Immunocompromised PDF

2.4 IMMUNOCOMPRIMISED - **To consider the consequences of neutropenia, humoral and cell mediated immunodeficiency and deficiencies of the complement system** Agammaglobulimaemia: - 85% = brutons disease (X-linked -\> only affects males) - 15% autosomal recessive Hyper IgM syndrom...

2.4 IMMUNOCOMPRIMISED - **To consider the consequences of neutropenia, humoral and cell mediated immunodeficiency and deficiencies of the complement system** Agammaglobulimaemia: - 85% = brutons disease (X-linked -\> only affects males) - 15% autosomal recessive Hyper IgM syndrome: - B cells fail to switch from IgM production T cell deficiencies: SCID: - May affect T, B, NK cells - Most common = gamma chain of IL receptors; IL-2 = proliferation, IL-4 = B cell class switching, IL-7 = anti-apoptotic, IL-15 = NK cell development - sometimes affects downstream signalling molecules of IL receptors - requires BM transplant -\> fatal if untreated Di George syndrome: (22q11 deletion) - thymic aplasia -\> varying levels of T cell immunodeficiency - parathyroid underdeveloped or absent - higher risk of infection (limited t cell mediated/ T-dependant B cell) - connective tissue issues - occasional mental health problems Neutropenia: - low neutrophil count - caused by autoimmune destruction - bone marrow malignany - chemo - B12/folate/iron deficiency - Phenytoin - Chloramphenicol - Alcohol - If below \ - **To distinguish between primary and secondary immunodeficiency** **Primary: (congenital / inherited)** - Combined immunodeficiencies (T and B cell defects) / with associated or syndromic features - Predominantly Ig deficiencies - Complement deficiency - Congenital defects of phagocyte number, function, or both. - Auto-inflammatory disorders - Defects in innate immunity - Phenocopies of primary immunodeficiencies (presenting as inherited disorders but arising from acquired mechanisms). **Secondary: (acquired)** - Disease: Infection (HIV, malaria), malnutrition, cancer, diabetes mellitus - Drug induced immunosuppression - **To investigate congenital, acquired and iatrogenic conditions which may lead to immunodeficiency** **1. Congenital Immunodeficiency (Primary Immunodeficiency Disorders)** - **Definition**: Inherited disorders caused by genetic mutations that impair the development or function of immune system components. - **Examples**: - **Severe Combined Immunodeficiency (SCID)**: A defect in both T cells and B cells, leading to severe susceptibility to infections. - **X-linked Agammaglobulinemia (XLA)**: Lack of mature B cells due to a mutation in the *BTK* gene. - **DiGeorge Syndrome**: A chromosomal deletion affecting the thymus, leading to T cell deficiencies. - **Chronic Granulomatous Disease (CGD)**: Defective phagocytes that cannot produce reactive oxygen species to kill pathogens. - **Complement Deficiencies**: Defects in complement proteins impair the innate immune response. - **Investigation**: - Genetic testing (e.g., for mutations in *BTK*, *ADA*, *RAG1/2*). - Immune profiling (e.g., flow cytometry for T, B, and NK cells). - Functional assays (e.g., oxidative burst tests for CGD). **2. Acquired Immunodeficiency** - **Definition**: Immunodeficiency caused by external factors rather than genetic defects. - **Examples**: - **Human Immunodeficiency Virus (HIV)**: Targets CD4 T cells, leading to AIDS when untreated. - **Malnutrition**: Deficiency in essential nutrients (e.g., protein, zinc, and vitamins) impairs immune function. - **Chronic Diseases**: - Diabetes mellitus: Impairs phagocytosis and T cell responses. - Chronic kidney disease: Impairs neutrophil and lymphocyte function. - Cancer: Especially hematological malignancies like leukemia and lymphoma. - **Infections**: Certain infections like tuberculosis or measles suppress immune function. - **Investigation**: - Blood tests for CD4 T cell counts (e.g., in HIV). - Nutritional assessments (e.g., vitamin levels, protein markers). - Screening for underlying infections or chronic diseases. **3. Iatrogenic Immunodeficiency** - **Definition**: Immunodeficiency resulting from medical