Hospital Dentistry Exam 4

- Cancer, HSCT, GVHD, Langerhans Cell Histiocytosis; Sickle Cell Disease + Thalassemias, Neutropenias, Crohn's Disease and Celiac Disease

leukemias and CNS tumors

what are the most common types of cancer affecting children 0-14

CNS, lymphoma, Leukemia, thyroid carcinoma, germ cell and gonadal tumors

what are the most common cancers affecting adolescents 15-19?

• paleness, loss of energy

• sudden tendency to bruise and/or bleeding

• persistent bone pain/limping

• unexplained fever/illness

• sudden eye/vision change

• frequent headaches, often with vomiting

• sudden weight loss

• lymphadenopathy

• testicular mass

• ongoing pain

• abdominal mass

• gingival enlargement

what are some of the signs of cancer

chloroma

soft tissue mass of leukemic cells. rapidly growing, firm, nodular mass. capable of local tissue destruction. occurs in children <15 years. occurs in 10% of AML cases

chemotherapy

interferes with DNA synthesis and function and targets actively proliferating cells

radiotherapy

causes damage to DNA which disrupts the replication process. targets regularly dividing cells. any cell in the path may be affected. very high dose will affect non-proliferating cells

nausea, vomiting, alopecia, mucositis, cutaneous erythema, sialadenitis, fatigue, anorexia, lymphopenia, diarrhea

what are some of the acute effects of cancer therapy?

growth and development, reproductive system, craniofacial growth, osteoporosis, secondary malignancies, possible damage to heart, lungs, kidney, CNS

what are the long-term effects of cancer and cancer therapy

brain and spinal cord tumors

what are the most common solid tumors in children

neuroblastoma

starts in early forms of nerve cells found in the embryo of fetus from the sympathetic nervous system. develops in infants and young children, rare >10 years of age. can happen anywhere but usually occurs in the abdomen. 1/3 are in the adrenal glands

nephroblastoma (Wilms tumors)

tumor in the kidney. 5% prevalence. rarely occurs in both. most often in 3-4 year old children. starts as asymptomatic swelling or lump in abdomen

rhabdomyosarcoma

most common type of soft tissue sarcoma. tumor of skeletal muscles. occurs anywhere in the body. often presents with pain/swelling at the mass site

retinoblastoma

tumor of the eyes. occurs around 2 years of age, rarely occurs after 6 years of age

osteosarcoma

bone cancer. occurs in area where bone is growing quickly. usually affects in teen years. symptoms: bone pain, swelling

Ewing sarcoma

occurs in young teens. bone cancer usually occurring in pelvic bones, chest wall, legs

lymphomas

cancer o the immune system affecting lymph nodes, tonsils, thymus

Hodgkin lymphoma

3%, usually affects people in their 20s, rare in children under 5

non-Hodgkin lymphoma

5%, usually affects younger patients (younger than 20s) but rare <3 years. grows quickly

leukemia

most common childhood cancer. 28% of cases. highest incidence 1-4 years. characterized by clonal proliferation and dysfunction of blood cells. overall rates substantially higher for white children

acute myeloid leukemia (AML)

affects bone marrow cells that differentiate into red blood cells, platelets, and other types of WBC. immature cells accumulate and rapidly replace bone marrow leading to decreased production of regular cells. incidence increases with age. unknown etiology, may be ionizing radiation, genetics, chemical/drug exposure. Can only be treated with chemotherapy. for first part, remission induction, you want to reduce the number of leukemic cells below clinical detection. For consolidation you completely eradicate leukemic cells. then patients need hematopoietic stem cell transplant

remission

first part of treatment for leukemia. reduces number of leukemic cells below clinical detection. <5% of blasts in bone marrow, no leukemic cells in peripheral blood. normal peripheral blood counts, no extramedullary involvement. achieved with chemotherapy

consolidation

second phase of leukemia treatment. completely eradicates leukemic cells

acute lymphoblastic leukemia (ALL)

