Pathology Final SG

Cellular response to stress and noxious stimuli

Types of necrosis

• Coagulative necrosis:

  • Architecture of dead tissues is preserved for a span at least of some days; affected tissue exhibits a firm texture; the injury denatures not only the structural proteins but also enzymes and so blocks the proteolysis of dead cells; necrotic cells are ultimately removed by phagocytosis by infiltrating leukocytes and digestion of the dead cells by the enzymes of leukocytes; Ischemia caused by obstruction in a vessel may lead to coagulative necrosis of the suppled tissue in all organs except for the brain. A localized area of coagulative necrosis is called an infarct

• Liquefactive necrosis:

  • Digestion of dead cells resulting in transformation of the tissues into a liquid viscous mass. It is seen in focal bacterial or, occasionally, fungal infections, because microbes stimulate the accumulation of leukocytes and the liberation if enzymes from these cells. The necrotic material is frequently creamy yellow because of the presence of dead leukocytes and is called pus

• Gangrenous necrosis:

  • A term usually applied to a limb, generally lower leg, that has lost its blood supply and has undergone necrosis (usually coagulative necrosis) involving multiple tissue planes. When bacterial infection is superimposed there is more liquefactive necrosis because of the actions of degradative enzymes in the bacteria and the attracted leukocytes (giving rise to the term wet gangrene)

• Caseous necrosis:

  • Is encountered most often in foci of tuberculous necrosis. The term caseous (cheese-like) is derived from the febrile white appearance of the area of necrosis.

• Fat necrosis:

  • It refers to focal area of fat destruction, typically resulting from release activated pancreatic lipases into the substance of the pancreas and peritoneal cavity This occurs in calamitous abdominal emergency known as acute pancreatitis

• Fibrinoid necrosis:

  • a special form of necrosis usually seen in immune reactions involving blood vessels. This typically occurs when complexes of antigens and antibodies are deposited in the wall of the arteries. Deposits of these ‘immune complexes’ together with fibrin that has leaked out of vessels, result in a bright pink and amorphous appearance under the microscope

Morphogenic alterations in cell injury

• REVERSIBLE INJURY

  • 2 features recognized under light microscope:

    • Cellular swelling

    • Fatty changes

  • Cellular swelling appears whenever cells are unable to maintain ionic and fluid homeostasis and is a result of failure of energy-dependent ionic pumps in the plasma membrane

  • Fatty changes occur in hypoxic injury and various forms of toxic or metabolic injuries

• IRREVERSIBLE INJURY: NECROSIS

  • Morphologic appearance is the result of:

    • Denaturation of intracellular proteins

    • Enzymatic digestion of the lethally injured cells

  • Cells unable to maintain membrane integrity and contents leak out Elicit inflammation in surrounding tissues

• Necrosis

  • The morphologic appearance of necrosis as well as necroptosis is a result of denaturation of intracellular proteins and enzymatic digestion of the lethally injured cells

  • The enzymes that digest the necrotic cells are derived from lysosomes of the dying cells themselves

  • NUCLEAR CHANGES

    • Appears due to nonspecific breakdown of DNA

      • Pyknosis: characterized by nuclear shrinkage and increased basophilia; the chromatin condenses into solid , shrunken basophilic mass

      • Karyorrhexis: pyknotic nucleus undergoes fragmentation

      • Karyolysis: the basophilia of chromatin may fade, a change that presumably reflects loss of DNA because of enzymatic degradation by endo nucleases

Pathologic Calcifications

• Dystrophic calcification: Deposition of calcium at sites of cell injury and necrosis

  • dead or dying tissues its called this

• Metastatic calcifications: Deposition of calcium in normal tissues, caused by hypercalcemia (usually a consequence of parathyroid hormone excess)

  • in normal, vital tissues

Acute and Chronic Inflammation

• Acute Inflammation: the initial rapid response to infections and tissue damage

  • Develops within minutes to hours and is of short duration, lasting for several hours or a few days

  • Main characteristics include exudation of fluids and plasma proteins (edema) and emigration of leukocytes, predominantly neutrophils

