Secondary Amyloidosis Presenting as Oral Nodules

Amber Kiyani                                    BDS, MS, FAAOMP, Dip-ABOMP

Anam Zahid Kiani                             BDS, MSc

Uzair Luqman                                    BDS, FCPS, FFD RCS, FAOCMP

Secondary amyloidosis is a consequence of chronic inflammatory diseases that results in deposition of amyloid in organs disrupting its function. Oral involvement with this process is exceedingly rare. A 63-year-old Pakistani female with a history of rheumatoid arthritis and ankylosing spondylitis was seen in the Oral Medicine Clinics for painful oral nodules that were diagnosed as AA-type, or secondary amyloidosis, following an incisional biopsy. Similar deposits were identified in vital organs on subsequent examination by the patient’s physicians. Due to widespread systemic involvement, our patient died within 6-months of her diagnosis.
CONCLUSION: This case serves as a reminder that oral presentations may be the first identifiable signs of systemic diseases. It also emphasizes the importance of multidisciplinary clinical practice, and the lack of it in our country.
KEY WORDS: AA amyloidosis, secondary amyloidosis, oral amyloidosis.
HOW TO CITE: Kiyani A, Kiani AZ, Luqman U. Secondary amyloidosis presenting as oral nodules. J Pak Dent Assoc 2019; 28(4):204-206.
DOI: https://doi.org/10.25301/JPDA.284.204
Received: 28 April 2019, Accepted: 25 July 2019

INTRODUCTION

Secondary, or reactive amyloidosis is a type of systemic amyloidosis seen in patients with chronic inflammatory conditions, such as rheumatoid arthritis, inflammatory bowel disease, sarcoidosis, and tuberculosis. It results from proliferation and subsequent deposition of an acute-phase protein called serum amyloid A in tissues. Clinical features are usually slow to develop. The first manifestations are usually proteinuria and renal dysfunction. The severity of renal involvement determines prognosis of the patient. Liver and heart involvement may also be seen.1,2
Oral involvement with secondary amyloidosis is exceedingly rare. The most frequently affected site is the tongue. The protein deposition usually results in generalized or nodular macroglossia. More diffuse involvement of the oral cavity has also been reported as yellow nodules, or generalized ulceration.3,4
Here we present a case of a 63-year-old Pakistani female who was first diagnosed with secondary amyloidosis following a biopsy of her oral nodules, despite being under the care of multiple physicians for her systemic complaints. Our case emphasizes the need of multidisciplinary practice in Pakistan.

CASE REPORT

A 63-year-old Pakistani female presented to the Oral Medicine Clinics at Riphah International University with a complaint of painful oral nodules present for a “few” weeks. The ulcerated nodules, along with difficulty in swallowing were making food consumption difficult. The patient had lost at least 10 kilograms of weight. Her medical history was positive for rheumatoid arthritis and ankylosing spondylitis, both under treatment with variable doses of corticosteroids for twenty years. She had a recent diagnosis of renal failure that her doctors believed was secondary to her long-term corticosteroid use. She had recently begun complaining of bloody stool and voice changes.
Extraoral examination was unremarkable except for tag-like growths on both eyelids (figure 1). The patient said that they had been present for about two months. Intraoral examination revealed variablysized nodules on the tongue,
buccal and labial mucosae (figure 2,3). Some of the tongue nodules were ulcerated explaining the pain associated
with eating. No cervical lymphadenopathy or salivary gland enlargement was noted.

Figure 1: Nodular growths on the upper eyelid

Considerations in the differential diagnosis at this point included orofacial granulomatosis, oral Crohn’s disease and sarcoidosis. All three were ruled out following an incisional biopsy taken from a nodule on the buccal mucosa. It showed amorphous, eosinophilic deposits in the subepithelial and perivascular areas, suggestive of amyloid deposition

Figure 2: Nodular, ulcerated growths on lateral tongue

Figure 3: Nodular growths on buccal mucosa, site of incisional biopsy also visible.

(figure 4). The presence of the protein was confirmed by observing characteristic apple-green birefringence on Congo-red stained sections under polarized light. Immunohistochemical staining identified the protein type as AA thus allowing us to classify the disease as secondary amyloidosis.

Figure 4: Amorphous eosinophilic deposits in the subepithelial tissue.

The patient was referred to her nephrologist and gastroenterologist. The doctors confirmed deposition of amyloid in the kidney and the anal region. An ear-nosethroat specialist also identified amyloid deposits in the larynx. Due to the widespread involvement the patient was only offered palliative care. She did come back to us for debulking of the tongue and buccal mucosa to facilitate her eating. She died about 6 months after diagnosis.

DISCUSSION

Our case is an unfortunate account of a delayed diagnosis. Our patient’s kidney failure, phonation issues, cutaneous nodules, and gastrointestinal symptoms were all considered and treated as separate issues. By the time a definitive diagnosis was established, there was extensive multisystem involvement and only palliative care could be offered. This case underscores the importance of a multidisciplinary practice approach, and the lack of it in our country. Amyloidosis is a rare storage disease that results from an abnormal deposition of protein in single, or multiple
organs of the body. This gradual buildup of protein causes organ dysfunction and eventual failure.5 Common sites of
deposition include liver, spleen, kidney, heart and blood vessels.6
Amyloidosis is broadly classified into local and systemic types. Systemic amyloidosis is a more severe form of disease that is further categorized into primary, secondary, hemodialysis-associated and heredo-familial types on the basis of etiology. While the causes of hemodialysis-associated and heredo-familial types are straightforward, primary amyloidosis is often a consequence of plasma cell, or B cell neoplasms while secondary amyloidosis occurs in patients with a long-term diagnosis of chronic inflammatory conditions. Each one of these categories is identified by a unique protein type; primary by AL (light chain), AH (heavy chain) or AHL (heavy and light chain), secondary for AA, hemodialysis-associated by Aβ2 microglobulin and hereditary by ATTR.5
Oral manifestations of amyloidosis are rare. These include macroglossia and salivary gland hyperplasia. Secondary amyloidosis characteristically presents with tongue enlargement. This enlargement can be diffuse, or nodular like in our case. Other oral site, like buccal mucosa may also be involved.4,7,8
Diagnosis for oral amyloidosis is established with histopathologic examination. Viewing of sections stained with Congo-red under polarized light remains the gold standard for diagnosis.8
Although we were limited by our resources to classify the type of amyloidosis through immunohistochemical staining, more refined techniques involving biomarkers, and genetic sequencing are now available. These offer both diagnostic and prognostic values.5,6
Management of amyloidosis requires management of the underlying condition. In case of secondary amyloidosis that means treating the etiological chronic inflammator  condition through immunomodulators. This can slow the deposition of the amyloid protein and enhance longevity. Biomarker investigations have opened up avenues for definition of new therapeutic targets that prevent amyloid fibril deposition and encourage its clearance.5
In conclusion, our case is a reminder that oral involvement with secondary amyloidosis, while rare, may be the first identifiable sign of systemic involvement. It also highlights the consequences of a delayed diagnosis and the absence of multidisciplinary practice.

CONFLICT OF INTEREST

None declared

REFERENCES

  1. Lachmann HJ, Goodman HJ, Gilbertson JA, Gallimore JR, Sabin CA, Gillmore JD, et al. Natural history and outcome in systemic AA amyloidosis. New Eng J Medi. 2007;356:2361-71. https://doi.org/10.1056/NEJMoa070265
  2. Wechalekar AD, Gillmore JD, Hawkins PN. Systemic amyloidosis. Lancet. 2016;387(10038):2641-54. https://doi.org/10.1016/S0140-6736(15)01274-X
  3. Shahbaz A, Aziz K, Umair M, Malik ZR, Awan SI, Sachmechi I. Amyloidosis Presenting with Macroglossia. Cureus. 2018;10:e3185.
  4. Cengiz MI, Wang HL, Yildiz L. Oral involvement in a case of AA amyloidosis: a case report. J Medi Case
  5. Nuvolone M, Merlini G. Systemic amyloidosis: novel therapies and role of biomarkers. Nephrolog, dialysis, transplant: official publication of the Europ Dialysis and Transplant Association – Eur Renal Assoc. 2017;32:770-80.
  6. Bustamante JG, Brito D. Amyloidosis. StatPearls. Treasure Island (FL): StatPearls Publishing, StatPearls Publishing LLC.; 2019.
  7. Oruba Z, Kaczmarzyk T, Urbanczyk K, Jurczyszyn A, Fornagiel S, Galazka K, et al. Intraoral manifestation of systemic AL amyloidosis with unique microscopic presentation of intracellular amyloid deposition in striated muscles. Polish J path:2018;69:200-04. https://doi.org/10.5114/pjp.2018.76705
  8. Angiero F, Seramondi R, Magistro S, Crippa R, Benedicenti S, Rizzardi C, et al. Amyloid deposition in the tongue: clinical and histopathological profile. Anticancer Res. 2010;30:3009-14.

