986),
though most authors concur that the incidence is approximately 30% (Seymour et al., 1987; Wysocki et al., 1983;
McGaw et al., 1987). There is a lower incidence of gingival overgrowth in bone marrow transplant patients
treated with cyclosporin than in renal transplant patients (Beveridge, 1983). Controversy exists regarding a
higher incidence of cyclosporin-induced overgrowth in children and adolescent patients. Some authors believe
that there is a higher incidence of overgrowth in this subset of patients (Daley and Wysocki, 1984; Karpinia et
al., 1996), whereas other authors disagree (Seymour and Smith, 1991). Cyclosporin-induced gingival overgrowth
does not appear to have any gender predilection (McGaw et al., 1987).

Cyclosporin and nifedipine-induced gingival overgrowth

Nifedipine and cyclosporin are frequently prescribed together for use by renal and cardiac transplant
patients (Thomason et al., 1993). In these cases, nifedipine is used to treat either primary or secondary
hypertension. The incidence of nifedipine and cyclosporin-induced overgrowth is greater than the incidence of
overgrowth in patients taking only one of the medications. Reports on incidence range from 48% to 60% (Slavin
and Taylor, 1987; Thomason et al., 1993; King et al., 1993; Margiotta et al., 1996). The prevalence of the
overgrowth appears to be similar when comparing gingival overgrowth in patients taking cyclosporin alone to
patients taking both cyclosporin and nifedipine, but the severity of the overgrowth in the combination patients is
increased (Thomason et al., 1993; Thomason et al., 1995). A study which reported on cardiac transplant patients
taking both cyclosporin and nifedipine found that males were more likely than females to have clinically
significant overgrowth. It was also shown that there was a significantly greater need (25-fold) to perform
gingival surgery on patients taking both medications, compared to patients only taking one medication
(Thomason et al., 1995). The increased risk for progression and recurrence of gingival overgrowth due to the
administration of both cyclosporin and nifedipine has been confirmed by other studies (Bkenkamp et al., 1994;
OValle et al., 1995).

9. What is causing overgrowth of the palatal tissue on the edentulous ridge? What
is causing the associated inflammation?
It has been only sporadically reported that medication (such as cyclosporine) is associated
with overgrowth of tissue in edentulous areas of the mouth. It is, however, possible. More
likely, the ill-fitting loose denture and possible trauma from occlusion are causing the
overgrowth. The inflammation underneath the denture might be associated with
mechanical irritation of the denture or Candida infection (denture stomatitis).
10. What are the histological features of gingival overgrowth?
Nifedipine-induced gingival overgrowth tissue.

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The histological appearance of nifedipine-induced gingival overgrowth tissue is similar to that seen in
phenytoin overgrowth (Marshall and Bartold, 1998). The features commonly seen in phenytoin overgrowth
include: acanthosis, evident as elongated rete ridges, hyperkeratosis and parakeratosis, and an increase in
frequency of epithelial islands in the connective tissue due to sectioning of the tissue. A ten-fold increase in the
epithelial width (normal width ranges between 0.3 to 0.5mm) has been reported (Van der Wall et al., 1985). The
appearance of the connective tissue varies according to the degree of inflammation and the stage of development
of the overgrowth. There appears to be an increase in the number of fibroblasts as well as an increase in the
formation of collagen fibers. Chronic inflammatory cells, specifically lymphocytes and plasma cells, are visible
in most phenytoin cases (Angelopoulos, 1975). Nifedipine-induced overgrowth shares the following features
with phenytoin-induced gingival overgrowth: slight to moderate hyperkeratosis, thickened spinous layer of the
epithelium, elongation of the rete ridges, fibrotic connective tissue with fibroblast proliferation, increased
numbers of capillaries with chronic perivascular inflammation, and abundant plasma cell, mast cell and
lymphocyte infiltration (Barak et al., 1987; Lucas et al., 1985; Ramon et al., 1984; Lederman et al., 1984). The
number of CD 1a-labelled Langerhans cells has been shown to be significantly lower in the sulcular epithelium of
nifedipine-induced gingival overgrowth samples compared to normal and immunosuppressive medication
induced gingival overgrowth samples (Nurmenniemi et al., 1999). The fibroblasts in the connective tissue are
considered active due to the presence of prominent rough endoplasmic reticulum and large cytoplasmic
secretory granules (Lucas et al., 1985).
Cyclosporin-induced gingival overgrowth tissue
Histologically, cyclosporin-induced gingival overgrowth tissue is very similar to phenytoin and nifedipineinduced overgrowth tissue (Wysocki et al., 1983). The epithelium demonstrates variable thickness, areas of
parakeratosis, and elongated rete ridges (Wysocki et al., 1983; Deliliers et al., 1986). Needle-like crystallite
structures, presumed to represent accumulated cyclosporin, as well as intact and degranulated mast cells, have
been identified within the gingival epithelium of patients exhibiting cyclosporin-induced gingival overgrowth
(Pisanty et al., 1990). The basal lamina is interrupted in areas where the epithelium has invaded the underlying
connective tissue, and it is in direct contact with a layer of collagen fibers (Mariani et al., 1996). The connective
tissue demonstrates increased numbers of fibroblasts, mast cells, plasma cells, as well as an increase in the degree
of vascularization (Rateitschak-Plss et al., 1983; Deliliers et al., 1986; Mariani et al., 1996). The helper/inducer
T lymphocyte (CD4) and the cytotoxic/suppressor T lymphocyte (CD8) ratio has been shown to be higher in
patients with cyclosporin-induced gingival overgrowth (OValle et al., 1994). In addition, the number of
epithelial cells with intraepithelial deposits of cyclosporin were found to be positively correlated with the degree
of inflammatory infiltrate of CD4+, CD8+ and CD68+ cells (OValle et al., 1994). The majority of mononuclear
cells found in this form of overgrowth tissue include monocytes and T-lymphocytes; virtually no B-lymphocytes
are seen (Friskopp et al., 1986). The fibroblasts, which have been described as resembling myofibroblasts
(Yamasaki et al., 1987), contain dilated ergastoplasmatic cisternae, which are characteristic of productive
behavior (Mariani et al., 1993). The amount of amorphous ground substance produced by the fibroblasts in

