```markdown THE UNIVERSITY OF WESTERN AUSTRALIA | Oral Health Centre of Western Australia Haematological diseases and immunodeficiency Bobby Joseph Associate Professor 2026 ``` Bobby Joseph Associate Professor 2026 # Learning Outcomes - Gain an understanding of an overview of haematological diseases and immunodeficiency - To recognise the oral manifestations and management of patients with these conditions - To develop an awareness when medically compromised patients should be referred to secondary care Upon completion of this section, students should be able to: - Gain an understanding of an overview of haematological diseases and immunodeficiency. - Recognise the oral manifestations and management of patients with these conditions. - Develop an awareness of when medically compromised patients should be referred to secondary care. # Anaemia - Term used for either a decrease in the volume of RBC or in the concentration of haemoglobin - Result from decreased production of RBCs or increased destruction or loss (trauma, menstruation, GI bleeding) of RBCs - General symptoms are related to reduced oxygen-carrying capacity of blood - Tiredness, shortness of breath, tachycardia and palpitations - Pallor of mucous membrane Anaemia is a term used for either a decrease in the volume of red blood cells (RBC) or in the concentration of haemoglobin. #### Pathophysiology - Results from decreased production of RBCs or increased destruction or loss (trauma, menstruation, GI bleeding) of RBCs. #### General Symptoms Symptoms are related to the reduced oxygen-carrying capacity of the blood: - Tiredness and shortness of breath - Tachycardia and palpitations - Pallor of the mucous membrane # Iron-deficiency anaemia - Most common cause of anaemia - Classified as hypochromic microcytic anaemia ## Causes - Decreased dietary intake of iron - Decreased absorption of iron (e.g. Coeliac disease) - Excessive blood loss (e.g. menstrual or GI bleeding) - Increased demand for red blood cells (e.g. pregnancy) ## Signs and symptoms - Fatigue, dyspnoea - Koilonychia (spoon-shaped) nails, pica (craving for specific foods/dirt), blue sclera ## Oral findings - Pale oral mucosa - Depapillated atrophic tongue - Glossodynia (burning sensation) - Candidiasis/Angular cheilitis - Aphthous-like ulcers <img src="https://i.imgur.com/koilonychia.jpg" alt="Koilonychia (spoon-shaped) nail"> <img src="https://i.imgur.com/atrophic_tongue.jpg" alt="Depapillated atrophic tongue">   Iron-deficiency anaemia is the most common cause of anaemia and is classified as hypochromic microcytic anaemia. #### Causes - Decreased dietary intake of iron - Decreased absorption of iron (e.g., Coeliac disease) - Excessive blood loss (e.g., menstrual or GI bleeding) - Increased demand for red blood cells (e.g., pregnancy) #### Signs and Symptoms - Fatigue and dyspnoea - Koilonychia (spoon-shaped nails) - Pica (craving for specific foods/dirt) - Blue sclera #### Oral Findings - Pale oral mucosa - Depapillated atrophic tongue - Glossodynia (burning sensation) - Candidiasis and angular cheilitis - Aphthous-like ulcers A close-up photo of a spoon-shaped nail, illustrating koilonychia, a sign associated with iron-deficiency anaemia. This image is positioned next to the text describing the condition's signs and symptoms. A photo showing a depapillated atrophic tongue, a common oral finding in iron-deficiency anaemia. This image is placed adjacent to the section detailing oral manifestations of the condition. ## Plummer-Vinson(Patterson-Brown-Kelly) syndrome - Severe and chronic form of iron deficiency - Middle-aged female - Atrophic glossitis (smooth, atrophic and red tongue) - Pharyngeal and oesophageal webbing - Dysphagia (due to webbing) - Predisposition to post-cricoid and oral squamous cell carcinoma Plummer-Vinson syndrome (also known as Patterson-Brown-Kelly syndrome) is a severe and chronic form of iron deficiency. #### Clinical Characteristics - Typically affects middle-aged females. - **Atrophic glossitis:** Smooth, atrophic, and red tongue. - **Pharyngeal and oesophageal webbing:** Leads to dysphagia. - **Malignancy Risk:** Predisposition to post-cricoid and oral squamous cell carcinoma. # Dental management considerations - **Anaesthesia** - In poorly controlled anaemia: use LA without epinephrine because it may aggravate cardiac symptoms - **Anxiety/sedation** - Nitrous oxide can be used - GA avoided if the Hb level is 10g/dL - Iron deficiency in men may indicate an occult GI cancer; refer for evaluation #### Anaesthesia - In poorly controlled anaemia: Use local anaesthesia (LA) without epinephrine, as it may aggravate cardiac symptoms. #### Anxiety and Sedation - Nitrous oxide can be used. - General Anaesthesia (GA) should be avoided if the Hb level is below 10g/dL. #### Medical Referral - Iron deficiency in men may indicate an occult GI cancer; refer for further evaluation. Thalassemia - A hereditary haemoglobinopathy characterised by reduction in production of globin chains in the haemoglobin molecule - More prevalent in Mediterranean, African, Asian populations - Types - Alpha-thalassemia - Beta-thalassemia - Deletion or mutations in the alpha or beta globin genes - Decreased haemoglobin production and the formation of malformed RBCs Thalassemia is a hereditary haemoglobinopathy characterised by a reduction in the production of globin chains in the haemoglobin molecule. #### Epidemiology and Classification - More prevalent in Mediterranean, African, and Asian populations. - **Types:** - Alpha-thalassemia - Beta-thalassemia #### Pathogenesis - Caused by deletions or mutations in the alpha or beta globin genes. - Results in decreased haemoglobin production and the formation of malformed RBCs. # Clinical features - Severe jaundice, pallor, growth retardation, splenomegaly in the 1st year of life - Typical symptoms of anaemia - Bone expansion (result of intramedullary haematopoiesis) - Maxillary protrusion with spacing of teeth - Thin cortical plates and spongy marrow - Thin, widely spaced trabeculae - Hair-on-end appearance on a lateral skull radiograph <img src="https://i.imgur.com/9Y6ZzJl.png" alt="Clinical features images: patient face, dental