  1. Assistant Professor, Department of Oral Medicine, Riphah International University.
  2. Registrar, Department of Periodontology, Riphah International University.
  3. Consultant Oral Surgeon, Department of Oral and Maxillofacial Surgeon, KRL General Hospital.
    Corresponding author: “Dr. Amber Kiyani” < akiyani@gmail.com >

Secondary Amyloidosis Presenting as Oral Nodules

Amber Kiyani                                    BDS, MS, FAAOMP, Dip-ABOMP

Anam Zahid Kiani                             BDS, MSc

Uzair Luqman                                    BDS, FCPS, FFD RCS, FAOCMP

Secondary amyloidosis is a consequence of chronic inflammatory diseases that results in deposition of amyloid in organs disrupting its function. Oral involvement with this process is exceedingly rare. A 63-year-old Pakistani female with a history of rheumatoid arthritis and ankylosing spondylitis was seen in the Oral Medicine Clinics for painful oral nodules that were diagnosed as AA-type, or secondary amyloidosis, following an incisional biopsy. Similar deposits were identified in vital organs on subsequent examination by the patient’s physicians. Due to widespread systemic involvement, our patient died within 6-months of her diagnosis.
CONCLUSION: This case serves as a reminder that oral presentations may be the first identifiable signs of systemic diseases. It also emphasizes the importance of multidisciplinary clinical practice, and the lack of it in our country.
KEY WORDS: AA amyloidosis, secondary amyloidosis, oral amyloidosis.
HOW TO CITE: Kiyani A, Kiani AZ, Luqman U. Secondary amyloidosis presenting as oral nodules. J Pak Dent Assoc 2019; 28(4):204-206.
DOI: https://doi.org/10.25301/JPDA.284.204
Received: 28 April 2019, Accepted: 25 July 2019

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Management of Ectodermal Dysplasia with Tooth Supported Complete Overdentures: A Case Report

Muhammad Waseem Ullah Khan              BDS, FCPS

Momina Akram                                            BDS, FCPS

Sabiha Naeem                                              BDS

Ruksana Akram                                            BDS

Ectodermal dysplasia is a hereditary disease characterized by abnormal development of structures derived from embryonic ectoderm. Prosthetic rehabilitation of patients with ectodermal dysplasia is challenging. In this case report, a 19-year-old male was diagnosed with ectodermal dysplasia. His oral functions, esthetics and phonetics were successfully restored with upper and lower complete overdentures which greatly improve the psychological status of the patient.
KEY WORDS: Ectodermal dysplasia, overdentures, prosthodontic rehabilitation.
HOW TO CITE: Khan MWU, Akram M, Naeem S, Akram R. Management of ectodermal dysplasia with tooth supported complete overdentures: A case report. J Pak Dent Assoc 2019;28(4):201-203.
DOI: https://doi.org/10.25301/JPDA.284.201
Received: 29 March 2019, Accepted: 24 June 2019

INTRODUCTION

Ectodermal dysplasia comprises of a spectrum of inherited disorders due to abnormalities in the tissue derived from the embryonic ectoderm including Trichodysplasia, Hypodontia/Anodontia, Hypohidrosis/Anhydrosis and Onychodysplasia.1,2 More than 170 different nosologic groups of ectodermal dysplasia can be found in the literature but from a clinical standpoint, it can be divided in two major categories.2,3 Christ-SiemensTaurine Syndrome is the most common and classical form
which is genetically transmitted X-linked recessive trait and presents with hypodontia, hypohidrosis, hypotrichosis and particular faces.4
Orofacial manifestations of this syndrome include hypodontia, anodontia, hypo-plastic conical teeth, under development of alveolar ridges, loss of occlusal vertical dimension, prominent supraorbital ridges, frontal bossing, a depressed nasal bridge, protruded lips, hypotrichosis and dry oral mucosa.5 The other group is Clauson’s syndrome.
It is genetically autosomal dominant. It is the hidrotic form of this disease. Prominent feature of this category is unaffected sweat glands.4,6
Different management strategies for the patient of ectodermal dysplasia include removable partial dentures, resin bonded bridges, fixed partial dentures, complete dentures, overdentures and implants retained prosthesis. Choosing the best treatment option for the patient can significantly improve function, appearance and satisfaction.7,8
In this case report, we present the treatment option that is not only cost effective for the poor patient but also preserves and maintains the bone which in turn provides retention and stability in the given prosthesis.

CLINICAL REPORT

A 19-year-old male, a factory worker/laborer by profession, presented to the outdoor of Prosthodontics department at Punjab Dental Hospital, Lahore. His chief complaint was poor esthetics and compromised mastication. After thorough history and examination, a clinical diagnosis of hypohidrotic ectodermal dysplasia was made. He had properly formed finger and toe nails, normal skin, ear and respiratory system. Facial features showed senile appearance with frontal bossing, thin sparse hair on head, face and eyelashes, everted lips, depressed saddle of the nose, bulging at supraorbital area and depressed infraorbital area. Intra-oral examination revealed four permanent teeth (two central incisors and two canines) in the maxillary arch and one tooth (right lower canine) in the mandibular arch (Kennedy’s Class I in both arches). All teeth were conical in shape, tilted and spaced

Fig 1

(fig 1). The posterior teeth were not present in both arches so both arches were hypo-plastic, resorbed and under developed. Panoramic radiograph showed impacted left lower canine, atrophic under developed ridges with no other abnormalities (fig.2). Oral mucosa was thin but healthy. Patient’s parents, siblings and

Fig 2

Fig 3

relatives were normal not known to have a similar condition. Patient was otherwise medically and mentally healthy.
After the initial assessment, removable upper and lower complete overdentures with endodontic treatment of all
upper teeth were prescribed for the patient. Single visit root canal treatment of all upper teeth was done under
local anesthesia and dome shaped preparations for overdenture abutments were made. Amalgam fillings were used to restore the endodontically treated teeth. The right lower canine was also prepared in a dome shape to act as an overdenture abutment (fig3). During the preparation of lower canine, the pulp did not expose and signs of sensitivity were also not present, so endodontic treatment of this tooth was not considered necessary. Primary impressions with irreversible hydrocolloid and secondary impressions with eugenol free zinc oxide based impression material were made on the subsequent visits (fig 4).

Fig 4

Face-bow records, vertical and horizontal jaw relations were taken as per standard protocols. Articulation and tooth arrangement was done on a semi-adjustable articulator. Bilateral balanced occlusion was provided on average values on the semi adjustable articulator with edge-edge posterior occlusion on left side and cross bite on right side. Such an occlusion was required to keep the posteriors on the center of the ridge and compensates for the constricted maxillary arch and wider maxillary arch in the posterior region. Teeth try-in was done on the next visit (fig 5). The dentures were inserted after the necessary tissue surface and occlusal adjustments on the next appointment. The patient was instructed about the care of dentures and retained teeth. He was recommended a high fluoride paste to use twice daily

Fig 5

Fig 6

for his natural abutment teeth. The patient was kept under observation for 6 months. The patient was satisfied with the treatment. Fig 6 gives an idea of how drastically the esthetics were changed with properly made complete overdentures for this patient.

DISCUSSION

Ectodermal dysplasia is diagnosed intraorally by one of its main features that is hypodontia/anodontia.6 Sagittal and
vertical relationships of somatognathic system are severely compromised in the patients of ectodermal dysplasia.7 Most often patients present with class III inter-maxillary relationship, prominent chin, loss of vertical relationship.8 Prosthetic management of patients suffering from orphan diseases like ectodermal dysplasia requires a challenging
approach because of rarity of such syndromes.9
Multidisciplinary approach is recommended in such cases for treatment planning.5,10 Dental literature reports different prosthetic treatment options to the oral rehabilitation of patients with ectodermal dysplasia.2-5 Removable prostheses is the most common treatment of choice. The lack of fully developed alveolar ridges, xerostomia and under-developed maxillary tuberosities result in poor support, retention and stability in conventional complete denture. Conical anterior teeth pose problem to the removable partial denture stability but they are suitable to be used as abutments for overdentures.8
Osseo-integrated implants is one of the treatment options in patients with ectodermal dysplasia but adequate bone volume is important for the successful placement of implants, which is mostly lacking in these patients.5,7
In this case report, implant placement was not considered as treatment of choice because of atrophic under developed ridges and patient’s economic status. Overdenture was a suitable choice in this specific case as anterior atypical conical teeth used as abutments to compensate the drawbacks related to retention, stability and support in the case of removable partial or conventional complete dentures. Rehabilitation of patient’s function, esthetics and phonetics was up-to the mark and patient was truly satisfied with restored self-esteem.

CONCLUSION

Careful analysis of different phases of growth and development of craniofacial complex is required for oral rehabilitation of patients with ectodermal dysplasia. Toothsupported overdenture is most common and cost-effective treatment modality for the patients of ectodermal dysplasia. Care and maintenance of present natural teeth with adequate oral hygiene measures and topical fluoride prophylaxis is the key to the long-term success.