  • When desired goals are achieved, the reaction subsides; if response fails, the reaction progresses to chronic phase

  • Host defense seen in innate immunity

  • Three major components:

    • 1. Dilatation of small blood vessels leading to an increase in blood flow

    • 2. Increased permeability of microvasculature enabling plasma proteins and leukocytes to leave the circulation

    • 3. Emigration of leukocytes from microcirculation, their accumulation in the focus of

      injury, and their activation to eliminate the offending agent

  • Five classic signs of acute inflammation

    • Rubor: rednes

    • Tumor: swelling

    • Calor: warmth

    • Dolor: pain

    • Functio laesa: loss of

      function

• CHRONIC INFLAMMATION

  • Is of longer duration

  • Associated:

    • More tissue destruction

    • Presence of lymphocytes and macrophages

    • Proliferation of blood vessels

    • Deposition of connective tissue

    • This reaction seen in adaptive immunity

Causes of Edema and effusion

Hemostasis and thrombosis

Role of Coagulation in hemostasis

Marfan Syndrome (Ch 6. 43-50)

• Disorder of connective tissue

  • manifested principally by changes in the skeletal, eyes, and cardiovascular system

• 1 in 5000 people

• 70-80% of cases are familial and transmitted by AD inheritance

  • remainder are sporadic and arise from new mutations

• Caused by mutation in the FBN1 gene encoding fibrillin, which is required for structural integrity of connective tissues

• clinical features:

  • tall stature

  • long fingers

  • bilateral subluxation of lens

  • mitral valve prolapse

  • aortic aneurysm

  • aortic dissection

• Oral features

  • lips marked incompetent

  • retrognathia

  • a narrow, highly arched palate with crowding of the teeth

  • significantly greater risk for dental caries, higher pulpal calcifications and gingival inflammation, and TMJ subluxation

Ehlers-Danlos Syndrome (Ch 6. 52-58)

• Comprise a clinically and genetically heterogenous group of disorders that result from some mutations in the genes that encode collagen, enzymes that modify collagen, and less commonly other proteins present in the extracellular matrix

• Several variants of EDS, all characterized by defects in collagen synthesis or assembly

• Each of the variants is caused by a distinct mutation involving one of the several collagen genes or genes that encode other ECM protein

• Clinical features:

  • fragile hyperextensible skin vulnerable to trauma

  • hypermobile joints

  • ruptures involving the colon, cornea and large arteries

• Wound healing is poor

• Oral Manifestations

  • marked periodontal disease; seen at a relatively early age

  • easy bruising and bleeding during minor manipulations of the oral mucosa

  • recurrent subluxation of the TMJ

  • most patients have normal teeth

  • Ability of 50% of patients to touch the tip of their nose with their tongue (Gorlin sign)

    • seen in less than 10% of general population

• Treatment:

  • accurate diagnosis and genetic counselling is very important

Familial Hypercholesterolemia (FHCL) (Ch 6. 60-66)

• Caused by mutations in genes encoding the:

  • LDL (85%)

  • ApoB protein (5-10%)

  • activating mutations of PCSK9 (1-2%)

• It affects how the body regulates and removes cholesterol

• Autosomal Dominant disorder

• Patients develop hypercholesterolemia because of impaired transportation of LDL into the cells

• In heterozygotes for mutations in the LDL gene, elevated serum cholesterol greatly increases the risk of atherosclerosis and resultant coronary artery disease

• homozygotes have an even greater increase in serum cholesterol and a higher frequency of ischemic heart disease

  • cholesterol also deposits along tendon sheaths to produce xanthomas (fatty deposits that build up under the skin)

• Clinical Features

  • Tendinous xanthomas

  • Corneal arcus (deposit of cholesterol in arc around cornea of eye)

  • coronary artery disease

  • the aortic root is prone to develop atherosclerotic plaque at an early age

• Treatment

  • Heterozygous FHCL: usually treated by statin therapy

  • Homozygous FHCL is harder to treat:

    • high dose of statin

    • LDL cholesterol apheresis (therapy that removes LDL from patient blood)

    • gene therapy

McArdle and Von Gierke disease (Ch 6. 80-82)