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cyclosporin-induced overgrowth tissue is higher than that found in normal gingival samples (Mariani et al.,
1996).

11. (a) What is the difference between hyperplasia and hypertrophy?

Hyperplasia = increased number of normal cells
Hypertrophy = increased size of constituent cells

(b) In summary, is gingival overgrowth due to hyperplasia or hypertrophy?

Epithelial component: acanthosis/increased thickness = hypertrophy
increased number islands, elongated rete ridges - hyperplasia
Connective component: number fibroblasts = hyperplasia
12. Discuss the possible pathogenesis of nifedipine and cyclosporin-induced gingival
overgrowth.
The pathogenesis of nifedipine and cyclosporin-induced gingival overgrowth is not fully known
or understood (Seymour et al., 1996; Marshall and Bartold, 1998). The multifactorial nature of
this process can be related to certain factors: genetic predisposition, pharmacokinetic variables,
alterations in the gingival connective tissue homeostasis, including the non-collagenous matrix
and the connective tissue metabolism, the indirect effect of nifedipine, and the presence of
dental plaque, inflammation and gingival bleeding (Pernu et al., 1992; Seymour et al., 1996).
Nifedipine-induced gingival overgrowth
Genetic predisposition may play a role in the occurrence of nifedipine-induced gingival overgrowth
because it has been shown that not all patients taking nifedipine will show signs of gingival overgrowth. Patients
are referred to as responders if they demonstrate medication-induced gingival changes (Seymour et al., 1996).
Responders may show differences in fibroblast function, drug receptor binding and drug metabolism. Fibroblasts
within one individual may show phenotypically distinct and functionally different subpopulations (Hassell and
Stanek, 1983; Hkkinen and Larjava, 1992). In vitro studies utilizing fibroblasts from nifedipine-induced
gingival overgrowth samples showed increased cell proliferation when fibroblasts were exposed to 1 g/ml
nifedipine for short (72 hours) and long (six weeks) term experiments. The increase in cell proliferation at six
weeks was concomitant with a decrease in proteoglycan synthesis (Willershausen-Zonnchen et al., 1994). The
results of this study support the findings of other in vitro experiments (Fujii et al., 1994; McKevitt and Irwin,
1995). Conversely, other in vitro experiments have shown that fibroblasts from nifedipine-induced gingival
overgrowth samples exposed to nifedipine did not proliferate at a rate any different from normal fibroblasts
(Nishikawa et al., 1991; Tipton et al., 1994). The production of glycosaminoglycans and fibronectin was not
different from that produced by normal fibroblasts, and the production of collagenase was decreased (Tipton et
al., 1994). Collagen production by fibroblasts derived from nifedipine-induced gingival overgrowth has been

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shown to increase (Tipton et al., 1994; Fujii et al., 1994; McKevitt and Irwin, 1995), remain unchanged
(Nishikawa et al., 1991), and decrease (Salo et al., 1990; Zebrowski et al., 1986). The high variability of the
results of these in vitro studies may be due to the genetic heterogeneity of the fibroblasts that can exist within one
patient. This has been confirmed by one study that demonstrated that individual fibroblast cell lines possess
many differing responses to external stimuli (Larjava and Uitto, 1987). The shortcoming of many of the in vitro
studies is that very few fibroblast cell lines were utilized, making the interpretation of the results difficult. The
determination of human lymphocyte antigen (HLA) expression has been examined in patients who exhibit
nifedipine-induced gingival overgrowth. These studies showed opposing results. One study did not find a
correlation between HLA expression and overgrowth (Margiotta et al., 1996), whereas the other found a trend for
the HLA-DR2+ patients to have more severe gingival overgrowth (Pernu et al., 1994). More studies are required
to definitively link HLA expression and fibroblast phenotype (Seymour et al., 1996). Other genetic variations
may include the function of the cytochrome P450 group (Seymour et al., 1996). It has been determined that the
cytochrome P450 genes display genetic polymorphism, which can result in interindividual variation in drug
metabolism (Gonzales, 1992). Such variation may have some influence on the development of gingival
overgrowth in certain individuals (Seymour et al., 1996).
Pharmacokinetic variables may play a role in the development of nifedipine-induced gingival overgrowth.
The primary action of nifedipine is the inhibition of calcium ion influx. It may be through this direct action on
the gingival cells that gingival overgrowth may result (Marshall and Bartold, 1998; Seymour et al., 1988). It has
been postulated that the physico-chemical profile of nifedipine (highly lipophilic) enhances its ability to interact
with the cells within the gingival tissue (Ellis et al., 1999). This hypothesis requires further studies to determine
its validity. Nifedipine is metabolized into two pharmacologically inactive metabolites. The primary metabolite
(95%) is dehydronifedipine, the secondary metabolite (5%) is the lactone derivative of nifedipine (CPS, 1999).
An examination of the effect of nifedipine and its metabolites revealed that the metabolites were not a risk factor
for the severity of gingival overgrowth in patients taking both cyclosporin and nifedipine (Thomason et al.,
1997). The dose and duration of nifedipine and its relationship to the prevalence of overgrowth has not been
fully determined. It has been reported that the dose and duration of nifedipine is both related (Tavassoli et al.,
1998), and not related to the presence of overgrowth (Barclay et al., 1992; Nery et al., 1995). Most authors agree
that individual sensitivity in metabolizing nifedipine is likely the main reason for the presence of overgrowth
(King et al., 1993; Tavassoli et al., 1998). It was proposed that the sequestration of nifedipine in the gingival
tissues may predispose patients to developing gingival overgrowth. This was supported by a study which
demonstrated nifedipine at higher concentrations in the gingival crevicular fluid (15-316 times) compared to that
found in the plasma in patients demonstrating nifedipine-induced gingival overgrowth (Ellis et al., 1992). A
subsequent study revealed that there was no difference between responders and non-responders with respect to
the detection and level of nifedipine concentration in the gingival crevicular fluid (Ellis et al., 1993). It was later
determined that the presence of inflammation and plaque were significantly related to the sequestration of
nifedipine in the gingival crevicular fluid of patients with gingival overgrowth (Ellis et al., 1995). In view of the
current findings, the concentration of nifedipine in the gingival tissues may provide some information regarding
the pathogenesis and manifestation of gingival overgrowth (Seymour et al., 1996).