CONFLICT OF INTEREST

None declared

REFERENCES

  1. Dogan MS, Akbaba MH, Yavuz I, Tanik A, Aras A, Demirci F et al. Oral Rehabilitation of Patients with Ectodermal Dysplasia: Cases Series. Int J Health Sci 2016;4:59-8.
  2. Patidar C, Shigli A, Sharma DS, Kulkarni VK, Sharma S, Patidar C. Oral Rehabilitation of Hypohidrotic Ectodermal Dysplasia – A Case Report and Review. Ann. Prosthodont Resto Dent 2016;2:88-91
  3. Pandey R, Khatri A. Dental Management of Ectodermal Dysplasia: A Report of Two Cases. Journal homepage: www. nacd. in Indian J Dent Adv 2017;9:191-96. https://doi.org/10.5866/2017.9.10191
  4. Koyuncuoglu CZ, Metin S, Saylan I, Calisir K, Tuncer O, Kantarci A. Full-mouth rehabilitation of a patient with ectodermal dysplasia with dental implants. J Oral Implantol 2014. https://doi.org/10.1563/AAID-JOI-D-12-00072
  5. Nallanchakrava S. Oral rehabilitation of a patient with ectodermal dysplasia with prosthodontics treatment. Indian J Dermatol 2013;58:241. https://doi.org/10.4103/0019-5154.110851
  6. Hypodontia MA. Ectodermal dysplasia syndrome with cleft palate, hypodontia, metatarsus adductus and imperforate anus: a new syndrome? Pak Oral Dent J 2013;33.
  7. Dental management of persons with ectodermal dysplasia. Position statement. ACP 2016.
  8. Hekmatfar S, Jafari K, Meshki R, Badakhsh S. Dental management of ectodermal dysplasia: two clinical case reports. J Dent Res Dent Clin Dent Prospects 2012;6:108.
  9. Schnabl D, Grunert I, Schmuth M, Kapferer-Seebacher I. Prosthetic rehabilitation of patients with hypohidrotic ectodermal dysplasia: A systematic review. J Oral Rehabil 2018;45:555-70. https://doi.org/10.1111/joor.12638
  10. Alowairdhi AA. Prosthodontic management of children with ectodermal dysplasia: A literature review. Saudi Dent J 2019. https://doi.org/10.1016/j.sdentj.2019.02.036

  1. Assistant Professor, Department of Prosthodontics, de’Montmorency College of Dentistry Punjab Dental Hospital, Lahore.
  2. Assistant Professor, Department of Prosthodontics, de’Montmorency College of Dentistry Punjab Dental Hospital, Lahore.
  3. FCPS Post Graduate Resident, Department of Prosthodontics, de’Montmorency College of Dentistry Punjab Dental Hospital, Lahore.
  4. MDS Post Graduate Resident, Department of Prosthodontics, de’Montmorency College of Dentistry Punjab Dental Hospital, Lahore.
    Corresponding author: “Dr. Sabiha Naeem” < cute_sabi85@yahoo.com >

Management of Ectodermal Dysplasia with Tooth Supported Complete Overdentures: A Case Report

Muhammad Waseem Ullah Khan              BDS, FCPS

Momina Akram                                            BDS, FCPS

Sabiha Naeem                                              BDS

Ruksana Akram                                            BDS

Ectodermal dysplasia is a hereditary disease characterized by abnormal development of structures derived from embryonic ectoderm. Prosthetic rehabilitation of patients with ectodermal dysplasia is challenging. In this case report, a 19-year-old male was diagnosed with ectodermal dysplasia. His oral functions, esthetics and phonetics were successfully restored with upper and lower complete overdentures which greatly improve the psychological status of the patient.
KEY WORDS: Ectodermal dysplasia, overdentures, prosthodontic rehabilitation.
HOW TO CITE: Khan MWU, Akram M, Naeem S, Akram R. Management of ectodermal dysplasia with tooth supported complete overdentures: A case report. J Pak Dent Assoc 2019;28(4):201-203.
DOI: https://doi.org/10.25301/JPDA.284.201
Received: 29 March 2019, Accepted: 24 June 2019

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Salivary Biomarkers of Chronic Periodontitis

Naima Jabeen            BDS

Sarah Ghafoor           BDS, PhD

Chronic periodontitis is a slow progressing disease of oral tissue that causes inflammation and bleeding of gingiva. If it is untreated, it leads to periodontal pockets, loosening of teeth and ultimate tooth loss. Saliva is a hypertonic fluid present in the oral cavity that is now used as a diagnostic tool. Saliva contains water, organic and inorganic molecules that can act as biomarkers for systemic and oral diseases. Presence of these biomarkers in saliva can help in the early detection of chronic periodontitis disease for therapeutic purpose. This review summarizes the salivary biomarkers that can help in early detection and diagnosis of chronic periodontitis disease.
KEY WORDS: Chronic periodontitis, salivary biomarkers, systemic diseases, oral diseases.
HOW TO CITE: Jabeen N, Ghafoor S. Salivary biomarkers of chronic periodontitis. J Pak Dent Assoc 2019;28(4):197-200.
DOI: https://doi.org/10.25301/JPDA.284.197
Received: 21 November 2018, Accepted: 08 August 2019

INTRODUCTION

Saliva is a complex hypertonic solution which is an exudate from salivary acini, gingival crevicular fluid and oral mucosa. Major salivary glands include parotid, submandibular and sublingual glands which secrete approximately 90% of saliva and the rest 10% of saliva is produced by minor salivary glands.1
Saliva contains 99% of water and 1% consist of organic molecules and inorganic component (e.g., proteins, carbohydrates and lipids). A healthy person secretes 600ml of saliva in the whole day.2
The function of saliva is to maintain the oral cavity health by means of their antibacterial and antiviral activity. It also helps in lubrication, taste, digestion and provides tooth integrity and repair of oral mucosa3 (Figure 1).
“The term, biomarker, refers to measurable and quantifiable biological parameters than can serve as indicators for health and physiology-related assessments, such as pathogenic processes, environmental exposure, disease diagnosis and prognosis or pharmacologic responses to a therapeutic intervention”.4
According to the National Institutes of Health (NIH), a biomarker is a characteristic that is objectively measured and evaluated as an indicator of a normal biological process, pathogenic process, or pharmaceutical response to therapeutic intervention.5

BIOMARKERS IN SALIVA

In comparison to the blood sample collection, saliva

Figure 1: Physiological functions and active constituents of human saliva

collection is non invasive, patient compliant and convenient for clinician. Saliva consists of different types of hormones, enzymes, antibodies, antimicrobial components and cytokines .4
Saliva contains numerous defense proteins such as salivary immunoglobulins and salivary chaperokine 70kDa heat shock proteins (HSP70/HSPA), which are related to both innate and acquired immune system.6
The secretory immunoglobulin A (IgA) is the major salivary immunoglobulin that produces adherence of specific
microorganisms, avoiding their cohesion to oral mucosa and making clusters. Recent study has shown that saliva also contains surfactant proteins, which are the members of the immune defense system.7
Saliva consists of many systemic markers such as antibodies, interleukins and neoplastic markers which can be used in diagnosis and analyzing various systemic diseases such as diabetes mellitus8, cancers such as breast cancer9, oral diseases such as oral squamous cell carcinoma10 and cardiovascular diseases such as acute myocardial infarction.11
This can help in the early detection and progression of disease and monitoring of the therapeutic drugs.12 Salivary
biomarkers of systemic and oral diseases are listed in table 1.

SALIVARY BIOMARKERS IN CHRONIC PERIODONTITIS

Chronic periodontitis is a slow progressing inflammatory disease which can lead to the destruction of the periodontal ligament, alveolar bone loss, pocket formation and gingival recession.13,14 It mostly occurs in adults. Clinical features include plaque and calculus deposition, when untreated leads to inflammation and bleeding of gingiva, periodontal pockets and periodontal tissue attachment loss. It is classified according to the clinical conditions as localized and generalized periodontitis.15,16 It is also categorized by severity of periodontal tissue breakdown that includes mild, moderate and severe chronic periodontitis. It determines the health of the periodontal tissue that can be recorded as clinical attachment level (CAL) and that is measured with a periodontal probe. CAL is the distance between cementoenamel junction (CEJ) and the base of the periodontal pocket.17 Various local and systemic factors are associated with chronic periodontitis such as poor oral hygiene, poor nutrition, malocclusion, overhanging restorations, smoking, obesity, alcohol consumption, psychological factors and metabolic disorders.13
Pathogenesis of chronic periodontitis involved the gram negative anaerobic bacteria such as Porphyromonas gingivalis, Bacteroides forsythus, and Prevotella intermedia.18,19 These microorganisms present in calculus, may exert pathogenic effect either directly by tissue destruction or indirectly by activating host response. Substances released from bacteria reach gingival tissue and results in chronic inflammation that leads to activation of B-lymphocytes, T-lymphocytes, neutrophils, monocytes, and macrophages that release inflammatory mediators such as chemokines, proteolytic enzymes, and cytokines. Therefore, local variation and damage of host tissue may manifest as periodontal disease.13
Many molecules have been analysed as potential biomarkers for periodontal diseases such as enzymes {for example matrix metalloproteinases-8 (MMP-8)}, cytokines {for example interleukin-1β (IL-1β)}, receptors (for example collectins) and other proteins (for example high sensitive c-reactive protein (hs-CRP) and osteocalcin). These biomarkers can also be present in several biological fluids (such as serum, blood, plasma and gingival crevicular fluids) in higher concentration in compare with healthy individuals. d High sensitivity c-reactive protein (hs-CRP) is member of an innate immune system, it has higher levels in serum of chronic periodontitis patients and used as a systemic biomarker.20 Osteocalcin is non-collagenous calcium binding protein present in mineralized tissue which take part in bone destruction. Salivary levels of osteocalcin are raised in chronic periodontitis patients in compare with healthy individuals.21
Anaerobic gram negative bacteria such as Prevotella porphyromonas (mainly P.gingivalis) and Tannerella forsythia in saliva have pathogenic potential in chronic periodontitis. These organisms contain 3-hydroxy fatty acid (3-OH-FA). 3-OH FA analysis in saliva help in determining the early detection of chronic periodontitis.22 There is the
number of enzymes that are released by inflammatory cells during the pathophysiology of chronic periodontitis which caused the connective tissue degradation and bone loss. Matrix metalloproteinase (MMP-8), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) are some of the enzymes that are used as a salivary biomarker of chronic periodontitis.23
Oral epithelial cells secretes a large number of cytokines such as granulocyte-macrophage colony stimulating factor (m-CSF), interleukin-1β (IL-1β), interferon- (IFN- ) and tumour necrosis factor-α (TNF-α) which can cause inflammation and destruction of periodontal tissue. The levels of these cytokines in saliva are influenced by the salivary mucins whose presence can limit the absolute concentration of these cytokines for detection.24,25 Salivary nitric oxide (NO) metabolite and toll- like receptors (TLR-2 and TLR-4) are used as biomarkers which are predictive indicator of periodontal inflammatory condition.26,27 Protein carbonyl (PO) causes oxidative damage may leads to decline of protein function. Higher levels of PO and salivary cortisol present in Chronic periodontitis are used as salivary biomarkers.28,29

CONCLUSION

The early detection or diagnosis of chronic periodontitis can resist the disease progression. This can positively affect the health of the individual as untreated chronic periodontitis causes pain, swelling and bleeding of gingiva, loosening of teeth and tooth loss. Numerous salivary biomarkers of chronic periodontitis can help in the early diagnosis and monitoring of this disease. Furthermore, there are still chances of unidentified biomarkers in the saliva of chronic periodontitis that can be explored.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

FUNDING

Nothing to declare.

