|Year : 2021 | Volume
| Issue : 4 | Page : 222-226
Oral manifestations of white blood cell dyscrasias with emphasis on their management
Amritha James, Sahanaz Praveen Ahmed, Preethi Arunachalam, Ramya Mahalingam, Vaddadi Krishna Mohan
Department of Oral Pathology and Microbiology, SRM Dental College, Ramapuram, Chennai, Tamil Nadu, India
|Date of Submission||31-Mar-2021|
|Date of Decision||06-Oct-2021|
|Date of Acceptance||08-Oct-2021|
|Date of Web Publication||20-Dec-2021|
Dr. Amritha James
Department of Oral Pathology, SRM Dental College, Bharathi Salai, Ramapuram, Chennai - 600 089, Tamil Nadu
Source of Support: None, Conflict of Interest: None
White blood cell (WBC) dyscrasias refer to a group of disorders that affect the WBCs or their precursors. Oral manifestations are often the first identifiable signs of such disorders. A clear knowledge about these manifestations is necessary for both the dentist and the general physicians to initiate treatment at the earliest which could prove as a matter of life or death for the patient in certain malignancies. There is no comprehensive review on the oral manifestations of WBC dyscrasias till date. Hence, the aim of this review is to present the oral manifestations of the most commonly encountered WBC dyscrasias and their treatment modalities with an emphasis on dental management.
Keywords: Blood dyscrasias, management, oral manifestation, white blood cells
|How to cite this article:|
James A, Ahmed SP, Arunachalam P, Mahalingam R, Mohan VK. Oral manifestations of white blood cell dyscrasias with emphasis on their management. SRM J Res Dent Sci 2021;12:222-6
|How to cite this URL:|
James A, Ahmed SP, Arunachalam P, Mahalingam R, Mohan VK. Oral manifestations of white blood cell dyscrasias with emphasis on their management. SRM J Res Dent Sci [serial online] 2021 [cited 2022 Nov 26];12:222-6. Available from: https://www.srmjrds.in/text.asp?2021/12/4/222/332892
| Introduction|| |
White blood cells (WBCs), also called leukocytes, are the main defense cells that protect our body from invading pathogens. WBCs are broadly classified into granulocytes and agranulocytes. Neutrophils, eosinophils, and basophils are granulocytes while lymphocytes and monocytes are classified under agranulocytes as they lack granules in their cytoplasm.
WBC dyscrasias refer to a group of disorders that affect the WBCs or their precursors. The most common WBC disorders with oral manifestations have been discussed [Figure 1]. Oral manifestations are often the first identifiable signs of such disorders, and identifying them at early stages could mean the difference of life and death for such patients. Dentists are often the first health-care providers who can recognize such lesions and hence play a vital role in diagnosis of such disorders. There is no comprehensive review on the oral manifestations of WBC dyscrasias till date. Hence, the aim of this review is to present the oral manifestations of the most commonly encountered WBC dyscrasias along with their management from a dentist's perspective.
|Figure 1: Origin of common white blood cell disorders with manifestations in the oral cavity|
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| Cyclic Neutropenia|| |
Neutropenia is a disorder characterized by decrease in circulating neutrophils below 1.5 × 109/L. Neutropenia can be “transient” as seen in bacterial and viral infections and use of certain drugs, or they can be “chronic” (lasting more than 3 months) as seen in aplastic anemia and cyclic neutropenia.
Cyclic neutropenia is a disorder characterized by periodic decrease of circulating neutrophils in blood that occurs every 21 days and usually lasts for 3–6 days. It is a genetic disorder caused by mutations in the ELA2 gene and is passed down as an autosomal dominant disorder. Patients present with fatigue, fever, lymphadenopathy, and frequent infections during neutropenic phases. In the current era of pandemic, reports of acute death due to cyclic neutropenia in patients diagnosed with coronavirus disease have also been reported. Hence, diagnosing oral manifestations of cyclic neutropenia at the earliest can help in early diagnosis and appropriate treatment strategies.
| Oral Manifestations|| |
Oral manifestations of cyclic neutropenia include gingivitis, periodontitis, and recurrent painful oral ulcerations involving the tongue, buccal mucosa, and lips. Recurrent oral infections are also common., In children, repeated infection often leads to considerable loss of supporting bone around the tooth and ultimately early tooth loss.
| Dental Management|| |
Treatment involves administration of filgrastim or pegfilgrastim which is recombinant granulocyte colony-stimulating factor (G-CSF) that promotes the proliferation and differentiation of granulocytes and can increase the levels of circulating neutrophils within a short duration and thus alleviate the symptoms of neutropenia.