X-rays, lateral skull radiograph"/> 8    #### Systemic Features - Severe jaundice, pallor, growth retardation, and splenomegaly (typically appearing in the 1st year of life). - Typical symptoms of anaemia. #### Skeletal and Radiographic Findings Bone expansion occurs as a result of intramedullary haematopoiesis: - Maxillary protrusion with spacing of teeth. - Thin cortical plates and spongy marrow. - Thin, widely spaced trabeculae. - "Hair-on-end" appearance on a lateral skull radiograph. A clinical photograph of a patient exhibiting maxillary protrusion, a feature associated with bone expansion due to intramedullary hematopoiesis, as described in the text. Dental X-rays showing thin cortical plates and spongy marrow, illustrating the bone changes related to intramedullary hematopoiesis. A lateral skull radiograph displaying the hair-on-end appearance, a characteristic finding of bone expansion in the skull. # Sickle cell anaemia - A hereditary haemoglobinopathy in which red cells contain an abnormal haemoglobin, HbS - Autosomal recessive disorder - More common in Mediterranean, African and Far East countries - A point mutation of beta-globin gene - Red cells become rigid and curved (sickle-shaped) - Deformed sickle cells are vulnerable to haemolysis - Newborn babies are screened for sickle cell status Sickle cell anaemia is a hereditary haemoglobinopathy in which red cells contain an abnormal haemoglobin, HbS. #### Pathogenesis - Autosomal recessive disorder. - More common in Mediterranean, African, and Far East countries. - Caused by a point mutation of the beta-globin gene. - Red cells become rigid and curved (sickle-shaped). - Deformed sickle cells are highly vulnerable to haemolysis. - Newborn babies are screened for sickle cell status. # Oral findings - Pallor or jaundice of oral mucosa - Widely spaced trabeculae - Step-ladder appearance of bone trabeculation in PA x-rays - Mandibular bone pain, osteomyelitis - Asymptomatic pulpal necrosis - Maxillary protrusion - Delayed eruption, dental hypoplasia <img src="https://i.imgur.com/5ZjKjZl.png" alt="X-ray image showing dental structures and bone trabeculation">  #### Clinical and Radiographic Findings - Pallor or jaundice of the oral mucosa. - Widely spaced trabeculae. - **Step-ladder appearance:** Characteristic bone trabeculation seen in periapical (PA) x-rays. - Mandibular bone pain and osteomyelitis. - Asymptomatic pulpal necrosis. - Maxillary protrusion. - Delayed eruption and dental hypoplasia. X-ray image showing dental structures and bone trabeculation, illustrating the step-ladder appearance of bone trabeculation in PA x-rays as mentioned in the surrounding text. # Causes of excessive bleeding and bruising - Vascular disorders - Capillary fragility - Hereditary haemorrhagic telangiectasia - Platelet disorders - Abnormal platelet number or function - Inability to develop a temporary clot - Coagulation disorders - Defects in coagulation - Inherited (e.g. von Willebrand’s disease, haemophilia) - Acquired (e.g. liver, anticoagulants) - Inability to form definitive clot - Fibrolytic disorders - Inability to destroy free plasmin  #### Vascular Disorders - Capillary fragility. - Hereditary haemorrhagic telangiectasia. #### Platelet Disorders - Abnormal platelet number or function. - Inability to develop a temporary clot. #### Coagulation Disorders - Defects in coagulation leading to an inability to form a definitive clot. - **Inherited:** e.g., von Willebrand’s disease, haemophilia. - **Acquired:** e.g., liver disease, anticoagulants. #### Fibrolytic Disorders - Inability to destroy free plasmin. The image displays a structured diagram outlining the causes of excessive bleeding and bruising, categorized into four main types: vascular disorders, platelet disorders, coagulation disorders, and fibrolytic disorders. Each category is further detailed with specific conditions, such as capillary fragility under vascular disorders and von Willebrand's disease under coagulation disorders. The layout uses bullet points and sub-bullets to organize the information hierarchically. # Assessing risk for bleeding - Bleeding problems in relatives (e.g. von Willebrand’s disease, haemophilia) - Bleeding after surgery, tooth extractions - Bleeding after trauma (cuts) - Medications may cause bleeding - Antiplatelets - Long term antibiotic therapy - Some herbal preparations - Disease associated bleeding tendencies - Leukaemia, thrombocytopenia - Chemotherapy - Advanced liver disease - Spontaneous bleeding from nose, mouth, GI #### Patient History - Bleeding problems in relatives (e.g., von Willebrand’s disease, haemophilia). - History of bleeding after surgery or tooth extractions. - Bleeding after trauma (cuts). - Spontaneous bleeding from the nose, mouth, or GI tract. #### Medications and Treatments - Antiplatelets. - Long-term antibiotic therapy. - Some herbal preparations. - Chemotherapy. #### Associated Medical Conditions - Leukaemia and thrombocytopenia. - Advanced liver disease. # Platelet disorders ## Thrombocytopenia - Low platelet levels in blood ### Cause - Decreased platelet production (e.g. bone marrow dysfunction) - Bone marrow infiltration by malignant cells (leukemia, myeloma, bone metastasis) - Toxic effects of chemotherapeutic drugs - Liver disease - Increased platelet consumption or destruction - Drug induced immunologic responses (heparin, quinidine, methyldopa) - Systemic disease: SLE and HIV infection - Vaccinations and viral infections - Immune (idiopathic) thrombocytopenic purpura (ITP) - Increased splenic sequestration (portal hypertension due to liver disease, tumour infiltration) ### Clinical evidence of thrombocytopenia not visible until platelet level falls below 100,00/µl (normal 150,000 to 450,000 µl) Thrombocytopenia is defined as low platelet levels in the blood. Clinical evidence is typically not visible until the platelet level falls below 100,000/µl (Normal range: 150,000 to 450,000/µl). #### Causes of Decreased Production - Bone marrow dysfunction or infiltration by malignant cells (leukaemia, myeloma, bone metastasis). - Toxic effects of chemotherapeutic drugs. - Liver disease. #### Causes of Increased Consumption