ACKNOWLEDGEMENTS

The author like to thank the Higher Education Commission of Pakistan (HEC) for providing electronic library access to the University through which valuable information for completing this review paper was possible.

REFERENCES

  1. Berkovitz BK, Holland GR, Moxham BJ. Oral Anatomy, Histology and Embryology E-Book: Elsevier Health
  2.  Zhang C-Z, Cheng X-Q, Li J-Y, Zhang P, Yi P, Xu X, et al. Saliva in the diagnosis of diseases. Int J Oral Sci. 2016;8:133. https://doi.org/10.1038/ijos.2016.38
  3. Castagnola M, Cabras T, Vitali A, Sanna MT, Messana I. Biotechnological implications of the salivary proteome. Trends Biotechnol. 2011;29:409-18. https://doi.org/10.1016/j.tibtech.2011.04.002
  4. Spielmann N, Wong D. Saliva: diagnostics and therapeutic perspectives. Oral Dis. 2011;17:345-54. https://doi.org/10.1111/j.1601-0825.2010.01773.x
  5. Yakob M, Fuentes L, Wang MB, Abemayor E, Wong DTW. Salivary biomarkers for detection of oral squamous cell carcinoma – current state and recent advances. Curr Oral Health Rep. 2014;1:133-41. https://doi.org/10.1007/s40496-014-0014-y
  6. Fábián TK, Hermann P, Beck A, Fejérdy P, Fábián G. Salivary defense proteins: their network and role in innate and acquired oral immunity. Int J Mol Sci. 2012;13:4295-320. https://doi.org/10.3390/ijms13044295
  7. Schicht M, Stengl C, Sel S, Heinemann F, Gotz W, Petschelt A, et al. The distribution of human surfactant proteins within the oral cavity and their role during infectious diseases of the gingiva. Ann Anat. 2015;199:92-7. https://doi.org/10.1016/j.aanat.2014.05.040
  8. Abd-Elraheem SE, El saeed Am, Mansour HH. Salivary changes in type 2 diabetic patients. Diabetes Metab Syndr. 2017;11:S637-S41. https://doi.org/10.1016/j.dsx.2017.04.018
  9. Porto-Mascarenhas EC, Assad DX, Chardin H, Gozal D, De Luca Canto G, Acevedo AC, et al. Salivary biomarkers in the diagnosis of breast cancer: A review. Crit Rev Oncol Hematol. 2017;110:62-73. https://doi.org/10.1016/j.critrevonc.2016.12.009
  10. Ishikawa S, Sugimoto M, Kitabatake K, Sugano A, Nakamura M, Kaneko M, et al. Identification of salivary metabolomic biomarkers for oral cancer screening. Sci Rep. 2016;6:31520. https://doi.org/10.1038/srep31520
  11. Abdul Rehman S, Khurshid Z, Hussain Niazi F, Naseem M, Al Waddani H, Sahibzada HA, et al. Role of Salivary Biomarkers in Detection of Cardiovascular Diseases (CVD). Proteomes. 2017;5:21. https://doi.org/10.3390/proteomes5030021
  12. Chojnowska S, Baran T, Wilinska I, Sienicka P, Cabaj-Wiater I, Knas M. Human saliva as a diagnostic material. Adv Med Sc. 2018;63:185-91. https://doi.org/10.1016/j.advms.2017.11.002
  13. Batool H, Afzal N, Shahzad F, Kashif M. Relationship between rheumatoid arthritis and chronic periodontitis. J Med Radiol Pathol Surg. 2016;2:11-4. https://doi.org/10.15713/ins.jmrps.50
  14. Javed F, Ahmed HB, Mehmood A, Mikami T, Malmstrom H, Romanos GE. Self-perceived oral health and periodontal parameters in chronic periodontitis patients with and without rheumatoid arthritis. J. Investig Clin Dent. 2016;7:53-8. https://doi.org/10.1111/jicd.12113
  15. Armitage GC, Cullinan MP. Comparison of the clinical features of chronic and aggressive periodontitis. Periodontol 2000. 2010;53:12- 27. https://doi.org/10.1111/j.1600-0757.2010.00353.x
  16. Bingham III CO, Moni M. Periodontal disease and rheumatoid arthritis: the evidence accumulates for complex pathobiologic interactions. Curr Opin Rheumatol. 2013;25:345. https://doi.org/10.1097/BOR.0b013e32835fb8ec
  17. Highfield J. Diagnosis and classification of periodontal disease. Aust Dent J. 2009;54(s1):S11-S26. https://doi.org/10.1111/j.1834-7819.2009.01140.x
  18. Detert J, Pischon N, Burmester GR, Buttgereit F. The association between rheumatoid arthritis and periodontal disease. Arthritis Res Ther. 2010;12:218. https://doi.org/10.1186/ar3106
  19. Farquharson D, Butcher J, Culshaw S. Periodontitis, Porphyromonas, and the pathogenesis of rheumatoid arthritis. Mucosal Immunol. 2012;5:112-20. https://doi.org/10.1038/mi.2011.66
  20. Stathopoulou PG, Buduneli N, Kinane DF. Systemic Biomarkers for Periodontitis. Curr Oral Health Rep. 2015;2:218-26. https://doi.org/10.1007/s40496-015-0072-9
  21. Miricescu D, Totan A, Calenic B, Mocanu B, Didilescu A, Mohora M, et al. Salivary biomarkers: Relationship between oxidative stress and alveolar bone loss in chronic periodontitis. Acta Odontol Scand. 2014;72:42-7. https://doi.org/10.3109/00016357.2013.795659
  22. Ferrando R, Szponar B, Sánchez A, Larsson L, Valero-Guillén PL. 3-Hydroxy fatty acids in saliva as diagnostic markers in chronic periodontitis. J Microbiol Methods. 2005;62:285-91. https://doi.org/10.1016/j.mimet.2005.04.014
  23. Nomura Y, Shimada Y, Hanada N, Numabe Y, Kamoi K, Sato T, et al. Salivary biomarkers for predicting the progression of chronic periodontitis. Arch. Oral Biol. 2012;57:413-20. https://doi.org/10.1016/j.archoralbio.2011.09.011
  24. Tobón-Arroyave SI, Jaramillo-González PE, Isaza-Guzmán DM. Correlation between salivary IL-1ß levels and periodontal clinical status. Arch. Oral Biol. 2008;53:346-52.https://doi.org/10.1016/j.archoralbio.2007.11.005
  25. Teles RP, Likhari V, Socransky SS, Haffajee AD. Salivary cytokine levels in subjects with chronic periodontitis and in periodontally healthy individuals: a cross-sectional study. J Periodont Res. 2009;44:411-17. https://doi.org/10.1111/j.1600-0765.2008.01119.x
  26. Scarel-Caminaga RM, Cera FF, Pigossi SC, Finoti LS, Kim YJ, Viana AC, et al. Inducible Nitric Oxide Synthase Polymorphisms and Nitric Oxide Levels in Individuals with Chronic Periodontitis. Int J Mol Sci. 2017;18:1128. https://doi.org/10.3390/ijms18061128
  27. Al Qallaf H, Hamada Y, Blanchard S, Shin D, Gregory R, Srinivasan M. Differential profiles of soluble and cellular toll like receptor (TLR)- 2 and 4 in chronic periodontitis. PloS one. 2018;13:e0200231-e. https://doi.org/10.1371/journal.pone.0200231
  28. Baltacioglu E, Sukuroglu E. Protein carbonyl levels in serum, saliva and gingival crevicular fluid in patients with chronic and aggressive periodontitis. Saudi Dent J. 2018;31:23-30. https://doi.org/10.1016/j.sdentj.2018.09.003
  29. Botelho J, Machado V, Mascarenhas P, Rua J, Alves R, Cavacas MA, et al. Stress, salivary cortisol and periodontitis: A systematic review and meta-analysis of observational studies. Arch Oral Biol. 2018;96:58-65. https://doi.org/10.1016/j.archoralbio.2018.08.016

  1. M.Phil Trainee, Department of Oral Biology, University of Health Sciences, Lahore.
  2. Assistant Professor, Department of Oral Biology, University of Health Sciences, Lahore.
    Corresponding author: “Dr. Sarah Ghafoor” < sarahghafoor@uhs.edu.pk >

Salivary Biomarkers of Chronic Periodontitis

Naima Jabeen            BDS

Sarah Ghafoor           BDS, PhD

Chronic periodontitis is a slow progressing disease of oral tissue that causes inflammation and bleeding of gingiva. If it is untreated, it leads to periodontal pockets, loosening of teeth and ultimate tooth loss. Saliva is a hypertonic fluid present in the oral cavity that is now used as a diagnostic tool. Saliva contains water, organic and inorganic molecules that can act as biomarkers for systemic and oral diseases. Presence of these biomarkers in saliva can help in the early detection of chronic periodontitis disease for therapeutic purpose. This review summarizes the salivary biomarkers that can help in early detection and diagnosis of chronic periodontitis disease.
KEY WORDS: Chronic periodontitis, salivary biomarkers, systemic diseases, oral diseases.
HOW TO CITE: Jabeen N, Ghafoor S. Salivary biomarkers of chronic periodontitis. J Pak Dent Assoc 2019;28(4):197-200.
DOI: https://doi.org/10.25301/JPDA.284.197
Received: 21 November 2018, Accepted: 08 August 2019

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The Survey of the Knowledge of Dry Socket and Management Among Dental Practitioners; Still Controversy?