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The alterations in the gingival connective tissue homeostasis may include the effect of nifedipine on
fibroblasts, as previously discussed. Other effects may include the effect of the medication on gene expression.
The expression of type VI collagen genes and the deposition of type VI collagen was found to be increased in
patients exhibiting nifedipine-induced gingival overgrowth (Shikata et al., 1993). The effect of nifedipine on
gene expression may play an important role in the pathogenesis of the overgrowth, but further studies are
required in this area (Seymour et al., 1996). In vitro experiments analyzing the effect of nifedipine on
proteoglycan synthesis have reported both increased synthesis (Saito et al., 1996), and decreased deposition of
proteoglycans by fibroblasts (Tipton et al., 1994; Willershausen-Zonnchen et al., 1994). Normal gingival tissues
exhibit a level of homeostasis in which collagen synthesis and degradation are balanced. In medication-induced
gingival overgrowth the normal metabolism of the connective tissue can be altered in many different ways
(Barclay et al., 1992). The collagenolytic signal from inflammatory cells to the fibroblasts and the synthesis of
metalloproteinases are calcium dependent. It has been hypothesized that the reduction in free calcium results in
impaired collagen resorption (Barclay et al., 1992). Another mechanism may be the production of collagenase.
This is supported by a study that demonstrated increased collagenase production by normal gingival fibroblasts
when exposed to nifedipine (Zebrowski et al., 1988).
Nifedipine has been shown to have indirect effects on components of the gingival tissues. The reduction
of free calcium by nifedipine can result in the prevention of phytohemagglutinin (PHA)-induced lymphocyte
proliferation, and the reduction of both lectin-induced increase of free cytosolic calcium and interleukin-2
secretion (Gelfand et al., 1986). Another indirect effect of nifedipine includes the production of higher levels of
active androgen metabolites by fibroblasts from patients with nifedipine-induced gingival overgrowth
(Sooriyamoorthy et al., 1990). Nifedipine at a physiological level may stimulate the production of interleukin-2
by T-lymphocytes, or the production of active androgen metabolites, and this could then result in the
proliferation and subsequent increase in collagen synthesis by fibroblasts (Nishikawa et al., 1991). Other indirect
effects of nifedipine include the increased synthesis of growth factors such as transforming growth factor- and
basic fibroblast growth factor. Both growth factors, their receptors, and heparan sulphate glycosaminoglycan
were increased in nifedipine-induced overgrowth tissue (Saito et al., 1996). The in vivo levels of interleukin-1
have been shown to be inversely proportional to the in vitro responsiveness of the fibroblasts from nifedipineinduced gingival overgrowth, which helps support the concept that nifedipine affects the metabolism of
fibroblasts (Henderson et al., 1997). Medullasin, a neutrophil elastase-like proteinase, was increased in
nifedipine-induced gingival overgrowth tissue. This enzyme may participate in the pathogenesis of the
overgrowth, possibly through host defence and immunoregulation, but the mechanism through which it acts is not
fully known (Kunimatsu et al., 1996). Together, it is evident that nifedipine may act indirectly to contribute to
the overgrowth tissue.
The presence of dental plaque and inflammation and its role in the pathogenesis of nifedipine-induced
gingival overgrowth is unclear (Marshall and Bartold, 1998). One study has reported that plaque is not related
to the presence of gingival overgrowth (Barclay et al., 1992). This is contrary to the findings of other studies and
case reports which demonstrate that plaque is a cofactor necessary for nifedipine-induced gingival overgrowth
(Ellis et al., 1999; Hancock and Swan 1992; Nery et al., 1995; Nishikawa et al., 1991). A study performed on

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pathogen-free rats showed that nifedipine induced gingival overgrowth occurred in the presence or absence of
inflammation and/or dental plaque, and that both factors could augment the effect of nifedipine on the gingiva
(Morisaki et al., 1993). One study has examined the microflora associated with nifedipine-induced gingival
overgrowth. It was determined that the percent and frequency of certain gram-positive and gram-negative rods
including Eubacterium alactolyticum, Capnocytophaga gingivalis, Capnocytophaga ochracea, Capnocytophaga
sputigena, and Fusobacterium nucleatum, were increased. It was further postulated that the combination of
impaired host response due to the medication, and the presence of enlarged gingiva, allowed for the development
of certain gram-negative anaerobic species (Nakou et al., 1998).