Scaling and root planing should be done to reduce periodontal destruction and maintain oral health. If extraction is indicated, G-CSF and antibiotic prophylaxis must be initiated prior to the start of the therapy.
| Leukemia|| |
Leukemias are neoplastic disorders that involve the proliferation of underdeveloped white cells in the bone marrow. Leukemias are most commonly encountered in the elderly and children under 10 years and have a male predilection. Based on the progenitor cell involved, they can be either of the myeloid origin or lymphoid origin, and based on the duration of the disease, they can be either acute or chronic.
Acute myeloid leukemia
Acute myeloid leukemia (AML) is an aggressive disease that is most commonly seen in elderly patients. This disease is more common in males than females. It is characterized by accrual of immature myeloid cells in the bone marrow and peripheral blood. The exact cause of the disease is unknown, but several factors have been implicated including hereditary inheritance, environmental factors, drugs, and radiation. Patients with AML usually present with leukocytosis, thrombocytopenia, and anemia that results from bone marrow failure due to its infiltration by the malignant blast cells.
Oral manifestations are the first identifiable signs of AML and are caused by pancytopenia. Patients present with gingival bleeding and petechial hemorrhages of the gingiva, palate, tongue, or lips due to thrombocytopenia. Mucosal pallor may be present due to anemia. Oral ulcerations are also frequently seen due to neutropenia., Gingival hyperplasia is seen due to leukemic cell infiltration which may be mild and involve only the interdental papilla or may involve the gingiva as a whole covering the entire tooth surface impairing function and esthetics. Immunosuppression in such patients can also cause recurrent bacterial, viral, and fungal infections in the oral cavity. Intraoral myelosarcomas have also been associated with AML., Sweet's syndrome has also been linked with AML.
Chronic myeloid leukemia
Chronic myeloid leukemia (CML) is characterized by infiltration of bone marrow and peripheral blood by relatively well-differentiated, transformed hematopoietic progenitor cells and is most commonly seen in adults between 45 and 55 years. CML is caused due to reciprocal translocation of BCR region of chromosome 22 and ABL region of chromosome 9. This translocation results in tyrosine kinase activation promoting cell division and evasion of apoptosis in mature myeloid cells. Fatigue, weight loss, purpura, splenomegaly, and anemia are the most common presenting signs.
Oral manifestations in CML are rarely seen. Petechiae and mucosal bleeding can occur as a result of thrombocytopenia. Acute periodontitis and candidiasis can occur due to altered bacterial flora. Gingival enlargement occurs due to infiltration of the gingiva by the immature cells. Intraoral granulocytic sarcomas have been associated with CML, with only a few reported cases in the literature. It presents as generalized gingival overgrowth, gingival bleeding, and periodontal disease.
Acute lymphoblastic leukemia
Acute lymphoblastic leukemia (ALL) is characterized by proliferation of lymphoblasts which grow uncontrollably and eventually displace the cells of the normal bone marrow. The disease is commonly seen in childhood. Based on the type of lymphocyte involved, it is further classified into B-cell ALL, T-cell ALL, and natural killer cell ALL. Patients with ALL present initially with nonspecific signs such as fatigue, pallor, fever, and spontaneous bleeding. Patients may also present with hepatomegaly and splenomegaly and may show extranodal involvement of central nervous system and testicles.
Oral manifestations of ALL include gingival bleeding, mucosal pallor, pain, gingival overgrowth, extensive oral ulcerations, and oral mucosal infections such as candidiasis, herpes simplex/varicella-zoster infections, and infections with CMV. Unilateral maxillary swelling was also reported in a case as the first sign of relapse of ALL. Other signs such as numbness of the chin, pericoronitis, and trismus have also been reported as primary manifestations of ALL.
Chronic lymphocytic leukemia
Chronic lymphocytic leukemia (CLL) is usually an accidental finding during complete blood counts. It is the most common leukemia affecting the elderly, especially the Western countries. Incidence of CLL is comparatively rare in Asian countries. Patients on examination usually present with signs of fatigue, unintentional weight loss, intermittent fever, pallor, frequent infections, bleeding tendencies, and lymphadenopathy.