Naveed Khawaja           BDS, MCPS, DOMS, MSc-OPath (UK), FADI

Kauser Parveen            BDS, MCPS

Abdullah Almotreb       BDS

Rashed Tashkandi        BDS

OBJECTIVE: Dry Socket (DS) is one of the complications following tooth extraction, reported usually 2-4 days postoperatively with moderate to severe pain. The concept of Dry Socket is not clear and there is disagreement among dental practitioners about diagnosis and management. The objective of this survey was to evaluate the knowledge of dry socket and its treatment among General Practitioners.
METHODOLOGY: One hundred and twenty-nine structured questionnaires were distributed among Dental Practitioners (DP) of Riyadh city with 78% response rate. This study was composed of two part; first about knowledge and second regarding treatment options. Data was collected, tabulated and analyzed using updated SPSS version 22.
RESULTS: According to the results, 75.2% (n=76) practitioners agreed that dry socket is dislodgment of clot in socket, and 20.8% (n=21) agreed that dry socket could be due to contamination of socket. Moreover, 32.7% (n=33) dental practitioners claimed that dry socket patients experienced discomfort symptom but most of the dentists 75.2%n (n=76) reported acute and stabbing pain in dry socket.
CONCLUSION: The overall knowledge of diagnosis and treatment of general practitioners was adequate.
KEY WORDS: Dry Socket; Knowledge; Dental Practitioner; Treatment
HOW TO CITE: Khawaja N, Parveen K, Almotreb A, Tashkandi R. The survey of the knowledge of dry socket and management among dental practitioners; still controversy?. J Pak Dent Assoc 2019;28(4):192-196.
DOI: https://doi.org/10.25301/JPDA.284.192
Received: 21 December 2018, Accepted: 04 September 2019

INTRODUCTION

Exodontia is a common procedure in Dentistry. Dry Socket (DS) is one of the delayed post-extraction complication, reported usually 2-4 days postoperatively with moderate to severe pain with the incidence of 0.5-5% in routine extractions.1-2 The name dry socket is used because blood clot is lost and covered by a green-grayish membrane. This term was first used in 1896 by Crawford.3
Since then, other terms have been used to describe dry socket: localized osteitis, alveolar osteitis (AO), fibrinolytic alveolitis, alveolitis sicca dolorosa, and localized osteomyelitis.4 Dry socket is dislodgment of clot with exposed intrasocket bone (denuded bone) as acute painful complication arising 72 hours postoperatively.5,6 Most of published data states that the incidence of dry socket is 1-5% for all routine dental extractions and up to 40% for impacted mandibular third molars.7-11 The incidence of dry socket is higher in the mandible than maxillae12, occurring up to 10 times more often for mandibular molars compared with maxillary molars because of dense bone.13 Clinically dry socket is characterized by severe throbbing pain, marked halitosis, foul odor, and greyish look.
Several theories have been documented on the etiology of dry socket including bacterial infection, trauma, and biochemical agents.9
According to one theory, there is increased fibrinolytic activity and activation of plasminogen to plasmin in the presence of tissue activators in dry sockets.14 This fibrinolytic activity is thought to affect the integrity of the post-extraction blood clot. 2 Microscopically, dry socket is characterized by the presence of inflammatory cellular infiltrate, with numerous phagocytes and giant cells in the remaining clot, associated with presence of bacteria and necrosis of the lamina dura.15
Birn reported that the inflammatory process can extend to the medullar spaces and sometimes the periosteum,
resulting in connective tissue inflammation of the contiguous mucosa, with microscopic features typically of osteomyelitis.16 Degradation of the blood clot in association with dissolution of erythrocytes and fibrinolysis, deposits of hemosiderin, and the absence of organized granulation tissue has been described in histopathologic investigation of dry socket.15
The treatment of Dry Socket depends on each professional’s clinical experience mainly due to its complex etiology, although many authors have published research on the management of dry socket. Therefore, the concept of management mainly depends upon diagnosis which is mostly conservative but confusion still exist among practitioners in approach to diagnosis and treatment.17 Ideally recommended treatment is to irrigate the socket to
debride and place ZOE / Alveogyl dressing for pain and inflammation.17
The objective of this study was to evaluate the knowledge of dry socket and its management among dental practitioners in Riyadh.

METHODOLOGY

One hundred and twenty-nine (129) structured questionnaires were distributed consisting of fourteen questions among Dental Practitioners (DP) of Riyadh city. One hundred and one (n=101; 78%) GP responded about Knowledge of Dry Socket and its management. Only completely filled questionnaires were included in final analysis.
First part of questionnaires was related to features / diagnosis and second part was the management of Dry Socket.
Data was tabulated and statistical analysis was evaluated by SPSS version 22. Frequency and percentage was calculated for study variables.

RESULTS

One hundred and one (78%) out of 129 dental general practitioners responded the self-administrated questionnaire.
Among them, Ninety one (90.1%) were male and Ten (9.9%) were female dental practitioners. Ninety-four (93.1%) practitioners were graduates by qualification and Seven (6.9%) were postgraduates dentist. The survey for was divided into two part; knowledge of dry socket and its management.

Knowledge of Dry Socket

Table 1: Knowledge of dry socket among dental general practitioners Table 1 Shows the responses of study participants about the knowledge of dry socket among dental practitioners. In the results of this study, Seventy-Six (75.2%) practitioners agreed that dry socket is dislodgment of clot in socket, and on the other hand Twenty-one (20.8%) also agreed that dry socket could be due to contamination of socket. Moreover, thirtythree (32.7%) dental practitioners claimed that dry socket patients may have discomfort symptom. Most of the dentists (n=76, 75.2%) reported acute and stabbing pain as symptom of dry socket whereas Fourteen (13.9%) dentist responded dull, continuous pain.
Fifty-five (54.4%) reported pain was after of extraction 72 hours. Twenty-nine (28.7%) reported 24 hours, six (5.9%) reported immediately and Eleven (10.9%) dentists did not respond. Proportion t-test were significant. Analysis showed significant results.
Regarding complicating factor, sixty-nine (68.3%) dentists were of view that dry socket is mainly due to surgical procedure. A total of Ninety-four (93.1%) dental practitioners reported diagnosing dry socket on basis of clinical examination and symptoms whereas Four (4%) diagnosed on symptoms only.

Knowledge of Dry Socket management

Table 2: Concept of management of dry socket among dental general practitioners

Table 2 Depicts about knowledge of management of dry sockets. Seventy-nine (78.2%) dentists claimed that dry socket can be managed by saline irrigation (p 0.000) whereas Fifty-three (52.5%) agreed that dry socket could be treated by intra-socket sedative dressing (p 0.619), however most of practitioner favored irrigation as well as intra-socket sedative dressing (p 0.000). Eight (7.9%) dentists suggested to leave the wound as such for healing without any application and Thirty-six (35.6%) suggested antibiotic intake only to manage dry socket (p 0.004).
On the other hand, sixty-five (64.4%) were in the favor of curettage (p 0.003) and Six (5.9%) suggested to manipulate aggressively to use drill. Ninety-two (91.2%) dentists suggested that no surgery was needed to manage dry socket (p 0.000) and 62 (61.4%) dentists did not suggest antibiotic in the cases of dry socket (p 0.017).
Moreover, sixty-five (64.4%) dental practitioners suggested non-steroidal anti-inflammatory drugs to reduce pain and Twenty-three (22.8%) suggested paracetamol as painkiller.