or Destruction - Drug-induced immunologic responses (heparin, quinidine, methyldopa). - Systemic diseases: SLE and HIV infection. - Vaccinations and viral infections. - Immune (idiopathic) thrombocytopenic purpura (ITP). #### Other Causes - Increased splenic sequestration (portal hypertension due to liver disease, tumour infiltration). # Oral manifestations - Petechiae, ecchymosis - Spontaneous gingival bleeding - Postoperative bleeding ## Dental management considerations - History, clinical exam and tests (platelet count) - If needed, refer and consult a haematologist - Use local measures to control bleeding - Do not prescribe aspirin - Risk of infection in patients with bone marrow suppression (e.g. leukemia #### Oral Manifestations - Petechiae and ecchymosis. - Spontaneous gingival bleeding. - Postoperative bleeding. #### Dental Management Considerations - Obtain a thorough history, clinical exam, and relevant tests (platelet count). - Refer and consult a haematologist if necessary. - Use local measures to control bleeding. - **Contraindication:** Do not prescribe aspirin. - Be aware of the risk of infection in patients with bone marrow suppression (e.g., leukaemia). | Product | Description | | --- | --- | | Gauze | 2″×2″ sterile gauze pads; place over the wound and have the patient put pressure on it by closing or finger pressure | | Surgicel® | A cellulose-based product (oxidized regenerated cellulose); exerts physical effect rather than physiologic; swells on contact with blood with resulting pressure adding to hemostasis; after 24-48 hours, it becomes gelatinous; can be left in place or removed | | Avitene® | A collagen-based products (microfibrillar collagen hemostat); attracts platelets and triggers aggregation in fibrous mass | | Gelfoam® | A gelatin-based products; absorbable gelatin sponge | | Tranexamic acid | Tranexamic acid is an antifibrinolytic agent; works as a competitive inhibitor of plasminogen activation; (available only in Europe as 4.8% oral mouthwash; as Cyklokapron® or Lysteda® tablet and Cyklokapron® injection in the USA) | | ε-Aminocaproic acid (EACA) | EACA (Amicar®) is an antifibrinolytic agent; works as a competitive inhibitor of plasminogen activation; used as a rinse (25% Amicar® syrup) | | Thrombostat® | Topical thrombin; converts fibrinogen to fibrin | | Other local measures include atraumatic/minimally traumatic surgery, and precise suturing technique | |  #### Physical and Mechanical Agents - **Gauze:** 2″×2″ sterile pads; applied with pressure (closing or finger pressure). - **Surgicel®:** Oxidized regenerated cellulose; exerts a physical effect by swelling on contact with blood; becomes gelatinous after 24-48 hours. - **Gelfoam®:** Absorbable gelatin sponge. - **Atraumatic Technique:** Minimally traumatic surgery and precise suturing. #### Physiological and Chemical Agents - **Avitene®:** Microfibrillar collagen hemostat; attracts platelets and triggers aggregation. - **Thrombostat®:** Topical thrombin; converts fibrinogen to fibrin. #### Antifibrinolytic Agents - **Tranexamic acid:** Competitive inhibitor of plasminogen activation (available as 4.8% mouthwash in Europe; tablets or injections in the USA). - **ε-Aminocaproic acid (EACA/Amicar®):** Competitive inhibitor of plasminogen activation; used as a rinse (25% syrup). A table titled "Topical Hemostatic and Local Antifibrinolytic Agents used to Control Bleeding" that lists various products and their descriptions. The table includes columns for "Product" and "Description," detailing agents such as Gauze, Surgicel®, Avitene®, Gelfoam®, Tranexamic acid, ε-Aminocaproic acid (EACA), Thrombostat®, and other local measures. Each product's description explains its composition, mechanism of action, and application method. # Platelet function disorders - Inherited disorders - Von Willebrand’s disease (may have secondary factor VIII deficiency) - Acquired platelet dysfunction - Drug induced - e.g. aspirin, clopidogrel - NSAIDs, beta-lactum antibiotics (penicillin), calcium channel blocking drugs, phenytoin - End-stage renal disease - Uraemia (high level of waste products (urea) in the blood due to kidney failure) - Circulating toxins can impair platelet function - Alcohol ingestion #### Inherited Disorders - **Von Willebrand’s disease:** May also involve a secondary factor VIII deficiency. #### Acquired Platelet Dysfunction - **Drug-induced:** Aspirin, clopidogrel, NSAIDs, beta-lactam antibiotics (penicillin), calcium channel blockers, and phenytoin. - **End-stage renal disease:** Uraemia (high urea levels) can result in circulating toxins that impair platelet function. - **Alcohol ingestion.** # Von Willebrand Disease - Von Willebrand disease is the most common inherited bleeding disorder - Characterised by deficient or defective von Willebrand factor (vWF) - Caused by an inherited gene mutation on chromosome 12 - Both males and females are affected - vWF - serves as a carrier protein for Factor VIII - Affected patients experience platelet dysfunction and deficiency of Factor VIII - Clinical features - Ecchymoses and nose bleeds common findings - Prolonged bleeding after tooth extraction - Severe forms: haemarthroses Von Willebrand disease is the most common inherited bleeding disorder, caused by an inherited gene mutation on chromosome 12 affecting both males and females. #### Pathophysiology - Characterised by deficient or defective von Willebrand factor (vWF). - vWF serves as a carrier protein for Factor VIII. - Patients experience both platelet dysfunction and Factor VIII deficiency. #### Clinical Features - Common findings: Ecchymoses and nose bleeds. - Prolonged bleeding after tooth extraction. - Severe forms may present with haemarthroses. # Coagulation disorders ## Hereditary - Von Willebrand’s disease - Haemophilia - Haemophilia A - Factor VIII deficiency - Haemophilia B - Factor IX deficiency ## Acquired - Anticoagulants - Oral anticoagulants - Warfarin - Heparin therapy - Viral hepatitis - Alcoholism - Vitamin K deficiency - Long term use of broad-spectrum antibiotics - Malabsorption  #### Hereditary Disorders - Von Willebrand’s disease - **Haemophilia:** - Haemophilia A (Factor VIII