Oral manifestations in CLL are rare. Generalized lymphadenopathy of the head-and-neck region is the most common manifestation of CLL. Patients may also present with gingival bleeding and petechial hemorrhages which may be a consequence of thrombocytopenia. Oral ulcerations and opportunistic infections like candidiasis are also seen due to decrease in granulocytes. Palatal, mandibular, and gingival enlargement due to leukemic cell infiltration has also been reported.
| Dental Management of Leukemias|| |
Gingival hypertrophy and gingival bleeding can be managed by meticulous maintenance of oral hygiene and the use of topical antiseptics like chlorhexidine mouth rinse. Oral ulcerations can be treated with topical corticosteroids (fluocinonide 0.05% gel) and antibiotic therapy. Antibiotics and antifungals can be administered to treat bacterial and fungal infections. Oral health of such patients must be maintained during and after antineoplastic therapy as well. Patients must be educated on the possibility of developing oral mucositis, xerostomia, dysgeusia, and oral infections.
| Hodgkin'S Lymphoma|| |
Hodgkin's disease or Hodgkin's lymphoma (HL) is a neoplastic disorder of lymphoid origin characterized by the presence of Reed–Sternberg cells. The disease has a bimodal age distribution and is seen in young adults (15–20 years) and the elderly (>55 years) with a male predominance. It is characterized by painless enlargement of lymph nodes, most commonly the mediastinal nodes, hilar and cervical group of lymph nodes. The etiology of the disease is unknown, but it shows a strong association with Epstein–Barr virus infection. Patients present with systemic signs of fever, night sweats, unexplained weight loss, and pruritus.,
| Oral Manifestations|| |
Oral manifestations in HL are rare. Primary lesions usually involve the Waldeyer's ring. Within the oral cavity, extranodal HL most commonly involves the tonsil, but other sites such as the base of the tongue, buccal mucosa, and palate have also been reported. It presents as a painless, slow-growing swelling which may or may not be ulcerated.
| Dental Management|| |
HL is treated with adriamycin, bleomycin, vinblastine, and dacarbazine therapy (treatment with the chemotherapy drugs) or radiotherapy. Hence, any focus of infections present in the oral cavity has to be identified and treated at the earliest to avoid complications during subsequent chemotherapy. Meticulous maintenance of oral hygiene and the use of topical antiseptics like chlorhexidine mouth rinse can help alleviate oral pain and ulcerations during chemotherapy.
| Burkitt'S Lymphoma|| |
Burkitt's lymphoma, also called African jaw lymphoma, is a B-cell neoplasm that presents itself in two forms: endemic form (African) and sporadic form. The endemic form often involves the maxilla or mandible and is seen in association with the African population while the sporadic form affects the abdominal organs such as the distal ileum and cecum and is seen throughout the world. The disease affects children between 3 and 8 years of age with a male predilection. The exact cause of the disease is unknown, but many etiologies have been suggested including infection with Epstein-Barr virus and translocation of the c-myc oncogene. Ninety percent of Burkitt's lymphoma shows translocation of c-myc oncogene from chromosome 8 to chromosome 14 or 22.,
| Oral Manifestations|| |
Burkitt's lymphoma most commonly affects the maxilla when compared to the mandible. Patients present with swelling of the affected jaw, mobility of tooth in the associated region, and nontender swelling of the cervical or submandibular lymph nodes.
| Dental Management|| |
Treatment of Burkitt's lymphoma is carried out by multi-agent chemotherapy and rituximab (a monoclonal anti-CD20 antibody). Maintenance of oral hygiene by thorough oral prophylaxis is necessary to reduce periodontal destruction.
| Multiple Myeloma|| |
Multiple myeloma is a neoplastic disorder of hematological origin characterized by excess proliferation of atypical plasma cells which eventually replace the marrow cells and produce excess immunoglobulins which have abnormal physiochemical properties. The disease is commonly seen in elderly patients with a male predominance. The disease manifests as bone lytic lesions, anemia, renal insufficiency, and hypercalcemia. Patients present with signs of bone pain, anemia, fatigue, and weightless and presence of M protein in the serum and urine.
| Oral Manifestations and Their Management|| |
Oral manifestations of multiple myeloma include swelling, bone pain, mobility of teeth, paresthesia, ulceration, hemorrhage, and fracture involving the maxilla and mandible caused by destruction of bone by the proliferating tumor cells. The mandible is more commonly affected when compared to the maxilla, with the ramus, angle, and molar region of the mandible being the most frequently affected sites.,, Swelling involving the jaws is seen in advanced cases of the disease but sometimes may also represent the first sign of the disease., Radiographically numerous punched out radiolucent lesions are seen involving the jaws ranging from a few millimeters to centimeter or more in diameter. Extramedullary plasmacytomas involving the oral cavity have also been reported as the initial manifestation of multiple myeloma and may resemble gingival enlargements.