DISCUSSION

In this study, Seventy Six (75.2%) practitioners agreed that dry socket is dislodgment of clot in socket, 21 (20.8%) also agreed that dry socket could be due to contamination of socket. Most of the dentists 76 (75.2%) documented acute and stabbing pain in dry socket whereas 14 (13.9%) dentist reported that patients with dry sockets experience pain. Overall, dentist knowledge about diagnosis of dry socket showed statistically significant results (< 0.000). On the other hand, 79% agree on saline irrigation and 53% of dentists rely on intra-socket sedative dressing. Interestingly, 92 (91.2%) dentists do not agree that surgery is required to manage dry socket which was significant (p 0.000). Dry socket may present as a challenge for the dentists and specialist alike.
The exact etiology and mechanism of dry socket are not known but several factors have been associated. Careful analysis into pathophysiology of dry socket stated that poor oral hygiene, vasoconstrictors and reduced blood supply are an important factors but reports have emphasized on trauma from difficult extractions causing fibrinolysis and release of pain inducing chemical substances.18 One recent study 19 emphasized need to educate patients properly for postextraction instructions and significant association of compliance with instructions and the reduced incidence of dry socket (p 0.015). A study conducted by Birn et al 20 with similar survey on the internship dentist’s knowledge
about dry socket documented results on the causes and reported that gender, oral contraceptives and antibiotics effect on dry socket.
In present study, seventy six percent reported dislodgment of clot with acute stabbing pain with-in 72 hours and sixty nine reported that dry socket is due to surgical procedure. These results show that the study respondents had adequate knowledge about dry socket. One recent similar survey21 in 2017 reported similar observations and concluded that the study participants had an adequate knowledge of diagnosis of dry socket with symptoms.
Studies have already documented that oral contraceptives were associated with a significant increase in the frequency of dry socket after extraction of mandibular third molars.
The probability of dry socket increases with the estrogen that has fibrinolytic action. Catellini JE et al22 in 1980 documented the risk of dry socket associated with oral contraceptives can be minimized by performing extractions during days 23 through 28 of the tablet cycle. Ogunlewe MO et al in 201023 concluded that females (63.2%) have more incidence of dry socket as compared to males, reasons may be hormonal coupled with use of contraceptives. In this study, we did not include questions on contraceptive therapy and therefore is a limitation of our study.
Many options of management discussed in literatures include curettage and irrigation, LLLT (low level laser therapy), irrigation and packing with zinc oxide eugenol / iodoform paste, alvogyl and plasma rich in growth factors in remission of pain and alveolar mucosa healing. 24 Few studies are published on different treatment options and preventive measures to control its occurrence. A systemic review study in 201525 illustrated that the dry socket is one of the most common post-extraction complications in dental practice. One study26 used 2% lidocaine jelly in a prospective double-blind study of 30 adult patients diagnosed with dry socket and found that the experimental group had significantly lower pain perception immediately and up to 60 min after irrigation than in those sockets that had been treated with placebo. No side effects due to topical lidocaine use were found. However, many other studies documented reduction of incidence of dry socket using pre-operative measures like chlorhexidine, antibiotic (local and systemic), metronidazole, smoking cessation and many other measures. 27-33
In this study, 53% believed on intra-socket dressing with sedative / pain killer without any surgical intervention. On the other hand, more than 90% practitioners did not agree on surgical approach and aggressive manipulation of socket but 64.4 % were in favor of curettage which is really a controversy and debatable issue. However, curettage is not recommended due to the induction of more pain. Curettage involves administration of anesthesia, surgical debridement of socket, and primary closure by advancement flap. Turner 9 stated that curettage and removal of granulation tissue resulted in fewer visits than zinc oxide eugenol or iodoform gauze with eugenol techniquesmoking cessation and many other measures. 17 However there is no granulation tissue in typical dry socket.
Controversy is still going on among some practitioner in this study regarding diagnosis and management. Recommendation is only to debride the socket with saline and pack with sedative dressing for 48 hours. Many textbooks explained dry socket and its treatment but Kruger34 reported that practitioners still rely on intra-socket curettage. There is a commercial dressing available (Alveogyl, Iodoform+Butylpara-minobanzoate) for dry socket
management, few fibers can be placed intra-socket after irrigation, without need for removal.35 Proper teaching of knowledge of this complication should be an important which sometimes comes across in routine dental practice. However careful in managment after proper diagnosis is very important clinically. In future, many other important aspects related to occurrence of dry socket can be considered.

CONCLUSION

The knowledge of Dry Socket and its diagnosis / treatment for general practitioners is an important; one should know baseline of dry socket to treat. However, certain aspects of diagnosis and management is misunderstood.

CONFLICT OF INTEREST

None declared

REFERENCES

  1. Daly B, Sharif MO, Newton T, Jones K, Worthington HV. “Local interventions for the management of alveolar osteitis (dry socket)”. Cochrane Database of Systematic Reviews 2012. https://doi.org/10.1002/14651858.CD006968.pub2
  2. Soames JV; Southam JC. Oral pathology 4th ed. Oxford University Press. Oxford medical publication (1999) 296-98.
  3. Crawford JY. Dry socket after extraction. Dent Cosmos 1896; 38: 929-31.
  4. Awang MN. The aetiology of dry socket: a review. Int Dent J. 1989; 39:236-40.
  5. Colby RC. The general practitioner’s perspective of the etiology, prevention, and treatment of dry socket. Gen Dent 1997;461-67.
  6. Rood JP, Danford M. Metronidazole in the treatment of dry socket. Int J Oral Surg 1981; 10:345-47. https://doi.org/10.1016/S0300-9785(81)80032-4
  7. Rud J. Removal of impacted lower third molars with acute pericoronitis and necrotizing gingivitis. Br J Oral Surg 1970;7: 153-59. https://doi.org/10.1016/S0007-117X(69)80015-6
  8. Blum IR. Contemporary views on dry socket (alveolar osteitis): a clinical appraisal of standardization, aetiopathogenesis and management: a critical review. Int J Oral Maxillofac Surg 2002; 31: 309-17. https://doi.org/10.1054/ijom.2002.0263
  9. Turner PS. A clinical study of “dry socket.” Int J Oral Surg 1982; 11: 226-31. https://doi.org/10.1016/S0300-9785(82)80071-9
  10. Butler DP, Sweet JB. Effect of lavage on the incidence of localized osteitis in mandibular third molar extraction sites. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1977; 44:14-20. https://doi.org/10.1016/0030-4220(77)90235-3
  11. Trieger N, Schlagel GD. Preventing dry socket: a simple procedure that works. J Am Dent Assoc 1991; 122:67-8. https://doi.org/10.14219/jada.archive.1991.0067
  12. Khawaja NA. Incidence of dry socket in Lower Jaw. Pak Oral Dent J 2006; 26: 227-30
  13. Al-Khateeb TI, EL-Marsafi AI, Butler NP. The relationship between the indications for the surgical removal of impacted third molars and the incidence of alveolar osteitis. Oral Maxillofac Surg 1991; 49: 141- 45. https://doi.org/10.1016/0278-2391(91)90100-Z
  14. Birn H. Etiology and pathogenesis in fibrinolytic alveolitis (dry socket). Int J Oral Surg 1973; 2: 211-63. https://doi.org/10.1016/S0300-9785(73)80045-6
  15. Birn H. Bacteria and fibrinolytic activity in dry socket. Acta Odontol Scand 1970; 28: 773-83. https://doi.org/10.3109/00016357009028246
  16. Amler MH. Pathogenesis of disturbed extraction wounds. J Oral Surg 1973; 31: 666
  17. Karnure M. Review on conventional and novel techniques for treatment of alveolar osteitis. Asian J Pharm Clin Res 2013;6 Suppl 3:13-7
  18. Houston JP, McCollum J, Pietz D, Schneck D. Alveolar osteitis: a review of its etiology, prevention, and treatment modalities. Gen Dent 2002; 50: 457-63.
  19. Akpata O, Omoregie OF, Owotade F. Alveolitis Osteitis: Patients compliance to post-extraction instructions following extraction of molar teeth. Niger Med J 2013; 54:335-38 https://doi.org/10.4103/0300-1652.122360
  20. Doumani M, Habib A, Doumani A et al. The intership dentist’s knowledge about dry socket. Int J Recent Scientific Res 2017; 8: 19941-3.
  21. Santhosh Kumar MP. Knowledge about post extraction complications among undergraduate dental students. J Pharm Sci Res 2016; 8: 470-76.
  22. Catellani JE, Harvey S, Erickson SH, Cherkin D. Effect of oral contraceptive cycle on dry socket (localized alveolar osteitis). J Am Dent Assoc. 1980; 101: 777-80 https://doi.org/10.14219/jada.archive.1980.0420
  23. Ogunlewe MO, Adeyemo WL, Ladeinde AL, Taiwo OA. Incidence and pattern of presentation of dry socket following non-surgical tooth extraction. Nig Q J Hosp Med 2007: 17: 126-30 https://doi.org/10.4314/nqjhm.v17i4.12691
  24. Maria Teberner-vallverdu, Mariam Nazir, Maria Angles SanchezGarces, Cosme Gat-Escode. Efficacy of different methods used for dry socket management: A systematic review. Med Oral Patol Oral Cir Bucal. 2015; 20: https://doi.org/10.4317/medoral.20589
  25. Tarakji B, Saleh LA, Umair A, Azzeghaiby SN, Hanouneh S. Systemic review of dry socket: etiology, treatment, and prevention. J Clin Daign Res 2015; 8: ZE10-13 https://doi.org/10.7860/JCDR/2015/12422.5840
  26. Betts NJ, Makowski G, Shen YH, Hersh EV. Evaluation of topical viscous 2% lidocaine jelly as an adjunct during the management of alveolar osteitis. J Oral Maxillofac Surg 1995; 53: 1140-44. https://doi.org/10.1016/0278-2391(95)90619-3
  27. Hermesch CB, Milton TJ, Biesbrock AR. Perioperative use of 0.12% chlorexidine gluconate for the prevention of alveolar osteitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998; 85: 381- 87. https://doi.org/10.1016/S1079-2104(98)90061-0
  28. Tjernberg A. Influence of oral hygiene measures on the development of alveolitis sicca dolorosa after surgical removal of mandibular third molars. Int J Oral Surg 1979; 8: 430-44. https://doi.org/10.1016/S0300-9785(79)80081-2
  29. Rood JP, Murgatroyd J. Metronidazole in the prevention of “Dry socket.” Br J Oral Maxillofac Surg 1979; 17: 62-70. https://doi.org/10.1016/0007-117X(79)90009-X
  30. Cardoso CL, Rodrigues MTV, Junior OF, Garlet GP, Carvalbo PS. Clinical Concepts of Dry Socket. J Oral Maxillofac Surg 2010; 68:1922-1932 https://doi.org/10.1016/j.joms.2009.09.085
  31. Bystedt H, Nord CE, Nordenram A. Effect of azidocillin, erythromycin, clindamycin and doxycyline on postoperative complications after surgical removal of impacted mandibular third molars. Int J Oral Surg 1980; 9: 157-65. https://doi.org/10.1016/S0300-9785(80)80014-7
  32. Laird WR, Stenhouse D, MacFarlane TW. Control of postoperative infection. A comparative evaluation of clindamycin and phenoxymethylpenicillin. Br Dent J 1972; 133: 106-09. https://doi.org/10.1038/sj.bdj.4802883
  33. Larsen PE. The effect of a chlorhexidine rinse on the incidence of alveolar osteitis following the surgical removal of impacted third molars. J Oral Maxillofac Surg 1991; 49: 932-37. https://doi.org/10.1016/0278-2391(91)90055-Q
  34. Kruger Gustav O. Textbook of Oral & Maxillofacial Surgery. 6th Ed 1984. Saint louis; ISBN-13: 980801627934, Mosby
  35. Akinbami BO, Godspower T. Dry socket, clinical features, and predisposing factors. Int J Dent 2014: 2014: 796102 https://doi.org/10.1155/2014/796102