• Glycogen storage diseases (glycogenosis)

  • inherited deficiency of enzyme involved in glycogen metabolism can result in storage of normal or abnormal forms of glycogen, predominantly in liver or muscles, but also in other tissues as well

• Autosomal recessive

• Von Gierke Disease

  • most common hepatic form

  • liver cells store glycogen

    • because of lack of hepatic glucose-6-phosphatase; enlarged liver and patients have hypoglycemia

• McArdle Disease

  • myopathic form

  • lack of muscle phosphorylase giving rise to storage in skeletal muscles and cramps after exercise

Down Syndrome (Ch 6. 84-88)

• Associated with an extra copy of genes on chromosome 21, most commonly due to trisomy 21 and less frequently from translocation of extra chromosomal material from chromosome 21 to other chromosomes

• Maternal age has strong influence on the incidence of trisomy 21

• Patients have severe intellectual disability, flat facial profile, epicanthic fold, cardiac malformations, higher rise of leukemia, infections, and premature development of Alzheimer disease

• oral manifestations

  • open mouth with tendency of tongue protrusion

    • fissured and furrowed tongue

  • Mouth breathing with drooling

    • chapped lower lip and angular cheilitis

  • increased periodontal disease

Klinefelter Syndrome (Ch 6. 97-99)

• HAPPENS IN MEN

• is a sex chromosome disorder in boys and men that result from the presence of an extra X chromosome in cells (46XXY)

  • at least 2 X and one or more Y chromosomes

• Patients have testicular atrophy, sterility, reduced body hair, gynecomastia (enlargement of breast tissue in males) and eunuchoid body habitus (body shape characterized by long limbs, reduced muscle mass, narrow shoulders, and a wider-than-usual pelvis)

• most common cause of male sterility

Turner Syndrome (Ch 6. 100-102)

• HAPPENS IN FEMALES

• Monosomy X chromosomal abnormality occurs as a random event during the formation of reproductive cells (eggs and sperm) in the affected person’s parent; most cases not inherited

• chromosomal affects development in females

• short stature, webbing of the neck, cardiovascular malformations, amenorrhea, lack of secondary sex characteristic, and fibrotic covaries (lack of estrogen)

• Most common is short stature, which becomes evident by about age 5

Systemic Lupus Erythematosus (Ch 4. 125-136)

• Most common connective tissue diseases in the US

• Type III hypersensitivity

• Serious multisystem disease

• exhibits a variety of cutaneous and oral manifestations

• very difficult to diagnose in early stages of the disease (nonspecific and vague pattern)

• Women affected 8-10x more frequently than males

  • average age is 31 years

• Clinical features

  • common findings include fever, weight loss, arthritis, fatigue, and general malaise

  • in 40-50% of patients, a characteristic butterfly rash (Malar rash) is seen (over the molar area and nose, typically sparing the nasolabial folds)

  • sunlight makes the lesions worse

  • Arthritis- multiple joints (polyarthritis)\

  • photosensitivity

  • Kidneys are affected 40-50% of patients; may ultimately lead to kidney failure, thus it is typically the most significant aspect of the disease

  • Cardiac involvement is common; pericarditis is the most frequent involvement

    • at autopsy nearly 50% of patients display warty vegetation affecting the heart valves (Libman-Sacks endocarditis)

    • some patients may develop superimposed bacterial endocarditis

• Oral lesions

  • Develop in 5-25% of patients

  • Usually affect palate, buccal mucosa, and gingiva

  • may be lichenoid or granular or nonspecific

  • Lupus cheilitis: involvement of the vermillion border of the lower lip is sometimes seen

  • Varying degree of ulcerations, pain, erythema, and hyperkeratosis may be seen

HIV/ AIDs (Ch 4. 208-224)

• Secondary immunodeficiencies

  • encountered in individuals with cancer, diabetes, and other metabolic diseases, malnutrition, chronic infections, and in persons receiving chemotherapy or radiation therapy for cancer or immunosuppressive drugs to prevent GVHD or to treat autoimmune disease