Cyclosporin-induced gingival overgrowth

Fibroblast heterogeneity and the direct and indirect effect of cyclosporin and its metabolites on the
fibroblasts are likely the main reasons for cyclosporin-induced gingival overgrowth (Marshall and Bartold,
1998).
Cyclosporin undergoes extensive hepatic metabolism, but it is not metabolized in one single pathway. The
major metabolic pathways include hydroxylation and N-demethylation of the amino-acids of the parent
compound. Of the 20 metabolites, 14 have been identified. The major metabolites, which can be determined by
high-pressure liquid chromatography (HPLC) include M17, M1, M18, and M21 (CPS, 1998; Garraffo, 1992;
Khoschsorur et al., 1998). There appears to be high individual variations with respect to resorption and
metabolization rates, but the recommended range of blood and plasma/serum levels of cyclosporin is between
100-400 ng/ml and 50-200 ng/ml, respectively (CPS, 1998; Seymour and Jacobs, 1992). The relationship
between plasma and/or salivary concentrations of cyclosporin has been reported to be a factor that is both
positively related (McGaw et al., 1987; Rostock et al., 1986; Seymour et al., 1987; Somacarrera et al, 1994), and
not related (Daley et al., 1986; Ross et al., 1989; Seymour and Smith, 1991) in the pathogenesis of cyclosporininduced gingival overgrowth. A study utilizing multiple sclerosis patients receiving cyclosporin demonstrated
that the odds ratio was 17.3 for having a cyclosporin blood level of >400 ng/ml and the incidence of overgrowth
(Hefti et al., 1994). The relationship between plasma/blood levels and overgrowth is unclear, and unfortunately,
most of the studies did not employ the use of high-pressure liquid chromatography to determine the plasma levels
(Marshall and Bartold., 1998). In addition to the dose of cyclosporin possibly having an influence on the
incidence and severity of the overgrowth, the duration of cyclosporin has been implicated as a factor that can
increase the chance of gingival overgrowth (Thomason et al., 1995).
Multiple in vitro studies have examined the effect of cyclosporin on fibroblast growth, as well as collagen
and proteoglycan synthesis. Both increased DNA synthesis and proliferation of fibroblasts (Bartold, 1989;
Mariotti et al., 1998; Willershausen-Zonnchen et al., 1992) and decreased DNA and reduction of total protein
production by fibroblasts (Barber et al., 1992) have been observed when exposed to cyclosporin. Collagen
synthesis has been reported to either decrease (Mariotti et al., 1998) or increase (Willershausen-Zonnchen et al.,
1992). Proteoglycan synthesis has been observed to either decrease (Barber et al., 1992; Willershausen-

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Zonnchen et al., 1992), remain unchanged (Bartold, 1989), or increase (Newell and Irwin, 1997). One
observation that appears to be consistent is the ability of cyclosporin to retain its ability to induce proliferative
activity despite the presence of lipopolysaccharide (Barber et al., 1992; Bartold, 1989). The disparity between
the in vitro studies may be due to fibroblast heterogeneity, and the use of only a limited number of fibroblast cell
lines. One in vitro study has demonstrated that fibroblasts derived from healthy gingiva showed heterogeneity in
basal levels of collagenase activity. When the fibroblasts were exposed to cyclosporin, the production of
collagenase was decreased in some strains, and was unchanged in other strains. This variation in collagenase
production was coincident with unchanged or increased production of tissue inhibitor of metalloproteinase
(TIMP). This study concluded that the heterogeneity of the collagenolytic response of the fibroblast strains may
explain why only some individuals exhibit cyclosporin-induced gingival overgrowth (Tipton et al., 1991). The
determination of human leukocyte antigen (HLA) phenotype as a risk factor for developing cyclosporin-induced
gingival overgrowth has been examined. It was determined that the HLA-B37 allele was statistically significant
as a risk factor for developing drug-induced overgrowth (Thomason et al., 1996b), and that the allele HLA-DR1
was significantly higher in patients who did not develop drug-induced overgrowth (Cebeci et al., 1996). These
results add further evidence to the concept of fibroblast heterogeneity.
The role of plaque and inflammation in the pathogenesis of cyclosporin-induced gingival overgrowth is
unclear (Marshall and Bartold, 1998). Various studies have reported that plaque and inflammation are factors
influencing the incidence and severity of the overgrowth (Daley et al., 1986; McGaw et al., 1987; Pernu et al.,
1992; Somacarrera et al., 1994; Wysocki et al., 1983). This has been supported by a study which demonstrated
that cyclosporin can concentrate locally in plaque (Niimi et al., 1990). Conversely, other studies have reported
that plaque and inflammation were not important determinants for gingival overgrowth (Seymour et al., 1987;
Seymour and Smith, 1991).
Another factor that may play a role in the pathogenesis of cyclosporin-induced gingival overgrowth is the
effect of cytokine expression. It has been shown that medication-induced overgrowth tissue contains
significantly higher levels of interleukin-6 (IL-6) mRNA when compared to control tissues (Williamson et al.,
1994). These findings were supported by the results of another study that showed that fibroblasts from
cyclosporin-induced gingival overgrowth tissue produced higher levels of IL-6 compared to controls when
cultured with cyclosporin in vitro (Myrillas et al., 1999). It was also demonstrated in the same study that
interleukin-1 was not significantly greater in the overgrown gingiva compared to the normal gingiva. Since IL1 induces connective tissue degradation by increasing the expression of collagenase and decreasing levels of
TIMP (Birkedal-Hansen, 1993), and IL-6 enhances connective tissue accumulation by increasing levels of TIMP
(Sato et al., 1990), it may be concluded that the altered expression of cytokines could play a critical role in the
pathogenesis of cyclosporin-induced gingival overgrowth (Myrillas et al., 1999). An in vivo study, which
determined the levels of IL-1, TNF-, and IL-6 in gingival crevicular fluid in patients with cyclosporin-induced
gingival overgrowth, reported that the levels of IL-1 were elevated, and the levels of IL-6 and TNF- were
unchanged. It was concluded that the cyclosporin therapy did not increase the levels of IL-1 and IL-6, rather,
the presence of gingival inflammation may be responsible for these elevated cytokine levels (Atilla and
Ktkler, 1998). Prostaglandin I2, which exerts an antiproliferative effect via cAMP-elevation, has been found