treatment or interventions. - **Examples**: - **Chemotherapy/Radiation Therapy**: Suppresses bone marrow, reducing white blood cell production. - **Immunosuppressive Drugs**: Used in organ transplantation or autoimmune diseases (e.g., corticosteroids, calcineurin inhibitors, and monoclonal antibodies). - **Biologic Therapies**: Anti-TNFα agents (e.g., infliximab) used in conditions like rheumatoid arthritis or Crohn's disease can increase susceptibility to infections. - **Surgical Removal of Immune Organs**: Splenectomy reduces immune function, especially against encapsulated bacteria. - **Investigation**: - Complete blood count (CBC) to assess white blood cells. - Monitoring of immune parameters (e.g., immunoglobulin levels, lymphocyte counts). - Infection surveillance during treatment. **Diagnostic and Investigative Tools:** - **Complete Blood Count (CBC)**: Assesses leukocyte levels, including neutrophils and lymphocytes. - **Immunoglobulin Testing**: Measures IgG, IgA, and IgM to detect antibody deficiencies. - **Flow Cytometry**: Identifies immune cell populations (e.g., T cells, B cells, NK cells). - **Functional Assays**: Evaluates specific immune functions, such as phagocytosis or complement activation. - **Genetic Testing**: Identifies congenital causes through mutation analysis. - **Infection Screening**: Detects common pathogens in acquired or iatrogenic immunodeficiency (e.g., HIV, TB). - **To discuss how these conditions may affect the oral tissues** **1. Congenital Immunodeficiency** - **Severe Combined Immunodeficiency (SCID)**: - **Effect on Oral Tissues**: Increased risk of opportunistic infections, including fungal infections like oral candidiasis, and viral infections like herpes simplex virus (HSV). Poor wound healing. - **X-linked Agammaglobulinemia (XLA)**: - **Effect on Oral Tissues**: Increased susceptibility to bacterial infections, leading to periodontal disease, recurrent dental abscesses, and delayed tooth eruption due to chronic infection. - **DiGeorge Syndrome**: - **Effect on Oral Tissues**: Cleft palate, enamel hypoplasia, and susceptibility to fungal and bacterial infections. - **Chronic Granulomatous Disease (CGD)**: - **Effect on Oral Tissues**: Gingivitis, periodontitis, and persistent oral ulcers due to impaired phagocytic function and recurrent bacterial or fungal infections. - **Complement Deficiencies**: - **Effect on Oral Tissues**: Increased susceptibility to periodontal pathogens, leading to aggressive periodontitis. **2. Acquired Immunodeficiency** - **HIV/AIDS**: - **Oral Manifestations**: - Oral candidiasis (pseudomembranous, erythematous, or angular cheilitis). - Oral hairy leukoplakia caused by Epstein-Barr Virus (EBV). - Kaposi's sarcoma presenting as purplish lesions on the mucosa. - Necrotizing ulcerative gingivitis/periodontitis (NUG/NUP). - Increased risk of opportunistic bacterial infections and delayed healing. - **Malnutrition**: - **Effect on Oral Tissues**: Atrophic glossitis, angular cheilitis, oral ulcerations, and delayed wound healing due to deficiencies in vitamins (e.g., B-complex, C) and proteins. - **Chronic Diseases (e.g., Diabetes)**: - **Effect on Oral Tissues**: Increased risk of periodontitis due to impaired immune responses and delayed wound healing; oral fungal infections are common. - **Cancer**: - **Effect on Oral Tissues**: Mucositis, xerostomia, and opportunistic infections due to immunosuppression from cancer itself or treatments. **3. Iatrogenic Immunodeficiency** - **Chemotherapy/Radiation Therapy**: - **Effect on Oral Tissues**: Mucositis (painful inflammation of mucous membranes), xerostomia, oral ulcerations, increased susceptibility to infections (e.g., candidiasis, herpes simplex), and delayed healing of surgical sites. - **Immunosuppressive Drugs (e.g., corticosteroids, biologics)**: - **Effect on Oral Tissues**: Predisposition to opportunistic infections (fungal, viral, and bacterial), delayed healing, and higher risk of periodontal disease. - **Splenectomy**: - **Effect on Oral Tissues**: Increased risk of oral infections by encapsulated bacteria such as *Streptococcus pneumoniae* and *Haemophilus influenzae*. **Common Oral Pathologies in Immunodeficient Patients:** 1. **Oral Candidiasis**: - Caused by fungal overgrowth, often due to weakened immunity. - Presents as white plaques, redness, or painful cracks at the corners of the mouth. 