deficiency) - Haemophilia B (Factor IX deficiency) #### Acquired Disorders - **Anticoagulants:** Warfarin and Heparin therapy. - **Liver Disease:** Viral hepatitis and alcoholism. - **Vitamin K Deficiency:** Caused by malabsorption or long-term use of broad-spectrum antibiotics. A hierarchical diagram categorizing coagulation disorders into hereditary and acquired types. The hereditary category includes Von Willebrand's disease and haemophilia, with subcategories for Haemophilia A (Factor VIII deficiency) and Haemophilia B (Factor IX deficiency). The acquired category lists anticoagulants (including warfarin), heparin therapy, viral hepatitis, alcoholism, vitamin K deficiency (with long-term antibiotic use as a cause), and malabsorption. # Haemophilia A - X-linked recessive disorder characterized by factor VIII deficiency - Primarily affects males, females are usually carriers - Normal haemostasis requires 30% factor VIII activity ## Mild haemophilia - Factor VIII level between 5-30% - Patients asymptomatic ## Moderate haemophilia - Factor VIII level between 1-5% ## Severe haemophilia - Factor VIII level less than 1% Haemophilia A is an X-linked recessive disorder characterized by factor VIII deficiency. It primarily affects males, while females are usually carriers. Normal haemostasis requires at least 30% factor VIII activity. #### Severity Classification - **Mild haemophilia:** Factor VIII level between 5-30%; patients are often asymptomatic. - **Moderate haemophilia:** Factor VIII level between 1-5%. - **Severe haemophilia:** Factor VIII level less than 1%. # Clinical features - Ecchymoses, hemarthrosis, dissecting haematomas are common findings - Oral findings - Persistent bleeding after dental surgery - Bleeding after tooth extraction may be first evidence of mild haemophilia - Liver clots and haematomas - Spontaneous mucosal or gingival bleeding - Hemarthrosis of TMJ is a rare finding <img src="https://i.imgur.com/1a.png" alt="Ecchymosis on arm"> <img src="https://i.imgur.com/2b.png" alt="Bleeding after tooth extraction"> <img src="https://i.imgur.com/3c.png" alt="Spontaneous gingival bleeding">    #### General and Oral Findings - Common findings: Ecchymoses, hemarthrosis, and dissecting haematomas. - Persistent bleeding after dental surgery. - Bleeding after tooth extraction (may be the first evidence of mild haemophilia). - Formation of liver clots and haematomas. - Spontaneous mucosal or gingival bleeding. - Hemarthrosis of the TMJ (rare finding). A photo showing ecchymosis on an arm, illustrating a common clinical finding of bruising associated with bleeding disorders. A photo depicting bleeding after tooth extraction, highlighting an oral finding that may be the first evidence of mild hemophilia. A photo showing spontaneous gingival bleeding, illustrating a mucosal bleeding manifestation commonly seen in bleeding disorders. # Haemophilia B (Christmas disease) - Sex-linked recessive disorder characterised by Factor IX deficiency - Clinical features are identical to Haemophilia A - Classified as mild, moderate, or severe - 20-45% of haemophilia cases are severe - Lab tests: prolonged PTT (partial thromboplastin time) and Factor IX deficiency - Medical management: Factor IX replacement  Haemophilia B, also known as Christmas disease, is a sex-linked recessive disorder characterised by Factor IX deficiency. #### Clinical Profile - Clinical features are identical to Haemophilia A. - Classified as mild, moderate, or severe (20-45% of cases are severe). #### Diagnosis and Management - **Lab tests:** Prolonged PTT (partial thromboplastin time) and confirmed Factor IX deficiency. - **Medical management:** Factor IX replacement therapy. A close-up clinical photo showing the oral cavity of a patient with haemophilia B, displaying extensive bleeding and bruising around the teeth and gums, illustrating the severity of bleeding complications associated with the disorder. # Dental management for patients on Warfarin - Determine the reason for anticoagulant therapy - Bleeding - Confirm INR level - INR ideally taken within 72 hours of the scheduled dental procedure - Consult with the patient’s physician if needed - If INR is 3.5 or less - Minor procedures can be performed with local haemostatic measures - If the INR is greater than 3.5 - Consult the physician - Delay the dental procedure by 3-5 days, confirm INR level - INR should be less than 3.0 for major oral surgery - If post-operative bleeding is uncontrollable, Vitamin K or fresh frozen plasma may be used #### Pre-operative Assessment - Determine the reason for anticoagulant therapy. - Confirm the INR level, ideally within 72 hours of the scheduled procedure. - Consult with the patient’s physician if necessary. #### Clinical Guidelines based on INR - **INR ≤ 3.5:** Minor procedures can be performed using local haemostatic measures. - **INR > 3.5:** Consult the physician; delay the procedure by 3-5 days and re-confirm the INR level. - **Major Oral Surgery:** INR should be less than 3.0. #### Emergency Measures - If post-operative bleeding is uncontrollable, Vitamin K or fresh frozen plasma may be used. # Leukaemia - Cancer of WBCs that affects the bone marrow and circulating blood - Involves exponential proliferation of clonal or lymphoid cell - Acute leukaemia - Sudden onset and rapid course - Immature, undifferentiated WBCs - Chronic Leukaemia - Slower onset - More mature, functional cells - Types: ALL, AML, CLL, CML Leukaemia is a cancer of the white blood cells (WBCs) that affects the bone marrow and circulating blood, involving the exponential proliferation of clonal or lymphoid cells. #### Classification - **Acute Leukaemia:** Sudden onset and rapid course; involves immature, undifferentiated WBCs. - **Chronic Leukaemia:** Slower onset; involves more mature, functional cells. - **Types:** ALL, AML, CLL, CML. # Oral manifestations of leukaemia - Mucosal pallor (an important sign in children) - Gingival bleeding, petechiae or purpura - Oral ulcers (herpetic, neutropenic or drug-induced) - Oral infections (e.g. candidiasis, CMV) - Localised or generalised gingival enlargement - Caused by leukemic infiltrates - Gingiva is boggy, bleeds