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to be decreased in gingival overgrowth tissue (Nell et al., 1996). In addition, immunolocalization studies have
demonstrated increased transforming growth factor- (TGF-) in the connective tissue papillae of cyclosporininduced gingival overgrowth samples (James et al., 1998). The authors isolated the fibroblasts from this tissue
and determined that increased matrix production by the fibroblasts occurred in response to TGF- (James et al.,
1998). The expression of both platelet-derived growth factor- (PDGF-) and its gene have been found to be
increased in cyclosporin-induced gingival overgrowth tissue (Iacopino et al., 1997; Nares et al., 1996; Plemons et
al., 1996). An in vivo study determined that the production of PDGF- was primarily by the macrophages, which
followed a non-uniform distribution throughout the gingiva (Nares et al., 1996). The production of cytokine
interleukin-1 by fibroblasts does not seem to increase when cultured with cyclosporin (Iacopino et al., 1997).
Cyclosporin appears to potentiate tumor necrosis factor- (TNF-) induced prostaglandin E2 (PGE2) formation
by gingival fibroblasts in a concentration dependent manner, which may play a role in the pathogenesis of
gingival overgrowth (Wondimu and Modeer, 1997). It is evident that cytokines may play a critical role in the
pathogenesis of cyclosporin-induced gingival overgrowth, but further studies may be required in order to form
definitive conclusions.

13. Formulate a treatment plan for Mr. Ien Kasvu. Include a plan for the
management of Mr. Kasvus chief complaint (bleeding overgrown gums; loose
denture; occasional sore gums).
Gingival overgrowth cannot be managed as an emergency treatment. However, oral
hygiene techniques can be revised as necessary. Also, the loose denture is not an
immediate concern. As well, denture stomatitis and denture hyperplasia underneath the
CUD cannot be eliminated without formulation of a comprehensive treatment plan. The
red/white lesions should be biopsied for definitive diagnosis before proceeding with
course of management.
NOTE:
Tutors should encourage the students to take this task home and discuss during the next
session about a treatment plan.
TUTORS: refer to List 2.
NOTE:
Students are expected to develop a treatment plan and treatment schedule for Mr. Kasvu.
This plan should involve at least the following:
1) Oral hygiene instructions (brushing the clefts with end-tufted or sulcabrush,
flossing, using Stimudent tooth picks where they fit the interproximal space)
2) Surgical removal of gingival overgrowth (gingivectomy); biopsy of oral lesions on
buccal mucosa
3) Referral for consultation with an oral surgeon re: pre-prosthodontic surgery
(removal of denture hyperplasia) and management of 48 (see below).

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4) New complete upper partial denture (or reline)

5) Maintenance program (see below)
14. Discuss the options for the management of impacted tooth 48. Is intentional
partial odontectomy an option?
The students should discuss the risks leaving 48 and the risks for extraction of 48. The
risks leaving 48 and observing could include at least the following: 1) route for bacteria to
penetrate tissue/bacteremia that could be a potential risk for loosing the transplant; 2)
Pericoronitis/chronic abscess; 3) Progression of bone loss distal to 47. The risks for 48
surgical removal are: 1) Temporary or permanent nerve damage; 2) Periodontal problems
after the extraction distal to 47 (deep pocket, increased tooth mobility, possibly
distalization of 47). Mr. Kasvu has had 48 exposed to oral cavity for a number of years
without having any episodes of pericoronitis. It is probably advisable to leave 48 and
observe and only extract if problems arise.

References:
Freedman GL. Intentional partial odontectomy: review of cases. Journal of Oral &
Maxillofacial Surgery. 55(5):524-6, 1997 May
Freedman GL. Intentional partial odontectomy: report of case. Journal of Oral &
Maxillofacial Surgery. 50(4):419-21, 1992
End of Tutorial 1.

1.
2.
3.
4.
5.
6.
7.
8.