most common childhood leukemia (21% of all cases). peak incidence 2-6 years old. affects bone marrow cells that differentiate into lymphocytes (B and T cells). heterogenous disease —> tx done according to phenotype, genotype, and risk. prognosis worst if <1 year and best for ages 1-9. high risk for children 10 and older. If WBC >200,000 at diagnosis, bad prognosis. Best if WBC <50,000 at time of diagnosis

lymphadenopathy, sore throat, laryngeal pain, gingival bleeding, oral ulcerations

what are some of the oral manifestations of ALL?

remission induction, consolidation, delayed intensification or reconsolidation, maintenance

what are the 4 steps of ALL treatment?

7-10 days

extractions should be done at least this amount of time before cancer therapy starts to allow adequate healing

nystatin

anti fungal but not effective to prevent or treat oral infection in immunocompromised patients

mandible

which part of the jaw is more radiosensitive? if TBI is done before 6 years there will be reduced growth of the alveolar processes and severe disturbances in dental development

Langerhans Cell

immature dendritic cells which lack the ability to be functional antigen presenting cells and lack dendritic processes

Langerhans Cell Histiocytosis

disease characterized by uncontrolled histiocytic proliferation in multiple organs that triggers an immunologically mediated inflammatory response. unknown etiology. can occur in skeleton, skin, or pituitary gland. can be self-limiting to rapidly progressive. rare, more likely to affect people <15 and peak incidence is 1-3 years. affects boys more often but this reverses in adulthood. can be unifocal (single organ) or affect multiple organs (multifocal).

unifocal Langerhans cell histiocytosis

usually benign form of LCH. affects older adults and children. usually found in skull or vertebrae

multifocal langerhans cell Histiocytosis

aggressive version of LCH. usually seen in infants. multiple bone lesions with adjacent soft tissue involvement. if seen in liver, lungs, bone marrow, and spleen high risk. low risk: skin, bone, lymph nodes, pituitary gland

seborrheic dermatitis, red poplar rash (groin, abdomen, back, and chest)

skin presentation for LCH (usually 1st presentation of disease)

lytic lesions, often surrounded by soft tissue mass (can be asymptomatic/painful)

what is the presentation of bone lesions for LCH? most common presentation in children

Birbeck granule positive cells

rod-shaped or "tennis racket" cytoplasmic organelles found exclusively in Langerhans cells, a type of dendritic cell. definitive diagnosis for LCH made with presence of these

diabetes (posterior pituitary gland infiltration), growth hormone deficiency (anterior pituitary gland infiltration), orthopedic problems, hearing problems, biliary cirrhosis, cerebella ataxia, cognitive dysfunction, pulmonary fibrosis, other malignancies

what are the long-term consequences of LCH?

mandible, posterior

which area of the jaws is most likely to be affected for LCH?

intraoral mass, pain, gingivitis, loose teeth, ulcer, impaired healing, halitosis, jaw fracture, gingival recession, periodontal pockets

what are some of the oral cavity signs and symptoms of LCH?

9-12 months

patient should not receive dental treatment for this amount of time after HSCT, especially if patient has GVHD

chronic GVHD

results form an immune response mediated via donor lymphocytes (the graft) that recognizes antigens expressed in non-malignant tissues of the patient (host) due to disparities in HLAs between the donor and recipient. although the patients and donors are matched as closely as possible, some minor antigens can go undetected. characterized by chronic inflammation, collagen deposition and fibrosis affecting the skin, liver, GI tract, oral cavity, genitals, nervous and musculoskeletal systems and eyes. can lead to organ dysfunction as well

thick, tight, fragile with poor wound healing capacity, hypo/hyper pigmentation, destruction of sweat glands (increased hyperthermia)

what are the signs of GVHD for skin?

hair loss, premature graying of hair, eyelashes and eyebrows, thin, brittle hair

what are the signs of GVHD for hair?