Patients with multiple myeloma are treated with chemotherapy and bisphosphonate therapy. Oral foci of infections have to be removed prior to initiating antineoplastic therapy. Extramedullary plasmacytomas are treated with complete surgical excision.
| Langerhans Cell Histiocytosis|| |
Langerhans cell histiocytosis is a disorder characterized by atypical clonal proliferation of Langerhans cells. The disease is perceived most often in children between 1 and 4 years with a male predilection.
Langerhans histiocytosis most commonly involves the gingiva and the hard palate. Oral manifestations of the disease include ulceration, bleeding, and swelling involving the gingiva and palate. Lesions may also involve the jaws and manifest as pain and swelling of the mandible, with mobility and loss of tooth.
| Dental Management|| |
Treatment is carried out by surgical excision, chemotherapy, radiotherapy, or combination of these treatments. Localized mandibular and maxillary lesions can be treated by surgical curettage, and subsequent bone grafts can be made to reduce the risk of pathological fracture.
| Conclusion|| |
Oral manifestations are often the first signs of WBC disorders. An in-depth knowledge of the various oral manifestations of WBC disorders is necessary in order to diagnose them at the earliest. As the popular saying goes, “The eyes cannot see what the mind does not know” is quite apt in regard to this. The current article briefly summarizes the oral manifestation of common WBC disorders for the reference of general dentists. Dentists are the first health-care providers to encounter such lesions, and most of these soft-tissue lesions are often overlooked. Hence, the article purely aims to enlighten the dentist of the oral manifestations and current treatment modalities that can be undertaken by the dentist to curb such oral manifestations.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Matarasso S, Daniele V, Iorio Siciliano V, Mignogna MD, Andreuccetti G, Cafiero C. The effect of recombinant granulocyte colony-stimulating factor on oral and periodontal manifestations in a patient with cyclic neutropenia: A case report. Int J Dent 2009;2009:654239.
Leister J, McCarthy L. Pediatric coronavirus (COVID-19) death in a child with cyclic neutropenia. Pediatr Blood Cancer 2021;68:e29171.
Chen Y, Fang L, Yang X. Cyclic neutropenia presenting as recurrent oral ulcers and periodontitis. J Clin Pediatr Dent 2013;37:307-8.
Rosa BP, Ito FA, Trigo FC, Mizuno LT, Takahama A Jr. Oral Manifestation as the Main Sign of an advanced stage acute promyelocytic leukemia. Acta Stomatol Croat 2018;52:358-62.
Grigoropoulos NF, Petter R, Van 't Veer MB, Scott MA, Follows GA. Leukaemia update. Part 1: Diagnosis and management. BMJ 2013;346:f1660.
Burke VP, Startzell JM. The leukemias. Oral Maxillofac Surg Clin North Am 2008;20:597-608.
Guan G, Firth N. Oral manifestations as an early clinical sign of acute myeloid leukaemia: A case report. Aust Dent J 2015;60:123-7.
Francisconi CF, Caldas RJ, Oliveira Martins LJ, Fischer Rubira CM, da Silva Santos PS. Leukemic oral manifestations and their management. Asian Pac J Cancer Prev 2016;17:911-5.
Pyati SA, Naveen Kumar R, Kumar V, Praveen Kumar NH, Parveen Reddy KM. Salivary flow rate, pH, buffering capacity, total protein, oxidative stress and antioxidant capacity in children with and without dental caries. J Clin Pediatr Dent 2018;42:445-9.
Osterne RL, Matos-Brito RG, Alves AP, Nogueira TN, Rocha-Filho FD, Meneses FA, et al.
Oral granulocytic sarcoma: A case report. Med Oral Patol Oral Cir Bucal 2009;14:E232-5.
Wang D, He K, Sroussi H, Treister N, Luskin M, Villa A, et al.
Oral myeloid sarcoma as an uncommon manifestation of acute myeloid leukemia: A case series and review of the literature. J Am Dent Assoc 2021;152:393-400.e8.
Kumar V, Abbas AK, Aster JC. Robbins and Cotran Pathologic Basis OS Disease. Elsevier India; 2015. p. 113-35.
da Silva-Santos PS, Silva BS, Coracin FL, Yamamoto FP, Pinto DD Jr., Magalhães MG. Granulocytic sarcoma of the oral cavity in a chronic myeloid leukemia patient: An unusual presentation. Med Oral Patol Oral Cir Bucal 2010;15:e350-2.