Main learning issues from Tutorial 1:

Causes of gingival overgrowth
Histological features of gingival overgrowth
Pathological mechanisms of gingival overgrowth
Recognition of oral manifestations of systemic medications: lichenoid drug
reactions; gingival overgrowth
Management of immunocompromized patient
Assess the complexity of surgical removal of a third molar by clinical and
radiographic methods
Describe the surgical procedures available to improve the edentulous alveolar ridge
prior to denture construction
Relationship between systemic medication and gingival overgrowth

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Tutorial 2
Review learning issues from Tutorial 1.
Approximately 60 minutes should be spent on reviewing the last sessions learning
issues.
Your investigation has shown that Mr. Kasvus salivary production/flow was within
normal limits. However, Mr. Kasvu is still at risk for xerostomia and his saliva
production should continue to be monitored.
1. a) The incisional biopsy of the oral lesions on the buccal mucosa has been
performed. What information about Mr. Kasvu is important for the pathologist
to know and should have been provided on the biopsy form? Why?
Mr. Kasvus medical history of kidney transplant and multiple medications
(immunosuppressants and anti-hypertensives) should have been included as these factors
can affect the clinical and histologic presentation.
Please refer to Exhibit 3: photograph showing the histologic features of the biopsy
specimen from the buccal mucosa and the pathology report.
b) The pathologists report describes several histologic features that are also seen
in lichen planus and therefore, the pathologist has reported a diagnosis of
lichenoid (lichen-like) mucositis. What are the characteristic findings in lichen
planus?
Characteristic histologic findings of lichen planus:
Liquefaction of the basal layer of epithelial cells with possible near-total absence of
basal cells and destruction of the epithelial-connective tissue interface. Necrotic
keratinocytes are seen.
Intense infiltration of lymphocytes (T cells) in a band-like pattern within the upper
lamina propria parallel to the surface. There is also infiltration of lymphocytes into
the epithelium. Immunostaining demonstrates increased number of Langerhans cells
within the epithelium
White striae/plaques are due to hyper ortho/parakeratosis and occasional saw-tooth
pattern on rete ridges
Erythematous/atrophic sites are associated with thin/flattened epithelium. Erosions
may be seen due to progression of epithelial atrophy
NOTE: not all of the classic features of lichen planus may be seen at the same time.
Therefore, lesions with some of these characteristic features are designated as lichen-like
or lichenoid.
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1. c) As expected, the pathologist did not provide an etiology for the oral lesions.
However, you recall from a pathology lecture that graft-versus-host disease may
appear clinicially and histologically with features of lichen planus. You also
recall that Mr. Kasvu has had a kidney transplant. Is it possible that the oral
lesions on Mr. Kasvus buccal mucosa may actually be graft-versus host disease
(GVHD)?
No. GVHD is associated with bone marrow transplants and not solid organ transplants
such as kidney transplants.
d) What is the source of the immunocompetent cells responsible for causing GVHD?
Immunocompetent cells are derived from the donor marrow and they are reacting against
the host (the marrow recipients) tissues.
e) What may be the cause of Mr. Kasvus oral lichenoid lesions?
The specific etiology for lichen planus/lichenoid mucositis is not known but many factors
have been implicated including drugs. Any drug may cause a reaction including
lichenoid reactions. Drug-induced lichenoid reactions may occur within a short time after
introduction of the drug or reactions may be delayed for several years, complicating the
possibility of determining a cause-effect relationship. Even if a drug-associated etiology
is suspected, discontinuation of the suspected drug will not guarantee resolution of the
oral lichenoid changes. However, some drugs have a higher incidence of lichenoid
reactions than other drugs. Captopril is one drug that has an increased incidence of
lichenoid reactions but this data cannot be used to provide definitive etiology of Mr.
Kasvus lesions.
f) How may Mr. Kasvus lichenoid lesions be managed?
Avoid irritating factors such as spicy foods or acidic foods/beverages
Topical application of steroid ointment (eg Oracort) at time of discomfort and/or
increased erythema; be aware of increased risk of candidiasis; possible need for
adjunctive topical antifungal therapy
Topical application of Tantum for palliation of oral discomfort
Possible discontinuation of the suspected drug that induced the reaction; see above in
regards to limitations of this approach.
Mr. Ien Kasvu has a gingival overgrowth caused by cyclosporin and nifedipine. This
situation is further complicated with his inadequate oral hygiene. An oral surgeon has
recommended that denture hyperplasia should be reduced prior to fabrication of a new
maxillary complete upper denture but removal of 48 was not recommended (management
= observe)

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2. a) What is the surgical technique that is typically used to remove gingival

overgrowth?
The classical surgical technique is external bevel gingivectomy. The students should
study this technique from their textbook and be able to present it for the next session.
2.b) What is the difference between gingivectomy and gingivoplasty?
Gingivoplasty:
AAP: the surgical procedure by which gingiva is reshaped to create a normal, functional
form .
That is, the objective of gingivoplasty is to create physiologic gingival form rather than to
eliminate pockets.
Gingivectomy:
AAP: the excision of the soft tissue wall of the periodontal pocket. The incision forms
an external bevel or surface that is exposed to the oral cavity
The objective of gingivectomy is to eliminate pockets.
Gingivectomy and gingivoplasty are typically performed concurrently although for
teaching purposes, they are separate procedures. The two names reflect two different
objectives of the same procedure.
c) What types of pockets may be eliminated by gingivectomy?
Pseudopockets
Suprabony pockets

d) What are the basic prerequisites for gingivectomy?

the zone of gingiva must be wide enough so that the excision of part of the gingiva
will still leave a functionally adequate zone of keratinized attached gingiva
the underlying alveolar crest must be normal or nearly normal in form. If bone loss
has occurred, then the loss must be horizontal leaving a relatively regular crestal bone
form at a more apical level
there should be no infrabony (intra-alveolar) defects or pockets
e) Which of these criteria are present in Mr. Kasvus anterior mandibular
dentition?
All of the them.