easily - Myeloid sarcoma - Localised mass of leukemic cells - Involve maxilla, palate, gingiva, tongue, oral mucosa - Cervical lymphadenopathy     #### Clinical Signs - Mucosal pallor (important sign in children). - Gingival bleeding, petechiae, or purpura. - Oral ulcers (herpetic, neutropenic, or drug-induced). - Oral infections (e.g., candidiasis, CMV). - Cervical lymphadenopathy. #### Specific Pathologies - **Gingival Enlargement:** Localised or generalised; caused by leukemic infiltrates. Gingiva appears boggy and bleeds easily. - **Myeloid Sarcoma:** A localised mass of leukemic cells that can involve the maxilla, palate, gingiva, tongue, or oral mucosa. Close-up photo showing gingival bleeding and petechiae in a patient with leukemia, illustrating mucosal pallor and gingival enlargement as described in the text. Photo of the tongue showing purpuric lesions, demonstrating oral manifestations such as petechiae and purpura associated with leukemia. Photo of a patient with severe oral involvement, including ulceration and gingival enlargement, consistent with leukemic infiltration and neutropenic ulcers. Photo of the oral cavity showing generalized gingival enlargement and inflammation, likely due to leukemic infiltrates, as mentioned in the text. ```markdown # Lymphoma - Cancer of the lymphoid organs and tissues that present as discrete masses - Main types: Hodgkin and Non-Hodgkin lymphomas ## Hodgkin Lymphoma (HL) - HL is a B lymphocyte neoplasm - Contains a characteristic tumour cell - Reed-Sternberg cell (large, bi-nucleated tumour cell) - Most common in adolescents and young adults - Has a bimodal incidence pattern: 20-30 and 50-70 years - EBV linked to 40% of cases - Typically manifest as painless firm enlarged lymph nodes (rubbery consistency) - Mediastinal and cervical lymph nodes affected - Oral involvement is rare - Pruritus, fatigue, fever, weight loss, night sweats are common ``` <img src="https://i.imgur.com/1a.png" alt="Microscopic view of Reed-Sternberg cells in Hodgkin lymphoma tissue section."> <img src="https://i.imgur.com/2b.png" alt="Clinical image showing skin rash, possibly related to systemic symptoms of lymphoma."> ```   Hodgkin Lymphoma (HL) is a B lymphocyte neoplasm that presents as discrete masses in lymphoid organs. #### Pathophysiology and Epidemiology - Contains the characteristic **Reed-Sternberg cell** (large, bi-nucleated tumour cell). - Most common in adolescents and young adults (bimodal incidence: 20-30 and 50-70 years). - EBV is linked to 40% of cases. #### Clinical Presentation - Typically manifests as painless, firm, enlarged lymph nodes with a rubbery consistency (commonly mediastinal and cervical). - Oral involvement is rare. - Systemic symptoms: Pruritus, fatigue, fever, weight loss, and night sweats. Microscopic view of Reed-Sternberg cells in Hodgkin lymphoma tissue section, showing large, bi-nucleated tumor cells with prominent nucleoli, characteristic of Hodgkin lymphoma. Clinical image showing skin rash, possibly related to systemic symptoms of lymphoma, with erythematous lesions on the skin, illustrating a potential cutaneous manifestation of the disease. Non-Hodgkin lymphoma (NHL) - Large group of lymphoproliferative disorders derived from B, T and natural killer cells - B-cell proliferation accounts for 85-90% of cases - Can occur at any age (median age at the time of diagnosis is 67 years) - Causative agents include genetic factors, infectious agents, autoimmune diseases (Sjögren syndrome,) and immunodeficiency states (AIDS) - Involvement can be nodal or extra nodal - Painless, firm enlarged cervical lymph nodes - Oral submucosal mass may or may not be ulcerated - Salivary glands, those affected by Sjögren syndrome - Jaw bones in African children with Burkitt's Lymphoma   Non-Hodgkin lymphoma (NHL) is a large group of lymphoproliferative disorders derived from B, T, and natural killer cells (B-cell proliferation accounts for 85-90% of cases). #### Risk Factors and Age - Can occur at any age (median age at diagnosis is 67 years). - Causative agents: Genetic factors, infectious agents, autoimmune diseases (e.g., Sjögren syndrome), and immunodeficiency states (e.g., AIDS). #### Clinical Presentation - Involvement can be nodal (painless, firm enlarged cervical lymph nodes) or extra-nodal. - **Oral Findings:** - Oral submucosal mass (may or may not be ulcerated). - Involvement of salivary glands (especially those affected by Sjögren syndrome). - Jaw bone involvement in African children with Burkitt's Lymphoma. Close-up photograph showing an oral submucosal mass in the upper palate, consistent with non-Hodgkin lymphoma involvement, with a reddish, swollen appearance. Photograph depicting a large, firm mass in the oral cavity, likely a submucosal tumor, associated with non-Hodgkin lymphoma, with visible teeth and surrounding tissue. Multiple myeloma • Malignant neoplasm composed of plasma cells which occurs as disseminates disease involving many bones • Clinical features • Men over 50 years, persistent bone pain • Multiple osteolytic bone lesions • Multiple punched-out lesions or mottled areas on the radiograph • Vertebrae, sternum, ribs and pelvic bones commonly affected • Osteolytic lesions of the jaws in 30% of patients • Lead to serum hypercalcaemia • May cause pathological fracture • Fever and recurrent infections (result of neutropenia) • Proteinuria and renal failure • Amyloid deposition in various tissues (e.g. heart liver, liver, nervous tissue)  Multiple myeloma is a malignant neoplasm composed of plasma cells, occurring as a disseminated disease involving many bones. #### Clinical Features - Typically affects men over 50 years; presents with persistent bone pain. - **Skeletal Involvement:** Multiple osteolytic "punched-out" lesions or mottled areas on radiographs. Commonly affects vertebrae, sternum, ribs, and pelvic bones. - **Jaw Involvement:** Osteolytic lesions of the jaws occur in 30% of patients. - **Systemic Complications:** - Serum hypercalcaemia and potential pathological fractures. - Fever and recurrent infections due to neutropenia. - Proteinuria and renal failure. - Amyloid deposition in various tissues (heart, liver, nervous tissue). A radiographic image showing multiple punched-out lesions in the skull, consistent with osteolytic bone lesions seen in multiple myeloma. The image displays a characteristic mottled appearance of the bone structure, with areas of radiolucency indicating bone destruction. # Oral manifestations - Radiographs of jaws may show “punched-out” lesions - Can cause bone pain, paraesthesia and cortical enlargement - This could be the initial manifestation of the disease - Amyloid deposition in the tongue cause macroglossia and pain - Medication-related osteonecrosis of the jaw (MRONJ) - Potential serious complication of long-term bisphosphonates - Commonly observed in the mandible - Petechiae, pallor, susceptibility to bleeding and infections <img src="https://i.imgur.com/7Q5Xq7l.png" alt="Radiograph showing 'punched-out' lesions in the jaw"> <img src="https://i.imgur.com/8Z0jJ7m.png" alt="Macroscopic view of a swollen, reddened tongue">   #### Radiographic and Oral Findings - **"Punched-out" lesions:** May cause bone pain, paraesthesia, and cortical enlargement; can be the initial manifestation of the disease. - **Macroglossia:** Caused by amyloid deposition in the tongue, leading to pain. - **Haematological signs:** Petechiae, pallor, and increased susceptibility to bleeding and infections. #### Treatment Complications - **MRONJ (Medication-related osteonecrosis of the jaw):** A potentially serious complication of long-term bisphosphonate therapy, commonly observed in the mandible. Radiograph showing 'punched-out' lesions in the jaw, which are associated with bone pain, paraesthesia, and cortical enlargement, potentially representing the initial manifestation of a disease. Macroscopic view of a swollen, reddened tongue, illustrating macroglossia caused by amyloid deposition, which can lead to pain and functional impairment. IMMUNODEFICIENCY Immunodeficiency refers to a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. # Primary immunodeficiency - Genetically based - Predominantly B or T-cell defects or a combination or due to a selective immunodeficiency (IgA deficiency) - Result in life-threatening conditions - Affected individuals tend to die young as result of recurrent infection - Candida infections are often predominant in these patients - More susceptible to periodontal infections #### Characteristics of Primary Immunodeficiency - Genetically based. - Predominantly involves B-cell or T-cell defects, a combination of both, or selective immunodeficiencies (e.g., IgA deficiency). - Results in life-threatening conditions. - Affected individuals tend to die young as a result of recurrent infection. #### Clinical Manifestations - Candida infections are often predominant in these patients. - Patients are more susceptible to periodontal infections. # Secondary immunodeficiency - Malignancies - Leukaemia, lymphoma, multiple myeloma - Medications - Corticosteroids and immunosuppressants; chemotherapy - Malnutrition - Autoimmune disorders - Radiation - Diabetes mellitus - Chronic renal failure - Infections (HIV, TB) Secondary immunodeficiency can arise from various underlying conditions and external factors: - **Malignancies** - Leukaemia, lymphoma, multiple myeloma - **Medications** - Corticosteroids and immunosuppressants - Chemotherapy - **Health and Lifestyle Factors** - Malnutrition - Autoimmune disorders - Diabetes mellitus - Chronic renal failure - **Environmental and Infectious Factors** - Radiation - Infections (e.g., HIV, TB) Human immunodeficiency virus infection - RNA retrovirus infection - Spread through: - sexual contact - parenteral exposure to blood - mother to foetus - Immune deficiency due to damage to CD4 T-lymphocytes - Predisposition to infections with: - Viruses and virally induced malignancies - Fungi - Mycobacteria - Autoimmune disease - Neurological damage  #### Pathophysiology and Transmission - Caused by an RNA retrovirus infection. - Spread through: - Sexual contact - Parenteral exposure to blood - Mother to foetus - Immune deficiency is due to damage to CD4 T-lymphocytes. #### Predisposition to Complications Infected individuals are predisposed to: - Viruses and virally induced malignancies - Fungi - Mycobacteria - Autoimmune disease - Neurological damage Two clinical photos showing oral lesions associated with human immunodeficiency virus infection. The top image displays a white, ulcerated lesion on the tongue, while the bottom image shows multiple lesions on the gums and inner cheek, indicative of opportunistic infections in immunocompromised patients. ```html <table> <thead> <tr> <th>Stages</th> <th>Description</th> </tr> </thead> <tbody> <tr> <td>Stage I</td> <td>Seroconversion illness (2-3 weeks)<br>Fever, malaise, lymphadenopathy, pharyngitis, mouth ulcers<br>Antibodies develop within 3-6 months</td> </tr> <tr> <td>Stage II</td> <td>Asymptomatic stage: (chronic phase ~10 years)</td> </tr> <tr> <td>Stage III</td> <td>Persistent generalized lymphadenopathy: (~ 10 years)</td> </tr> <tr> <td>Stage IV (A-E)</td> <td>Symptomatic stage (diseases involving entire body, neurological disease, secondary infectious disease, secondary cancers, other conditions</td> </tr> </tbody> </table> ```  #### Clinical Progression Stages 1. **Stage I: Seroconversion Illness** - Occurs within 2-3 weeks. - Symptoms: Fever, malaise, lymphadenopathy, pharyngitis, mouth ulcers. - Antibodies typically develop within 3-6 months. 2. **Stage II: Asymptomatic Stage** - Chronic phase lasting approximately 10 years. 3. **Stage III: Persistent Generalized Lymphadenopathy** - Lasts approximately 10 years. 