nail loss, vertical ridging, and fragile nails

what are some of the signs of GVHD for nails?

sicca syndrome, photophobia, pain

what are the signs of GVHD for the eyes?

cirrhosis, liver failure

what are the signs of GVHD for the liver?

obstructive lung disease, wheezing

what are some of the signs of GVHD for the lungs

nausea, vomiting, diarrhea, malabsorption

what are the signs of GVHD for the GI tract

contractures, myalgias, arthritis

what are the signs of GVHD for the musculoskeletal system

infection, progressive organ failure

what are the major causes of death in patients with GVHD

glucocorticoids

what is the usual treatment for patients with GVHD

lichen planus, Sjogrens, scleroderma

clinically GVHD oral lesions can resemble lesions form these diseases

atrophy, erythema, lichenoid lesions and/or hyperkeratotic changes, large non-healing ulcers, desquamative gingivitis, pseudomonas, reduced salivary flow, growths, pyogenic granulomas, atrophic glossitis, palatal mucoceles, soft tissue fibrosis, limited tongue mobility, decreased opening

what are some of the oral manifestations of GVHD?

2 weeks

if a patient has fever, malaise, and bleeding form the gums when should those symptoms generally resolve for healthy patients

hemoglobin

oxygen-carrying protein in RBCs

hematocrit

amount of RBCs in the blood

red blood cells, platelets, granulocytes (eosinophils, neutrophils, basophils)

which blood cells come from the myeloid lineage

plasma cells, b-cells, t-cells, natural killer cells

which blood cells are derived from the lymphoid lineage

12-18 g/dL

normal lab value for hemoglobin

32-52%

normal hematocrit value

dehydration

what can lead to low hematocrit? (when patient is sick ex)

autoimmune disorder, bone marrow disorder, cancer, medication induced

what are some of the things that can cause leukopenia?

infection, inflammation, medication, exercise, immune disorder

what are some of the things that can cause leukocytosis?

% neutrophils * total white cell count

how do you calculate absolute neutrophil count? (ANC)

<1000/mm3

at this ANC, patient is at increased risk for infection so elective dental treatment should be deferred. moderate neutropenia

<500/mm3

SEVERE neutropenia. at this ANC, patients need to be supplemented with antibiotic

bacterial infections, hemorrhage, diabetic acidosis

when will you see high neutrophil counts?

viral and bacterial infections, acute and chronic lymphocytic leukemia, antigen reaction

when will you see high lymphocyte count?

parasitic and allergic conditions, blood dyscrasias, pernicious anemia

when will you see increased eosinophil count?

blood dyscrasia

when will you see an increase in basophil count?

Hodgkin’s disease, lipid storage disease, recovery from severe infections, monocytic leukemia

when will you see an increase in macrophage/monocyte count?

persistent or high fever, spreading localized infection, recurrent soft or connective tissue infection, suspicion of chronic inflammatory disease, immunodeficiency, or malignancy

when should you order a CBC for patients?

diapedesis

antigen presenting cells release cytokines that attract other immune cells. rolling neutrophils bind to endothelial glycoproteins. extravasation of blood cells (and neutrophils) through capillary walls

chronic infection, cancers, immunosuppression, medication-induced, nutritional, sequestration (hypersplenism)

causes of acquired neutropenia

autoimmune disorders, cyclic neutropenia

congenital causes of neutropenia

chemotherapy drugs, antibiotics (sulfonamides, penicillins, cephalosporins), anticonvulsants (carbamazepine, phenytoin), antipsychotics (clozapine), antidepressants (imipramine, amitriptyline), immunosuppressants (methotrexate, cyclophosphamide, azathioprine), antithyroid medications (methimazole, propylthiouracil), NSAIDs

medications that can cause neutropenia

aphthous-like ulcers, gingival inflammation and attachment loss, mucositis, delayed wound healing, early loss of primary and permanent teeth, abscesses and soft tissue infections, halitosis

what are some of the oral clinical manifestations of neutropenia?