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3. The surgical procedure of gingivectomy/gingivoplasty is planned for Mr. Kasvu.

a) What is the antibiotic regime recommended for Mr. Kasvu?
AHA recommendations starting with 2 grams amoxicillin po, one hour pre-op to
prevent bacteremia and wound infection
Guiding Question:
Should Mr. Kasvu receive additional antibiotics? Why? For how long?
Mr. Kasvu is immunocompromised with delayed healing response and possible
altered quantity/quality of saliva production. Moreover, gingivectomy procedure will
produce a wound that is open to the oral environment. Mr. Kasvu has increased risk
of post-operative infection and therefore, antibiotic coverage for at least 7 days postsurgery is recommended, eg. (Amoxicillin 500 mg tid for 7 days).
b) Does this antibiotic regime increase the risk of any other oral infections? How
should this risk be managed?
Yes, candidiasis. Antibiotics, immunosuppression and xerostomia are all risk factors for
candidiasis; Mr. Kasvu has all these risk factors. Prophylactic antifungals may be
considered but in the case of Mr. Kasvu, antifungals in addition to topical nystatin applied
under CUD, may be delayed until symptoms/signs support diagnosis of fungal infection
in addition to denture stomatitis. Chlorhexidine will be prescribed and this rinse will aid
in suppressing proliferation of candidiasis.
c) Review the list of Mr. Kasvus meds. Are there any other pre-operative
medications that should be considered for Mr. Kasvu?
Mr. Kasvu has been taking prednisone for a long time although his current dosage is only
5 mg every second day. There is a possibility of adrenal suppression/insufficiency in
which case, supplemental dose of prednisone should be provided pre-operatively.
Medical consultation may be prudent. General protocol for patients currently taking
corticosteroids includes double normal daily dose on day of procedure. If post-operative
pain is expected (as in case of Mr. Kasvu), then double daily dose on first post-operative
day as well is indicated. Good local anaesthesia and good post-operative pain control are
essential to reducing patient stress/anxiety. Blood pressure should be monitored prior to,
throughout and at end of surgical procedure.
d) What formulation(s) of local anesthetic is/are indicated for Mr. Kasvu? How will
the formulation of the LA affect the duration of local anaesthesia?
Minimal effective dose of vasoconstrictor should always be used. Mr. Kasvu has
hypertension that is managed with antihypertensive meds. Some of his medications have
possible side-effects of tachycardia, arrythmias, hyper/hypo tension. As well, surgery is a
stressful procedure for most patients and the increased production of endogenous
catecholamines will raise BP.

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Use of low concentration vasoconstrictor is indicated (eg 1:200,000 epinephrine versus

1:100,000 epinephrine). Plain LA (without vasoconstrictor) is not recommended for
surgical procedures due to the short duration of action which would require excessive use
of the LA (increased risk of toxicity).
One function of vasoconstrictor is to increase duration of LA (eg. pulpal anaesthesia with
citanest plain is 10 min with infiltration; pulpal anaesthesia with citanest forte [1:200,000
ep] is 60-90 minutes)
Use of increased concentrations of vasoconstrictor (eg 1:200,000, 1:100,000 or even
1:50,000 epinephrine) will NOT increase the duration of the anaesthetic effect but it will
increase the , effects. The duration of the anaesthesia is affected by the site of
injection (peripheral infiltration vs nerve block) and formulation of the anaesthetic
component (eg marcaine [bupivacaine] vs prilocaine [citanest])
e) In order to obtain good hemostasis, some surgeons and periodontists inject LA
directly around/into the surgical site. Concentrations of epinephrine 1:100,000 or
even 1:50,000 epinephrine are used. What are the benefits/risks of this approach?
Good hemostasis may be obtained by this approach but caution is required. Epinephrine
has both and effects.
- excessive -induced vasoconstriction can cause tissue necrosis, delayed
wound healing
- the rebound effect will result in vasodilation increased post-operative
bleeding
f) At what sites may LA be injected in order to obtain adequate anaesthesia for Mr.
Kasvus surgery?
Bilateral mental blocks with adjunctive infiltration into the anterior mucobuccal fold may
be used. This approach avoids the discomfort associated with bilateral inferior alveolar
blocks.
4. Upon completion of the gingivectomy procedure, how should the wound be
managed?
The site should be thoroughly irrigated with sterile saline in order to remove any debris.
Hemostasis must be present and periodontal dressing should be applied. Using wound
dressing (Coepak) will make the postoperative period more comfortable to the patient.
Dressing is almost always used after large gingivectomy. It may also help in preventing
postoperative bleeding. It does not, however, prevent bacteria from accumulating
underneath the dressing. It does not promote wound healing.
If hemostasis is a concern, then hemostatic agents such as microfibrillar collagen,
Surgicel may be applied first and then covered by the dressing. Histoacryl may be
applied but excessive application will delay wound healing.