4. **Stage IV (A-E): Symptomatic Stage** - Diseases involving the entire body. - Includes neurological disease, secondary infectious disease, secondary cancers, and other conditions. A table titled 'Classification of stages of HIV infection (Centre for Disease Control, USA)' that outlines the progression of HIV infection through four stages. Stage I describes seroconversion illness with symptoms like fever, malaise, lymphadenopathy, pharyngitis, and mouth ulcers, with antibodies developing within 3-6 months. Stage II is the asymptomatic chronic phase lasting approximately 10 years. Stage III involves persistent generalized lymphadenopathy for about 10 years. Stage IV (A-E) represents the symptomatic stage, characterized by diseases affecting the entire body, neurological disease, secondary infections, secondary cancers, and other conditions. # Classification of oral lesions in HIV | Group I | Lesions strongly associated with HIV infections | HIV associated candidosis | | --- | --- | --- | | Group II | Lesions less commonly associated with HIV infection | HIV associated CMV ulcer | | Group III | Lesions possibly associated with HIV infection | HIV associated wart |    #### Classification of Oral Lesions - **Group I: Lesions strongly associated with HIV infections** - Example: HIV-associated candidosis - **Group II: Lesions less commonly associated with HIV infection** - Example: HIV-associated CMV ulcer - **Group III: Lesions possibly associated with HIV infection** - Example: HIV-associated wart A photograph of an oral lesion showing white patches on the tongue, classified as Group I, which are strongly associated with HIV infections, specifically HIV-associated candidosis. A photograph of an oral lesion with a large ulcerated area on the tongue, classified as Group II, which are less commonly associated with HIV infection, specifically an HIV-associated CMV ulcer. A photograph of an oral lesion showing a small, raised growth on the palate, classified as Group III, which are possibly associated with HIV infection, specifically an HIV-associated wart. # Oral Lesions in HIV disease | Candidiasis | | --- | | Hairy leukoplakia | | Kaposi’s sarcoma | | Gingival and periodontal disease | | Ulcers | | Other orofacial conditions |  Common oral manifestations observed in HIV disease include: - Candidiasis - Hairy leukoplakia - Kaposi’s sarcoma - Gingival and periodontal disease - Ulcers - Other orofacial conditions A table listing various oral lesions associated with HIV disease, including Candidiasis, Hairy leukoplakia, Kaposi's sarcoma, Gingival and periodontal disease, Ulcers, and Other orofacial conditions. The table is structured with alternating light gray and white rows for readability. # Hairy Leukoplakia ## Clinical Features - White patch which cannot be removed - Vertical white folds on the lateral aspects of tongue - Associated with EBV ## Additional Characteristics - Lesion not premalignant - Usually superimposed by candida - Common in patients with late-stage HIV infection - Development may herald onset of AIDS ## Diagnostic Information - Diagnosis: Clinical - Biopsy: ballooned cells with perinuclear vacuoles, swollen cells contain EBV    #### Clinical Features - Presents as a white patch which cannot be removed. - Characterized by vertical white folds on the lateral aspects of the tongue. - Associated with Epstein-Barr Virus (EBV). #### Additional Characteristics - The lesion is not premalignant. - Usually superimposed by Candida. - Common in patients with late-stage HIV infection. - Development may herald the onset of AIDS. #### Diagnostic Information - **Diagnosis:** Primarily clinical. - **Biopsy:** Shows ballooned cells with perinuclear vacuoles; swollen cells contain EBV. Clinical photograph showing a white patch on the lateral aspect of the tongue, consistent with hairy leukoplakia, associated with EBV infection. Oral photograph displaying vertical white folds on the lateral surface of the tongue, a characteristic feature of hairy leukoplakia, often seen in late-stage HIV infection. Microscopic image from a biopsy showing ballooned cells with perinuclear vacuoles, indicative of EBV infection in the context of hairy leukoplakia. Kaposi’s Sarcoma Most common malignancy in HIV patients Involves skin and mucosal surfaces Tip of the nose frequent facial site Caused by human herpes type 8 Common in homosexuals, can occur in all risk groups Arises from vascular endothelial cells Hard palate and gingiva are common sites Presents as a reddish-purple patches Becomes nodular and ulcerate Diagnosis must be supported by biopsy    #### Overview - The most common malignancy in HIV patients. - Caused by Human Herpesvirus type 8 (HHV-8). - Arises from vascular endothelial cells. - Common in homosexuals, though it can occur in all risk groups. #### Clinical Presentation - Involves skin and mucosal surfaces. - The tip of the nose is a frequent facial site. - Common oral sites include the hard palate and gingiva. - Presents as reddish-purple patches that may become nodular and ulcerate. #### Diagnosis - Clinical suspicion must be supported by biopsy. A photo showing reddish-purple lesions on the skin, consistent with Kaposi's Sarcoma, located on the leg of a patient. This image illustrates the common presentation of the malignancy on skin surfaces. A photo of the oral cavity showing a reddish-purple lesion on the hard palate, demonstrating a common site for Kaposi's Sarcoma in the mouth, which can involve mucosal surfaces. A photo of the oral cavity displaying a reddish-purple patch on the gingiva, which becomes nodular and ulcerated, illustrating the clinical presentation of Kaposi's Sarcoma in the mouth. ```markdown # HIV-associated periodontal diseases | **Linear gingival erythema** | |---| | Red band involving free gingival margins Not related to accumulation of dental plaque | **Punched-out ulceration of the interdental papillae** | |---| | **Necrotizing ulcerative gingivitis** | **Necrosis of gingival and periodontal tissues** | |---| | Sometimes exposure and sequestration of alveolar bone **Destructive periodontitis** ```    #### Linear Gingival Erythema - Characterized by a red band involving the free gingival margins. - Not related to the accumulation of dental plaque. #### Necrotizing Conditions - **Necrotizing Ulcerative Gingivitis:** Features punched-out ulceration of the interdental papillae. - **Destructive Periodontitis:** Involves necrosis of gingival and periodontal tissues, sometimes resulting in exposure and sequestration of alveolar bone. A clinical photograph showing linear gingival erythema, characterized by a red band involving the free gingival margins, with no apparent accumulation of dental plaque. A clinical photograph illustrating