• HIV infection/AIDS

  • a virus that attacks the body’s immune system; if HIV is not treated it can lead to AIDS (acquired immunodeficiency syndrome)

  • AIDS is the late stage of HIV infection that occurs when the body’s immune system is badly damaged because of the virus

    • A person with HIV is considered to have progressed to AIDS when:

      • the # of their CD4 cells fall below 200 cells per cubic millimeter of blood (220 cells/mm³ ); in someone with a healthy immune system, CD4 counts are between 500 and 1,600 cells/mm³ )

      • OR

      • they develop one or more opportunistic infections regardless of their CD4 count

• Caused by the retrovirus human immunodeficiency virus (HIV) and is characterized by profound immunosuppression that leads to opportunistic infections, secondary neoplasms, and neurological manifestations

• In the USA, it is the:

  • 2nd leading cause of death in men between 25 and 44 years of age

  • 3rd leading cause of death in women between 25 and 44 years of age

• Retrovirus

  • after infecting a cell, a retrovirus uses an enzyme called reverse transcriptase to convert its RNA into DNA

  • the retrovirus then integrates its viral DNA into the DNA of the host cell, which allows the retrovirus to replicate

  • HIV, the virus that causes AIDS is a retrovirus

• HIV epidemiology

  • 5 group of adults at high risk for developing AIDS:

    • men who have sex with men

    • heterosexual transmission, chiefly due to contact with members of other high risk groups contacts of members of another high-risk group

    • IV drug users

    • Hemophiliacs, especially those who received large amounts of factor VIII or factor IX concentrates before 1985

    • Recipients of blood and blood components infected with HIV

  • HIV infection of the newborn

• 3 major routes of transmission

  • sexual contact

  • parental inoculation

  • passage of the virus from infected mother to their newborn

• The propertied of HIV

  • a human retrovirus belonging to the lentivirus family

  • 2 genetically different but related forms of HIV have been isolated from patients with AIDS

    • HIV-1: most common in USA, Europe and central Africa

      • Spherical shape, electron dense core containing RNA, surrounded by lipid envelope

    • HIV-2: principally in west Africa and India

• Pathogenesis and course of HIV infection and AIDS

  • virus entry into cells: requires CD 4 and coreceptors; main cellular targets are CD4+ helper cells, macrophages and dendritic cells

  • Viral replication: the virus genome integrates into host cell DNA

• Mechanism of immune deficiency:

  • Loss of CD4+ T cells; CD4 falls below 200 Cells per cubic mm of blood

    • relentless and profound depletion of CD4+ T cells (1-2 billion CD4+ cells die each day)

    • Normal CD4/CD8 ratio is 2:1 (AIDs CD4/CD8 ratio is <0.5

  • Defective macrophage and dendritic cell functions

  • Destruction of architecture of lymphoid tissue (late)

• B-Cell system in HIV infection

  • patients with AIDS are unable to mount an antibody response to a new antigen

• Progression of infection

  • Acute infection of mucosal T cells and dendritic cells

  • Viremia and dissemination of virus

  • Latent infection of cells in lymphoid tissue

  • Continuing viral replication and progressive loss of CD4+ T cells

• Clinical manifestations

  • Opportunistic infections

  • tumors (B cell lymphoma)

  • CNS abnormalities

Primary Immunodeficiency Diseases (Ch 4. 197-205)

• Caused by genetic (inherited) defects that affect the innate immunity (phagocytes, NK cells or complement) or acquired immunity (B and T cells)

• most of these are detected in infancy, between 6 months- 2 years of life

• X-Linked Agammaglobulinemia (Bruton Agammaglobulinemia)

  • characterized by failure of B cell precursors to develop into mature B cells

  • X-linked inheritance

  • Almost seen entirely in males; symptomatic; apparent at about 6 months of age as maternal immunoglobins are depleted

  • light chains are not synthesized, therefore complete immunoglobulins are absent

  • Recurrent bacterial infections

    • H. influenzae, S. pneumoniae, S. aureus

• Isolated IGA Deficiency

  • Common immunodeficiencies caused by impaired differentiation of naïve B cell to IgA-producing plasma cells