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5. What oral hygiene measures should Mr. Kasvu employ during the postoperative
period?
Mr. Kasvu cannot brush his teeth at least for a week (covered by dressing). It is
recommended that he should use chlorhexidine rinse 30 sec, bid to prevent bacterial
colonization underneath the dressing. Chlorhexidine rinse should be used a minimum of
30 min after toothbrushing since sodium lauryl sulphate in toothpaste may interfere with
chlorhexidine action. A minimum of 4-6 weeks of rinsing is recommended to aid the
regular oral hygiene since the gingiva may be sensitive for brushing for up to two weeks
after surgery. Mr. Kasvu should start, however, brushing with a soft brush one week
(modified Bass method) after the operation. If the gingiva is too sensitive, new dressing
can be placed for another week, or Tantum (benzydamine HCL) solution maybe applied
topically for local analgesic/anti-inflammatory effects prior to performing oral hygiene (or
eating).
In any case, Mr. Kasvus healing is closely followed at 7 days, 3 weeks and then as
necessary. Interproximal hygiene (floss, proxabrush, stimudent depending upon
embrassure spaces) and use of rubber tip maybe started at 10-14 days.
6. What analgesics will you prescribe for Mr. Kasvu?
He should not take Aspirin for pain because it promotes bleeding due to platelet effects.
Acetominophen is the preferred analgesic versus NSAIDS as NSAIDs (including ASA)
carry increased risk of interaction with Mr. Kasvus prescribed meds (CSA, imuran,
prednisone, adalat, captopril) refer to List 1.
7. Describe the cellular and clinical events occurring beneath the periodontal
dressing. Begin the discussion with the immediate post-operative period when
the dressing is first placed and continue the discussion for 7 days when the
dressing is removed.
The students should be able to discuss the phases of wound healing (clot formation,
inflammation, reepithelialization, vascularization, granulation tissue formation, and
maturation). Text will be given to cover this in detail.
8. a) Several measures have been undertaken to prevent possible post-operative
complications for Mr. Kasvu. If an oral surgical or periodontal surgical
procedure was performed on a systemically-healthy adult patient instead of a
patient like Mr. Kasvu, can the risk of post-surgical complications be
eliminated?
No; risks can be reduced but not eliminated.

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b) Discuss the possible complications following oral surgical or periodontal surgical

procedures.
The students should list at least the following complications: bleeding, pain, infection. If
patient comes back after surgery, first thing is to remove the dressing and find out the
area of bleeding. In the case of an infection, dressing should also be removed to allow
drainage. Controlling bleeding after gingivectomy includes for example the following:
infiltration of local anesthetic with 1:50 000 epinephrine, compression,
electrocauterization, Histoacryl, and sometimes ligation by sutures (seldom in the case of
gingivectomy). Pain is managed by increasing dosage of pain medication or changing it to
stronger one. Infection is managed with antibiotics. In the case of Mr. Kasvu, he is
already on amoxicillin. If infection still arises, it is most likely caused by penicillin
resistant microorganism. In that case, Metronidazole 250 mg qid for 10 days should be
prescribed in addition to Amoxicillin. Alternatively, Amoxicillin should be stopped and
Clindamycin 150 mg qid with 300 mg initial dose should be started. Students should also
research the potential side effects of Clindamycin?
End of Tutorial 2

Main learning Issues for Tutorial 2:

1) Describe technique of gingivectomy
2) Explain main principles of wound healing
3) Management of postoperative oral hygiene
4) Management of postoperative complications

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Tutorial 3
Discuss Learning Issues identified in the last session. This will likely take about 60
minutes.
Discuss supportive periodontal therapy (maintenance) for Mr. Ien Kasvu
Treatment Plan:
Supportive periodontal therapy every 3 months containing:
- reinforcement of oral hygiene
- scaling and root planing
- selective polishing
Observe 48.
It is common that some rebound of the gingival overgrowth may occur in spite of efforts
to maintain good oral hygiene. It would help to change the medication but it is seldom a
possibility because of the underlying medical condition. It is helpful to know that the
dosage of cyclosporine is usually gradually decreased in patients with transplants and
lower concentrations are less likely to cause significant gingival overgrowth. Maintenance
therapy sometimes with the aid of chlorhexidine rinse will help to slow down the regrowth. Sometimes, it is necessary to repeat the surgical procedure to remove extra
growth that is of esthetic concern or prevents effective oral hygiene procedures.
Epilogue
Mr. Kasvu continues with the topical application of Oracort on as-needed basis for
occasional sensitivity of the buccal mucosa related to lichenoid mucositis. He uses the
Oroacort approximately 5-7 days per month. He has not experienced complication of
candidiasis and in general, the clinical presentation of the lichenoid mucositis is stable
with intermittent increase/decrease in degree of associated erythema and striation. Saliva
production/flow continues to be within normal limits.
Mr. Kasvus gingival overgrowth was successfully removed and managed by
gingivectomy surgical procedure at the Graduate Periodontics clinic. An oral surgeon
removed the floppy hyperplastic tissue from the ridge and the undergraduate student has
fabricated a new maxillary denture. The erythema (denture stomatitis) has disappeared
from the hard palate. The status of tooth 48 continued to observed and tooth 48 has
remained uncomplicated. During the first SPT visit, some tissue regrowth was noticed
evident but Mr. Kasvu is still able to use Stimudents in most interproximal spaces. No
additional gingival regrowth has occurred after six months and Mr. Kasvus gingival
conditions have remained stable for two years. He is pleased with the results and he
attends the Graduate Periodontics clinic on a regular basis for periodontal maintenance
therapy and ongoing review of oral lichenoid mucositis.

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