2. **Periodontal Disease**: - Aggressive gingivitis or periodontitis due to impaired immune response to bacterial biofilm. 3. **Oral Ulcerations**: - Persistent, non-healing ulcers caused by impaired immune surveillance and healing. 4. **Viral Lesions**: - Reactivation of latent herpesviruses (e.g., HSV or EBV) can cause ulcers or leukoplakia. 5. **Mucositis**: - Common in patients undergoing chemotherapy or radiation therapy; presents as painful inflammation and ulceration of the oral mucosa. **Implications for Dental Care:** 1. **Frequent Monitoring**: - Regular dental check-ups to monitor for infections, periodontal disease, or other complications. 2. **Infection Control**: - Prophylactic antifungal or antibacterial treatment in high-risk patients. 3. **Supportive Care**: - Address symptoms like xerostomia with saliva substitutes, manage mucositis with pain relief and protective coatings, and ensure proper nutrition to support healing. 4. **Collaboration**: - Close coordination with medical teams managing the underlying immunodeficiency is critical for effective dental management. - **To overview important human pathogens which are cause/consequences of immunodeficiency and relate these to oral and systemic disease states which may be encountered in dental practice** **1. Categories of Immunodeficiencies:** - **Primary Immunodeficiencies**: Congenital conditions affecting innate or adaptive immunity (e.g., Severe Combined Immunodeficiency - SCID, DiGeorge Syndrome). - **Secondary Immunodeficiencies**: Acquired conditions, often due to external factors (e.g., HIV/AIDS, chemotherapy, malnutrition). **2. Pathogens Commonly Associated with Immunodeficiency:** - **Fungal Pathogens**: - *Candida albicans*: Opportunistic oral and systemic infections (e.g., oral thrush). - *Aspergillus spp.*: Associated with invasive aspergillosis in immunocompromised patients. - **Viral Pathogens**: - *Human Herpesviruses*: HSV-1 (herpes labialis), HSV-2, Cytomegalovirus (CMV), and Epstein-Barr Virus (EBV). - *HIV*: Leads to secondary immunodeficiency and increases susceptibility to oral and systemic opportunistic infections. - **Bacterial Pathogens**: - *Mycobacterium tuberculosis*: Extrapulmonary and oral manifestations in immunosuppressed patients. - *Streptococcus pneumoniae*: Pneumonia and sinusitis with systemic implications. - **Parasitic Pathogens**: - *Toxoplasma gondii*: Severe encephalitis and systemic involvement in AIDS patients. **Oral Diseases Linked to Immunodeficiency** - **Oral Candidiasis**: Common in HIV/AIDS, presenting as pseudomembranous, erythematous, or angular cheilitis. - **Periodontal Disease**: Accelerated forms (e.g., necrotizing ulcerative periodontitis) in immunocompromised individuals. - **Viral Lesions**: - *Herpes Simplex Virus*: Recurrent intraoral and perioral ulcers. - *Epstein-Barr Virus*: Oral hairy leukoplakia on the lateral tongue. - **Oral Manifestations of Systemic Conditions**: - Kaposi's sarcoma in HIV/AIDS. - Oral ulcers in lupus erythematosus or other autoimmune conditions. **Systemic Disease States Encountered in Dental Practice** - **HIV/AIDS**: - Oral and systemic opportunistic infections. - Considerations for safe dental treatment (e.g., antiretroviral therapy, infection control). - **Diabetes Mellitus**: - Immune dysfunction leading to increased susceptibility to periodontal diseases and delayed wound healing. - **Cancer Therapy-Related Immunosuppression**: - Mucositis, xerostomia, and increased infection risk due to chemotherapy/radiotherapy. - **Transplant Patients**: - Immunosuppressive therapy increasing fungal, viral, and bacterial infections. - **Autoimmune Diseases**: - Oral lesions, secondary infections, and implications for management (e.g., Sjögren's syndrome, systemic lupus erythematosus). **Clinical