  • Patients have an extremely low levels of both serum and secretory IgA; most are asymptomatic

    • 1 in 600

  • Because IgA is the major antibody in mucosal secretions, mucosal defenses are weakened and infections occur in the respiratory, GI, and urogenital tracts

  • Symptomatic patients present with recurrent sinopulmonary infections and diarrhea

• Thymic Hypoplasia (Digeorge syndrome)

  • T-cell deficiency that results from failure of development of the thymus

  • low number of T cells in the blood and lymphoid tissue and poor defense against certain viral and fungal infections

  • 90% cases cause by a small germline deletion that maps to chromosome 22q11

    • part of the CATCH 22 syndrome

      • cardiac defects, abnormal facial features, thymic hypoplasia, cleft palate, hypocalcemia

Systemic Sclerosis (Scleroderma) (Ch 4. 172-193)

• Characterized by:

  • Chronic inflammation thought to be result of autoimmunity

  • Widespread damage to small blood vessels

  • progressive interstitial and perivascular fibrosis in the skin and multiple organs

    • The skin is most affected, but the GI tract, kidneys, heart, muscles, and lungs also are frequently involved

• Pathogenesis

  • cause is unknown

  • Disease likely results from 3 interrelated processes- autoimmune responses, vascular damage, and collagen deposition

  • Autoimmunity: CD4+ cells respond to an unknown antigen, accumulate in skin and release cytokines that activate inflammatory cells and fibroblasts; several of these cytokines stimulate transcription of genes encoding collagen and other extracellular matrix proteins

  • Vascular damage

    • microvasculature disease is present in the early course of the disease; this could be the result of chronic inflammation; eventually widespread narrowing of the microvasculature leads to ischemic injury and scarring

  • Fibrosis:

    • fibroblasts of these patients have a intrinsic abnormality that causes them to produce excessive amount of collagen

• Clinical Features:

  • Women are 3-5x more frequently affected than men

  • 50-60 year age group

  • although SS shares many features with SLE, RA, and polymyositis, its distinctive features are the striking skin changes

  • insidious onset, with the cutaneous changes often responsible for bringing the problem to the patients attention

  • Raynaud phenomenon

    • manifested as numbness and tingling of fingers and toes caused by episodic vasoconstriction of arteries and arterioles, is seen in virtually all patients

    • often first sign of the disease

    • vasoconstrictive event triggered by emotional distress or exposure to cold

    • not specific to SS; can also be seen in healthy individuals and other autoimmune diseases

  • Dysphagia

    • attributed to esophageal fibrosis and its resultant hypomobility is present in more than 50% of patients; eventually destruction of the esophageal wall leads to atony and dilation, especially at its lower end

  • Respiratory difficulty

    • caused by pulmonary fibrosis may result in right-sided cardiac dysfunction

  • Myocardial fibrosis

    • may cause cardiac failure

  • Skin

    • develops a diffuse and hard texture, and its surface is usually smooth

  • Facial skin

    • subcutaneous collagen depositions results in characteristic smooth, taut, masklike facies; nasal alae become atrophied

  • Hands

    • fingers may be fixed in a claw-like position with resorption of terminal phalanges (acro osteolysis)

  • Internal organ fibrosis and/or vascular damage

• Oral features:

  • occur in varying degrees

  • Microstomia

    • develops as a result of deposition of collagen in perioral tissues

      • seen in 70% of patients and results in limited mouth opening

  • Characteristic furrows radiating from the mouth produce a “purse string” appearance

  • loss of attached gingival mucosa and multiple areas of gingival recession may occur

• Dental radiographs

  • diffuse widening of the periodontal ligament space is often present throughout the dentition

    • extent of widening may vary

  • Varying degrees of resorption of the posterior ramus of the mandible, the coronoid process, the chin, and the condyle may be detected on panoramic radiographs (seen in 10-20% if patients

• Limited cutaneous systemic sclerosis

  • was preciously referred to as CREST syndrome to denote key features

    • C-calcinosis

    • R-Raynaud phenomenon

    • E-esophageal dysmotility

    • S-sclerodactyly

    • T-telangiectasias

• Laboratory studies

  • virtually all patients have that react to a variety of nuclear antigens (ANAs)