punched-out ulceration of the interdental papillae, a feature of necrotizing ulcerative gingivitis, with visible tissue destruction. A clinical photograph depicting necrosis of gingival and periodontal tissues, with exposure and sequestration of alveolar bone, characteristic of destructive periodontitis. Lymphoma Oral lesions: soft tissue enlargement or ulcerative lesion of gingiva Increased incidence of NHL Some associated with EBV   #### Clinical Presentation - Oral lesions present as soft tissue enlargement or ulcerative lesions of the gingiva. #### Pathological Associations - Increased incidence of Non-Hodgkin Lymphoma (NHL). - Some cases are associated with Epstein-Barr Virus (EBV). A photo showing an oral lesion with soft tissue enlargement of the gingiva, characterized by a swollen, reddish mass with visible teeth and a yellowish lesion on the gum tissue. A photo depicting a large, ulcerative lesion in the oral cavity, with a prominent red mass on the gum tissue and surrounding inflamed tissue, illustrating a severe oral lesion. ```markdown Acquired immunodeficiency syndrome (AIDS) - AIDS is the final stage of HIV disease - CD4 cell count: <200 cells/mm³ - CD4 cell %: <14% - Highly active antiretroviral therapy (HAART) has improved the quality and length of survival for many 40 ``` - AIDS is the final stage of HIV disease. - **Clinical Markers:** - CD4 cell count: <200 cells/mm³ - CD4 cell %: <14% - Highly active antiretroviral therapy (HAART) has significantly improved the quality and length of survival for many patients. # HIV Diagnosis - Diagnosis is clear: patient with obvious lesions for e.g., HL, candidiasis, Kaposi’s sarcoma - Serological confirmation is necessary (enzyme linked immunosorbent assay) - HIV P24 antibody confirmed by Western Blot - Polymerase chain reaction (PCR) to detect HIV RNA #### Clinical and Laboratory Diagnosis - Diagnosis may be clear when a patient presents with obvious lesions such as Hairy Leukoplakia (HL), candidiasis, or Kaposi’s sarcoma. - **Serological Confirmation:** Necessary via Enzyme-Linked Immunosorbent Assay (ELISA). - **Confirmatory Testing:** HIV P24 antibody confirmed by Western Blot. - **Viral Detection:** Polymerase Chain Reaction (PCR) is used to detect HIV RNA. # Key points: HIV infection - Caused by retrovirus - Transmitted sexually, IV drug abuse, blood & blood products - Progressive deterioration of cell-mediated immunity - Oral signs and symptoms may be the initial manifestation - Oral candidiasis most prevalent oral lesion - Hairy leukoplakia may indicate progression to AIDS - Kaposi’s sarcoma and lymphomas often in the oral regions - Neurological and psychological disorders - Death mainly due to opportunistic infections 42 #### Summary of HIV Infection - Caused by a retrovirus. - Transmitted sexually, through IV drug abuse, and via blood & blood products. - Characterized by progressive deterioration of cell-mediated immunity. - Oral signs and symptoms may be the initial manifestation of the disease. - Oral candidiasis is the most prevalent oral lesion. - Hairy leukoplakia may indicate progression to AIDS. - Kaposi’s sarcoma and lymphomas often occur in the oral regions. - Associated with neurological and psychological disorders. - Death is mainly due to opportunistic infections. ```markdown Dentist’s role: management of patients with HIV infection | Refer to a specialist if diagnosis has not been made | | --- | | Understand the disease and management | | Oral health care; in particular to avoid causes of infection or pain | | Avoid needle stick accidents, avoid surgery where possible, treat xerostomia | | Oral health education of the patient | | Treat diagnosis with confidentiality | | Avoid drug interactions with antiretroviral agents | | Strict adherence to infection control measures | ```  #### Responsibilities and Clinical Guidelines - **Referral:** Refer to a specialist if a diagnosis has not yet been made. - **Knowledge:** Understand the disease progression and management strategies. - **Clinical Care:** - Provide oral health care, specifically to avoid causes of infection or pain. - Avoid needle stick accidents. - Avoid surgery where possible. - Treat xerostomia. - **Patient Education:** Provide oral health education to the patient. - **Ethics and Safety:** - Treat the diagnosis with strict confidentiality. - Avoid drug interactions with antiretroviral agents. - Maintain strict adherence to infection control measures. A table outlining the dentist's role in managing patients with HIV infection, listing key responsibilities such as referring to specialists, understanding the disease, providing oral health care, avoiding needle stick accidents, educating patients, maintaining confidentiality, avoiding drug interactions, and adhering to infection control measures. [^1]: Original PDF page 1: [[L21 haematological disease and immunodeficiency.pdf#page=1|L21 haematological disease and immunodeficiency, p.1]] [^2]: Original PDF page 2: [[L21 haematological disease and immunodeficiency.pdf#page=2|L21 haematological disease and immunodeficiency, p.2]] [^3]: Original PDF page 3: [[L21 haematological disease and immunodeficiency.pdf#page=3|L21 haematological disease and immunodeficiency, p.3]] [^4]: Original PDF page 4: [[L21 haematological disease and immunodeficiency.pdf#page=4|L21 haematological disease and immunodeficiency, p.4]] [^5]: Original PDF page 5: [[L21 haematological disease and immunodeficiency.pdf#page=5|L21 haematological disease and immunodeficiency, p.5]] [^6]: Original PDF page 6: [[L21 haematological disease and immunodeficiency.pdf#page=6|L21 haematological disease and immunodeficiency, p.6]] [^7]: Original PDF page 7: [[L21 haematological disease and immunodeficiency.pdf#page=7|L21 haematological disease and immunodeficiency, p.7]] 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and immunodeficiency, p.41]] [^42]: Original PDF page 42: [[L21 haematological disease and immunodeficiency.pdf#page=42|L21 haematological disease and immunodeficiency, p.42]] [^43]: Original PDF page 43: [[L21 haematological disease and immunodeficiency.pdf#page=43|L21 haematological disease and immunodeficiency, p.43]]