Considerations in Dental Practice** - **Diagnosis**: - Recognize oral manifestations as potential indicators of systemic immunodeficiency. - **Management**: - Antifungal, antiviral, or antibacterial treatments tailored to the pathogen. - Collaboration with medical specialists for systemic conditions. - **Prevention**: - Emphasis on oral hygiene and preventive care in immunocompromised patients. - **Infection Control**: - Adherence to strict sterilization and infection control protocols. - **Patient Education**: - Discuss the importance of maintaining oral health to minimize systemic complications. - **To explain key examples of immunosuppression including causes and consequences** **Key Examples of Immunosuppression** **1. Primary Immunodeficiency** - **Cause**: Genetic or congenital defects affecting immune system components. - Example: *Severe Combined Immunodeficiency (SCID)*, where both T-cell and B-cell functions are compromised. - **Consequences**: - Increased susceptibility to recurrent infections (e.g., bacterial pneumonia, fungal infections like *Candida*). - Delayed or absent responses to vaccinations. - Risk of severe systemic infections, often life-threatening if untreated. - **Oral Implications**: - Severe oral candidiasis. - Poor healing after dental procedures. **2. Acquired (Secondary) Immunosuppression** - **Cause**: External factors that weaken the immune system. **a. HIV/AIDS** - **Cause**: Infection with the Human Immunodeficiency Virus (HIV), which targets CD4+ T cells. - **Consequences**: - Progression to AIDS leads to severe immune dysfunction. - Increased susceptibility to opportunistic infections (*Pneumocystis jirovecii*, *Toxoplasma gondii*), cancers (e.g., Kaposi\'s sarcoma). - **Oral Implications**: - Oral candidiasis, hairy leukoplakia, necrotizing ulcerative gingivitis/periodontitis. **b. Cancer Therapy (Chemotherapy/Radiotherapy)** - **Cause**: Suppression of bone marrow activity, reducing white blood cell counts. - **Consequences**: - Increased risk of bacterial and fungal infections. - Delayed wound healing, anemia, and mucositis. - **Oral Implications**: - Oral mucositis, xerostomia, and increased risk of infections like *Candida*. **c. Organ Transplantation** - **Cause**: Immunosuppressive medications (e.g., corticosteroids, calcineurin inhibitors) used to prevent graft rejection. - **Consequences**: - Increased vulnerability to viral (e.g., *Cytomegalovirus*), fungal (*Aspergillus*), and bacterial (*Listeria monocytogenes*) infections. - **Oral Implications**: - Reactivation of herpesviruses. - Increased susceptibility to periodontal disease and oral fungal infections. **d. Diabetes Mellitus** - **Cause**: Poorly controlled blood sugar impairs neutrophil function and vascular integrity. - **Consequences**: - Recurrent bacterial infections (e.g., skin and urinary tract infections). - Increased risk of severe periodontal disease. - **Oral Implications**: - Delayed healing after extractions. - Increased risk of oral candidiasis and xerostomia. **3. Drug-Induced Immunosuppression** - **Cause**: Use of medications that intentionally or unintentionally suppress the immune system. - **Corticosteroids**: Reduce inflammation by suppressing immune responses. - **Biologic Drugs**: E.g., TNF-α inhibitors used for autoimmune diseases (e.g., rheumatoid arthritis, Crohn\'s disease). - **Consequences**: - Increased risk of infections like *Mycobacterium tuberculosis* and reactivation of latent viruses (*Varicella-zoster virus*). - **Oral Implications**: - Reactivation of herpes simplex virus. - Increased oral fungal infections. **Consequences of Immunosuppression** - **Infectious Diseases**: - Opportunistic infections (*Candida*, *Aspergillus*, *Pneumocystis jirovecii*). - Recurrent or chronic infections. - **Cancer Susceptibility**: - Immunosurveillance failure increases the risk of malignancies like lymphoma, Kaposi\'s sarcoma. - **Delayed Healing**: - Impaired tissue repair after surgeries or injuries. - **Systemic Complications**: - Sepsis from untreated infections. - Multisystem organ involvement in severe infections.