  • two ANA strongly associate with sytemic sclerosis have been established

  • one of these directed against DNA topoisomerase I (anti-scl 70), is highly specific, it is present 10%-20% of patients with diffuse systemic sclerosis

  • The other, anticentromere antibody is found in 20-30% of patients, who tend to have CREST Syndrome

• Treatment

  • difficult; natural waxing and waning course of the disease makes it difficult to assess the effectiveness of a given treatment in an open trial

  • Systemic medications such as penicillamine, are prescribed to inhibit collagen production

  • other management strategies are directed at controlling symptoms

  • dental symptoms: collapsible dentures

Sjogren Syndrome (Ch 4. 160-171)

• Chronic disease characterized by dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) resulting from immunologically mediated destruction of the lacrimal and salivary glands

• occurs as an isolated disorder (primary form) also known as sicca syndrome or more often in association with another autoimmune disease (secondary form)

• among the associated disorders, rheumatoid arthritis is the most common, but some patients may have SLE, Scleroderma, vasculitis, or thyroiditis

• Pathogenesis

  • the characteristic decrease in tears and saliva (sicca syndrome) is the result of lymphocytic infiltration and fibrosis of the lacrimal and salivary glans

  • the infiltrate contain activated CD4+ helper T-cells and some B cells, including plasma cells

  • initiating trigger may be a viral infection of the salivary glands, which causes local cell death and release of tissue self-antigens

  • 75% of patients have rheumatoid factor whether co-existing RA is present or not

  • decreased saliva and tears result from inflammatory destruction of exocrine glands

  • Lymphatic infiltration (predominantly CD4+ T cells and some plasma cells) and fibrosis of lacrimal and salivary glands

• Clinical Features:

  • mostly commonly occurs in women between 50-60 years of age; rare examples have been described in children

  • female ration is 9:1

  • keratoconjunctivitis produces blurring of vision, burning and itching, and thick secretions

  • Xerostomia results in difficulty in swallowing solid food, a decrease in the ability to tast, cracks and fissures in the tongue, and dryness of oral mucosa

  • parotid gland enlargement seen in ½ of patients

  • the severity of xerostomia can vary widely from patient to patient

  • Saliva may appear frothy, with lack of usual pooling of saliva in the floor of the mouth

  • tongue often becomes fissured and exhibits atrophy of the papillae

  • Oral mucosa is red and tender and usually results in secondary candidiasis

• Radiographic features of SS

  • often reveal punctate sialectasis and lack of normal arborization of the ductal system, typically demonstrating a “fruit-laden, branching tree”

• Lab values

  • a variety of autoantibodies can be produced, and their presence can be helpful clue in diagnosis

    • a positive rheumatoid factor (RF) is found in approx. 60% of patients, regardless whether the patient has RA

    • Antinuclear antibodies (ANAs) are present 75-85% of patients

    • 2 particular nuclear antibodies- antibody SS-A (anti Ro) and anti SS-B (anti-La) may be found, especially in SS patients

• Treatment

  • mostly supportive

  • dry eyes are best managed by periodic used of artificial tears

  • artificial saliva and sugarless gun or candy can help keep mouth moist

• NOTE

  • about 5% patients with Sjogren syndrome develop lymphoma, an incident that is 40-fold greater than normal

Nomenclature of Tumors (Ch 5. 5-16)

• Benign Tumors

  • Remain localized at their site of origin and are generally amenable to surgical removal

  • Patient generally survives

  • Exceptions arise when benign tumors occur in vulnerable locations such as the brain; here, even "benign" tumors may cause significant morbidity and are sometimes even fatal

  • Naming of benign tumor of mesenchymal cells: "oma" is attached to the name of the cell type from which the tumor arises

    • Chondroma, adenoma, papilloma

• Malignant Tumor

  • Can invade and destroyed adjacent structures and spread to distant sites (metastasize)

  • Collectively called "cancers"

  • Not all cancers peruse a deadly course; some are discovered at early stages that allow for surgical excision, and others are cured with systemically administered drugs or therapeutics antibodies