  1. Faculty, Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, KSU, Riyadh. Former Assistant Professor, HoD, Oral Path, Oral & Maxillofacial Surgery Department, Dental Section, NMC, Multan.
  2. Lecturer, Dental Health Department, College of Applied Medical Sciences, College of Dentistry, King Saud University, Riyadh.
  3. Intern; College of Dentistry, King Saud University, Riyadh.
  4. Intern; College of Dentistry, King Saud University, Riyadh.
    Corresponding author: “Dr. Naveed A. Khawaja” < nakhawaja@yahoo.com >

The Survey of the Knowledge of Dry Socket and Management Among Dental Practitioners; Still Controversy?

Naveed Khawaja           BDS, MCPS, DOMS, MSc-OPath (UK), FADI

Kauser Parveen            BDS, MCPS

Abdullah Almotreb       BDS

Rashed Tashkandi        BDS

OBJECTIVE: Dry Socket (DS) is one of the complications following tooth extraction, reported usually 2-4 days postoperatively with moderate to severe pain. The concept of Dry Socket is not clear and there is disagreement among dental practitioners about diagnosis and management. The objective of this survey was to evaluate the knowledge of dry socket and its treatment among General Practitioners.
METHODOLOGY: One hundred and twenty-nine structured questionnaires were distributed among Dental Practitioners (DP) of Riyadh city with 78% response rate. This study was composed of two part; first about knowledge and second regarding treatment options. Data was collected, tabulated and analyzed using updated SPSS version 22.
RESULTS: According to the results, 75.2% (n=76) practitioners agreed that dry socket is dislodgment of clot in socket, and 20.8% (n=21) agreed that dry socket could be due to contamination of socket. Moreover, 32.7% (n=33) dental practitioners claimed that dry socket patients experienced discomfort symptom but most of the dentists 75.2%n (n=76) reported acute and stabbing pain in dry socket.
CONCLUSION: The overall knowledge of diagnosis and treatment of general practitioners was adequate.
KEY WORDS: Dry Socket; Knowledge; Dental Practitioner; Treatment
HOW TO CITE: Khawaja N, Parveen K, Almotreb A, Tashkandi R. The survey of the knowledge of dry socket and management among dental practitioners; still controversy?. J Pak Dent Assoc 2019;28(4):192-196.
DOI: https://doi.org/10.25301/JPDA.284.192
Received: 21 December 2018, Accepted: 04 September 2019

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Assessment of Knowledge and Practices about Denture Hygiene among Complete Denture Wearers in Lahore City

Muhammad Asif Mushtaq                     BDS

Junaid Altaf                                            BDS

Muhammad Ali Sheikh                          BDS

Muhammad Waseem Ullah Khan         BDS, FCPS

Asif Ali Shah                                          BDS, MSc, MDS

OBJECTIVE: The aim of this study was to determine the level of awareness about knowledge and practices of complete denture hygiene in a tertiary care dental hospital of Lahore.
METHODOLGY: A descriptive, cross-sectional study was conducted in the Department of Prosthodontics, Punjab Dental Hospital/de’Montmorency College of Dentistry, Lahore. A total of 150 patients were included in the study. All patients were selected randomly who were seeking treatment from this tertiary care dental hospital. The questionnaire included data about gender, age, duration of prosthesis use, cleaning methods and materials etc. The collected data was analyzed using SPSS version 20.0. Chi-square test of significance was applied for statistical analysis with a significance level of 5% (p=0.05).
RESULTS: The results showed that 49 (32.7%) subjects were wearing the same prosthesis for more than 5 years. Data analysis showed that 44 out of 150 subjects (29.3%) normally slept with their prosthesis in mouth. 86 patients (57.3%) told that they were given only verbal instructions about methods of cleaning while 64 (42.7%) were not even told or shown any method of cleaning of denture by dentist. It was observed that 63 individuals (42%) believe that denture can last from 5-10 years.
CONCLUSIONS: Within the limitations of this study, it was concluded that complete denture wearers had limited awareness of denture hygiene and oral care despite using dentures for long time.
KEY WORDS: Complete denture, Oral hygiene, Denture cleansing, Dental care.
HOW TO CITE: Mushtaq MA, Altaf J, Sheikh MA, Khan MWU, Shah AA. Assessment of knowledge and practices about denture hygiene among complete denture wearers in lahore city. J Pak Dent Assoc 2019;28(4):187-191.
DOI: https://doi.org/10.25301/JPDA.284.187
Received: 20 February 2019, Accepted: 09 August 2019

INTRODUCTION

According to latest demographic data, life expectancy has increased in both developing and developed countries. The proportion of older people has increased in correspondence to the total population. Approximately 600 million people are of 60 or above worldwide and this number is expected to be doubled by 2025. The process of ageing is relentless leading to inconsistent homeostasis, raised susceptibility to chronic diseases alongwith decreased reconciliation to external environmental stimuli which affects bodily organs and systems. All these aspects are consociated with more predisposition to systemic diseases and death.1,2 Several current studies indicate that association is existing between oral diseases and systemic chronic diseases.3
Agonies of old age can be reduced by treating oral diseases alongwith systemic chronic diseases. Despite many advancements in preventive and conservative dentistry, various oral diseases like dental caries, tooth wear lesions, periodontal diseases, trauma and tumors of the jaw lead to loss of many teeth and ultimately edentulism.2
The most common treatment worldwide for edentulism is removable complete denture.2,4 Maintenance of optimum oral health in denture wearers becomes more difficult which can lead to malodor, poor esthetics, accumulation of plaque/calculus on denture, soft tissue pathologies and even complete failure of the prosthesis. In complete denture wearers, poor oral health can be attributed to inadequate oral hygiene, poor manual dexterity, surface roughness of the prosthesis, lack of proper instructions and guidance by the dentist and failure to follow the instructions given by dentist.4,5
The main objective of complete denture prosthetic treatment is to improve patient’s health by restoring function. The success of this treatment depends on patients’ motivation towards correct method of use, maintenance of good oral hygiene and proper guidance by the dentist. Current literature has revealed that patients are not given proper instructions for denture cleansing, general oral health care and need for follow up dental visits.2,6 According to American College of Prosthodontists recommendations for care and maintenance of denture, daily careful removal of biofilm present in the oral cavity and on denture surface is of utmost importance for good oral and general health.7
Home care instructions are given to the patient to remove this biofilm. Generally, two major methods are recommended for biofilm removal from denture surface. These methods include mechanical cleaning, chemical cleaning or combination of both. Although literature has shown the most effective and common method is mechanical cleaning but chemical cleansers are also used with mechanical methods.8,9,10 According to Azad et al, 65% complete denture wearers clean their denture once only and major method of cleaning was water.11 Barbosa et al have mentioned that only 16.8% complete denture wearers were using chemical denture disinfectants.6 Shankar et al have reported that 10.2% complete denture wearers not given any denture hygiene instructions.2
As shown by these studies, there is immense need of improving denture hygiene knowledge and practices in every part of the world. The objective of this questionnaire based study was to assess the knowledge of complete denture wearers about denture hygiene visiting a tertiary care hospital in Lahore city. This knowledge and practice assessment was used to determine the level of awareness about denture care and maintenance .According to previous studies, there was need to increase the standard of denture hygiene habits in complete denture wearers. So, there is continuous need of reassessment of knowledge about denture hygiene habits. This evaluation will help clinicians to emphasize more on denture hygiene by better patient education.