Aronovich S, Connolly TW. Pericoronitis as an initial manifestation of acute lymphoblastic leukemia: A case report. J Oral Maxillofac Surg 2008;66:804-8.
Anirudhan D, Bakhshi S, Xess I, Broor S, Arya LS. Etiology and outcome of oral mucosal lesions in children on chemotherapy for acute lymphoblastic leukemia. Indian Pediatr 2008;45:47-51.
Fallahinejad Ghajari M, Moshref M, Taghipour E. Maxilla unilateral swelling as the first diagnostic symptom of acute lymphoblastic leukemia relapse: A case report. J Dent (Tehran) 2011;8:44-7.
Schaedel R, Goldberg MH. Chronic lymphocytic leukemia of B-cell origin: Oral manifestations and dental treatment planning. J Am Dent Assoc 1997;128:206-10.
Vibhute P, Carneiro E, Genden E, Som PM. Palatal enlargement in chronic lymphocytic leukemia. AJNR Am J Neuroradiol 2006;27:1649-50.
Shanbhag S, Ambinder RF. Hodgkin lymphoma: A review and update on recent progress. CA Cancer J Clin 2018;68:116-32.
Küppers R, Engert A, Hansmann ML. Hodgkin lymphoma. J Clin Invest 2012;122:3439-47.
Darling MR, Cuddy KK, Rizkalla K. Hodgkin lymphoma of the oral mucosa. Head Neck Pathol 2012;6:507-10.
Rajendran A, Sundaram S. Shafer's Textbook of Oral Pathology. Elsevier India; 2012. p. 1001.
Freitas RD, Barros SS, Quinderé LB. Oral burkitt's lymphoma – Case report. Braz J Otorhinolaryngol 2015;74:458-61.
Ardekian L, Rachmiel A, Rosen D, Abu-El-Naaj I, Peled M, Laufer D. Burkitt's lymphoma of the oral cavity in Israel. J Cranio-Maxillofac Surg 1999;27:294-7.
Ferry JA. Burkitt's lymphoma: Clinicopathologic features and differential diagnosis. Oncologist 2006;11:375-83.
Almeida TM, Cavalcanti ÉF, Freitas AD, Magalhães RJ, Maiolino A, Torres SR. Can dentists detect multiple myeloma through oral manifestations? Rev Bras Hematol Hemoter 2018;40:43-9.
Shah A, Ali A, Latoo S, Ahmad I. Multiple myeloma presenting as gingival mass. J Maxillofac Oral Surg 2010;9:209-12.
Barket Ali AA, Azeem M, Bhutto N, Raza Shaikh S. Determinants of job satisfaction among dentists working in teaching hospitals in Karachi, Hyderabad and Islamabad. J Dent Craniofac Res 2018;02:1-3.
Vieira-Leite-Segundo A, Lima Falcão MF, Correia-Lins Filho R, Marques Soares MS, López López J, Chimenos Küstner E. Multiple myeloma with primary manifestation in the mandible: A case report. Med Oral Patol Oral Cir Bucal 2008;13:E232-4.
Ramaiah KK, Joshi V, Thayi SR, Sathyanarayana P, Patil P, Ahmed Z. Multiple myeloma presenting with a maxillary lesion as the first sign. Imaging Sci Dent 2015;45:55-60.
Liardo C, Villari L, Ferlito S, Conticello C, Di Raimondo F, Vetro C, et al
. Oral lesion as unusual first manifestation of multiple myeloma: Case reports and review of the literature. Case Rep Hematol 2014;2014:1-7.
Altay MA, Sindel A, Özalp Ö, Kocabalkan B, Özbudak İH, Erdem R, et al.
Langerhans cell histiocytosis: A diagnostic challenge in the oral cavity. Case Rep Pathol 2017;2017:1691403.
Divya KS. Oral manifestion of Langerhans cell histiocytosis mimicking inflammation. Indian J Dent Res 2014;25:228-30.
] [Full text]
García de Marcos JA, Dean Ferrer A, Alamillos Granados F, Ruiz Masera JJ, Barrios Sánchez G, Romero Ortiz AI, et al.
Langerhans cell histiocytosis in the maxillofacial area in adults. Report of three cases. Med Oral Patol Oral Cir Bucal 2007;12:E145-50.