cyclic neutropenia

autosomal dominant condition. affects monocytes, platelets, lymphocytes, and reticulocytes. signs: fever, malaise, sore throat, stomatitis, lymphadenopathy, severe gingivitis with ulceration

leukocyte adhesion defect (LAD)

caused by surface glycoprotein defect. leads to severe generalized periodontitis in primary and permanent teeth refractory to treatment. will lose teeth early - will need dentures, not implant candidates. get frequent soft tissue infections. treatment: stem cell transplant. better oral hygiene will slow process - need regular scaling, CHX, iodine

Papillon-Lefevre Syndrome

palmar plantar keratosis, attachment loss leading to early loss of primary and permanent teeth, severe gingival inflammation, need OHI, antibiotics, and extraction if needed. caused by Cathespin C defect . radiographically see “floating teeth”

Cathepsin C

lysosomal cysteine protease involved in various cellular processes, particularly within the immune system. It plays a key role in activating other proteases, especially serine proteases within neutrophils and other immune cells, which are crucial for immune defense and the inflammatory response. defect linked to Papillon-Lefevre Syndrome

Chediak-Higashi

autosomal recessive disease. can be mild or typical (severe). if very severe, may require BMT. mutation in lysosome trafficking

hypophosphatasia

cause by high serum alkaline phosphatase. can usually catch from presentation of primary teeth and then treat. leads to “rootless” teeth

Kostmann syndrome

chronic severe neutropenia present at birth. leads to recurrent infections. 10-20% of cases become cancer (AML or myelodysplasia). treat with G-colony stimulating factor (a natural protein (a type of cytokine) that stimulates the bone marrow to produce more white blood cells, specifically granulocytes (a type of neutrophil))

duodenum

responsible for release of bile and pancreatic enzymes

jejunum

responsible for primary absorption of nutrients (large surface area due to villi and microvilli). in certain conditions (w/ scarring) will flatten and not be able to absorb as much

ilium

absorbs bile acids, vitamin B12, and other nutrients

cecum (and colon)

responsible for absorbing water and electrolytes

rectum (anus)

stores and controls release of stool

ulcerative colitis

limited to the large intestine/colon/rectum. inflamed areas are continuous with no patchiness. typically get pain in lower left abdomen. ulcers penetrate the inner lining of the abdomen early - bleed easily. get significant blood loss in stool

Crohn’s disease

can occur anywhere in the GI tract. get patches of inflammation in large section of the bowel. typically get more pain and in lower right abdomen. ulcers penetrate entire thickness of the abdominal lining - will need portions to be resected. stool will be darker color because bleeding occurs earlier

inner lining and distal portion of large intestine

what part of the digestive system is usually affected by ulcerative colitis?

15-30

what is the typical age for developing ulcerative colitis

diarrhea and bloody stool, abdominal cramps/pain, anemia, increased risk for colon cancer

what are some of the symptoms/concerns for ulcerative colitis?

NSAIDs

medication that should be avoided for patients with ulcerative colitis

localized corticosteroids

what medication is used most commonly for ulcerative colitis?

cyclosporine, tacrolimus, methotrexate, mercaptopurine

immunomodulators that can be used to treat ulcerative colitis

immune response, microbiome, genetics, environmental factors

what are some of the potential causes of the development of ulcers in ulcerative colitis?

humira

biological modulator. monoclonal antibodies that can be used to treat ulcerative colitis. TNF blocker

atrophic glossitis (geographic tongue), mucosal inflammation, gingivitis and periodontitis, oral thrush (oral candidiasis), angular cheilitis, oral lesions (granulomatous lesions, pyostomatitis vegetans, cobblestone appearance), enamel defects

what are some of the oral manifestations of ulcerative colitis?

skip lesions

what is the pattern of lesions in Crohn’s disease