METHODOLOGY

This cross sectional descriptive study was conducted in the Department of Prosthodontics, Punjab Dental Hospital/de’Montmorency College of Dentistry, Lahore from May, 2018 to December, 2018. Permission from the hospital ethical committee was taken. Informed consent Performa was filled for every patient. It was made sure that every patient understands the purpose of study and its clinical implications. They were assured about the confidentiality of their collected data. A total of 150 patients were interviewed and included in study. All patients were selected randomly who were seeking treatment from this tertiary care dental hospital. The validated questionnaire was prepared from previous studies.6,12
The collected data was analyzed using SPSS version 20.0. Percentages and frequencies were calculated for categorical variables like methods of denture cleansing, gender, age of denture. Mean and standard deviation was calculated for numerical variables like age. Chi-square test of significance was applied for statistical analysis keeping p <0.05 as significant.

RESULTS

A total of 150 patients were selected, 102 of whom (68%) were male and 48 (32%) were female. The age range was 21-95 years with a mean age of 63.39 years with 59.3% between 50-70 years of age (Fig.1). Patients were categorized according to the duration of usage of prosthesis in three

Fig 1: Age Distribution of Participants

groups with at least 6 months of usage. 6 months to one year group was of n=50 (33.3%), 1-5 year group was n=51 (34%), more than five years use was n=49 (32.7%). Data analysis showed that 44 out of 150 subjects (29.3%) normally slept with their prosthesis in mouth (Fig.2) out of these 44,35 were male and 9 were female and a chi square was performed with weak relationship between gender and sleeping with prosthesis (x2=3.81, p=0.051) (Table.1). Major method of When questioned about frequency of cleaning their complete denture daily, 66 subjects (44%) reported cleaning their prosthesis once a day while only 42 individuals (28%) reported cleaning their prosthesis three or more times a day and strong relationship was found between gender and frequency of cleaning the prosthesis (x2=14.58, p=0.002)

Sleeping with Complete denture in mouth

Fig 2: Percentage of participants sleeping with prosthesis in month

How many times clean prothesis in a day

Fig 3: Frequency of cleaning of prosthesis

Table 1: Denture hygiene knowledge and practices across gender

(Fig.3). Methods of cleaning were water (100%), toothbrush (71.3%), soap (36%), toothpaste alongwith water (23.3%). Only 1 patient (0.7%) reported of using disinfecting denture cleanser solution. Only 15 (10%) of the study subjects said they used a denture adhesive to aid in prosthesis retention. 145 subjects (96.7%) believe that they can clean their prosthesis properly. It was observed that 63 individuals (42%) individuals believe that denture can last from 5-10 years.
When asked about instructions given by the dentist or dental staff, 86 patients (57.3%) told that they were given only verbal instructions about methods of cleaning while 64 (42.7%) were not given any verbal instructions or practical demonstrations about any method of cleaning of denture.

DISCUSSION

The questionnaire for this study contained queries about several factors that can be attributed to the etiology of denture stomatitis i.e. duration of denture use, denture hygiene practices and lack of instructions by the dental professional for oral and denture hygiene maintenance. The study sample of 150 subjects was almost equally distributed among three groups regarding duration of denture use which is in agreement with the study done by Shankar et al2 and Peracini et al.8 However, studies done by Barbosa et al6 and Coelho et al 13 reported 75 % of the participants with denture usage of more than five years.
The present study reports that 29.3% subjects were sleeping with their denture in mouth overnight. In contrast, Shankar et al2 reported 13.2% subjects sleeping with prosthesis overnight. Some other studies had shown more complete denture wearers sleeping with prosthesis overnight with percentages ranging between 64 %6, 58.9%12 and
55.2% 14 respectively. Frequency of denture stomatitis was more in subjects who were wearing their dentures while
sleeping at night.15
When prosthesis was not in use e.g. at night, the major method of storage was plain water (95.3%), which is significantly different from the study by Shankar et al 2 70%.
While other methods employed for storage of prosthesis were placing dentures in pocket, plastic bag or under pillow.
This finding is in line with post-operative instructions given by the dentist.
In this study population, it was a surprising finding that 100% subjects were cleaning their prosthesis at least once a day. This result is similar to a study by Barbosa et al6 (98%) and Marchini et al16 (98.7%). There is strong correlation between unsatisfactory cleaning of prosthesis and candida infection.6
When asked about method of cleaning, commonly used method was plain tap water by 100% subjects, while 71.3% subjects also used toothbrush along with water which is the results of Barbosa et al6 and Peracini et al.17 Other methods were toothbrush along with toothpaste and soap. While answering the query about the use of disinfecting
materials, only one individual of the study sample was found to be using commercially available disinfecting denture cleansing solution in contrast to other studies which reported 16.8% 6 and 11.4% 2 of the sample size. Chemical cleansing agents are mainly cleaning tablets and sodium hypochlorite solution. According to Peltola et al18, the use
of denture immersion disinfecting solution was infrequent (27.1%) and most common immersion solution used was
sodium hypochlorite (54.7%).
Denture adhesive use was the major assistance required by the patients for adaptation to new dentures.15 subjects (10%) of the study sample were using denture adhesives. In another study, this percentage was only 1.3%6 and a study without a single user of adhesive.19 When asked about satisfaction with the method of cleaning, astonishingly 96.7% individuals were satisfied.
But, Hoadreddick et al12 had revealed in a study that 34.6% of individuals were not satisfied with their methods of cleaning.
When enquired about the perception of age of complete denture, 81.3% of the subjects believed that complete denture can last 5-10 years while 14.7 % believe denture can last longer than 10 years. While study by Barbosa et al6
showed 44% denture wearers believe denture can last more than 10 years.
Enquiry about provision of denture hygiene instructions revealed that 57.3% subjects were only told about methods
of denture cleaning by the dentist or any of the dental staff. The study by Hoadreddick et al12 has shown much better
percentage than this i.e.86.3% which were given verbal instructions about cleansing of denture and oral cavity. Old
denture wearers are more susceptible to oral mucosal lesions, such as, denture stomatitis, angular cheilitis, candida
infections and burning mouth syndrome. Denture care instructions should include the complete care about dentures
and oral hard and soft tissues along with practical demonstrations by the dentist or dental staff.2 Daily oral hygiene habits are of prime importance as preventive method for mucosal lesions.20
Dentists should not only fabricate prosthesis but also provide their patients with detailed practical and realistic guidelines for the maintenance of prosthesis and oral hard and soft tissues. Complete denture patients should be instructed about the removal of prosthesis at night as well as the need to visit their dentist periodically for prosthesis and oral cavity evaluation.2,21

CONCLUSIONS

It is concluded that within the limitations of this study, most of the denture wearers had little knowledge of denture cleaning and hygiene practices. This study had revealed that oral hygiene habits and practices may not always be correlated positively with age, gender, method of prosthesis care and number of years of usage of prosthesis. By maintaining excellent denture hygiene, complete denture wearers can get maximum benefit out of their prosthesis for a longer period of time.

CONFLICT OF INTEREST

None declared

REFERENCES

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  1. FCPS Resident, Department of Prosthodontics, de’Montmorency College of Dentistry Punjab Dental Hospital, Lahore.
  2. FCPS Resident, Department of Prosthodontics, de’Montmorency College of Dentistry Punjab Dental Hospital, Lahore.
  3. FCPS Resident, Department of Prosthodontics, de’Montmorency College of Dentistry Punjab Dental Hospital, Lahore.
  4. Assistant Professor, Department of Prosthodontics, de’Montmorency College of Dentistry Punjab Dental Hospital, Lahore.
  5. Professor, Department of Prosthodontics, de’Montmorency College of Dentistry Punjab Dental Hospital, Lahore.
    Corresponding author: “Dr. Muhammad Asif Mushtaq” < dr.asif100@yahoo.com >

Assessment of Knowledge and Practices about Denture Hygiene among Complete Denture Wearers in Lahore City

Muhammad Asif Mushtaq                     BDS

Junaid Altaf                                            BDS

Muhammad Ali Sheikh                          BDS

Muhammad Waseem Ullah Khan         BDS, FCPS

Asif Ali Shah                                          BDS, MSc, MDS

OBJECTIVE: The aim of this study was to determine the level of awareness about knowledge and practices of complete denture hygiene in a tertiary care dental hospital of Lahore.
METHODOLGY: A descriptive, cross-sectional study was conducted in the Department of Prosthodontics, Punjab Dental Hospital/de’Montmorency College of Dentistry, Lahore. A total of 150 patients were included in the study. All patients were selected randomly who were seeking treatment from this tertiary care dental hospital. The questionnaire included data about gender, age, duration of prosthesis use, cleaning methods and materials etc. The collected data was analyzed using SPSS version 20.0. Chi-square test of significance was applied for statistical analysis with a significance level of 5% (p=0.05).
RESULTS: The results showed that 49 (32.7%) subjects were wearing the same prosthesis for more than 5 years. Data analysis showed that 44 out of 150 subjects (29.3%) normally slept with their prosthesis in mouth. 86 patients (57.3%) told that they were given only verbal instructions about methods of cleaning while 64 (42.7%) were not even told or shown any method of cleaning of denture by dentist. It was observed that 63 individuals (42%) believe that denture can last from 5-10 years.
CONCLUSIONS: Within the limitations of this study, it was concluded that complete denture wearers had limited awareness of denture hygiene and oral care despite using dentures for long time.
KEY WORDS: Complete denture, Oral hygiene, Denture cleansing, Dental care.
HOW TO CITE: Mushtaq MA, Altaf J, Sheikh MA, Khan MWU, Shah AA. Assessment of knowledge and practices about denture hygiene among complete denture wearers in lahore city. J Pak Dent Assoc 2019;28(4):187-191.
DOI: https://doi.org/10.25301/JPDA.284.187
Received: 20 February 2019, Accepted: 09 August 2019

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