  • Malignant tumors arising in epithelial cell origin: carcinoma

  • Malignant tumors arising in solid mesenchymal tissues: sarcoma

  • Malignant tumors arising in blood-forming cells: leukemia

• Mixed tumors

  • in most neoplasms, all parenchyma cells closely resemble on another, but some types of tumors more than 1 line of differentiation is evident, creating distinct subpopulation of cells

  • Classic example: mixed tumor of salivary glands (pleomorphic adenoma), which contains epithelial components scattered within myxoid stroma that may contain islands of cartilage and bone

Kawasaki Disease (Ch 8. 65-67)

• Acute, febrile, usually self-limiting illness of infancy and childhood associated with large- to medium-sized vessel arteritis

• 80% < 4-years of age

• Clinical significance stems from involvement of coronary arteries

• Coronary arteritis can result in aneurysms that rupture or thrombose, causing myocardial infarction

• In genetically susceptible people, a variety of infectious agents (mostly virus) have been positioned to trigger the disease

• Presents with conjunctival and oral erythema, blistering edema of hands and feet, erythema of palms and soles, desquamative rash, cervical LN enlargement

• Approx. 20% of untreated patients develop cardiovascular signs and symptoms resulting in asymptomatic coronary arteritis, to giant coronary artery aneurysms

• These aneurysms are associated with rupture, thrombosis, MI, or sudden death

• With IV immunoglobulin therapy and aspirin, the rate of symptomatic disease is < 4%

• Diagnostic Features:

  • Red eyes

  • Coronary artery aneurysms

  • Swollen lymph nodes

  • Peeling of skin

  • Red, dry, cracked lips around fingernails/toenails and inflamed tongue

  • Widespread rash

  • Fever (for more than 5 days)

  • Swelling and/or erythema of palms/soles

Buerger Disease (Thromboaniitis Obliterans) (Ch 8. 71-73)

• Characterized by segmental, thrombosing, acute and chronic inflammation of medium- and small-sized arteries, especially the tibial and radial arteries, that often lead to vascular insufficiencies, typically of the extremities

• Occurs almost exclusively in heavy cigarette smokers

• Usually before the age of 35

• Early manifestations include Raynaud phenomenon, instep foot pain induced by exercise, and a superficial nodular phlebitis

• Vascular insufficiencies tend to be accompanied by severe pain, even at rest, due to neural involvement

• Chronic extremity ulcerations can develop, progressing over time to frank gangrene

• Smoking abstinence in the early stage of the disease can prevent further attacks

• Once established, vascular lesions do not respond to smoking abstinence

Granulomatosis with Polyangiitis (Ch 8. 68-70)

• Previously called Wegener granulomatosis

• Necrotizing vasculitis characterized by a triad of acute necrotizing granulomas of the upper respiratory tract or the lower respiratory tract or both, necrotizing or granulomatous vasculitis affecting small-to-medium-sized vessels, and focal necrotizing, often crescentic, glomerulonephritis

• More common in males; average age of 40 years

• Classic features include bilateral pneumonitis, chronic sinusitis, mucosal ulcerations of the nasopharynx, and renal disease

• Rashes, myalgia, articular involvement, neuritis, and fever can also occur

• If left untreated, the disease is rapidly fatal with 80% mortality within 1 year

• Strawberry gingivitis

Raynaud Phenomenon (Ch 8. 76-80)

• Results from exaggerated vasoconstriction of arteries and arterioles in response to cold or emotion

• It most commonly affects the extremities, particularly fingers and toes

• Occasionally the nose, earlobes, or lips are affected

• Restricted blood flow induces paroxysmal pallor and even cyanosis in severe cases

• Involved digits show "red, white, and blue" color changes

• Primary Raynaud phenomenon affects 3%-5% of the general population

  • in young women

  • occurs symmetrically in the extremities

  • severity and extent of involvement does not progress

• Secondary Raynaud phenomenon refers to vascular insufficiencies due to arterial disease caused by other entities (SLE, scleroderma, Buerger disease, or even atherosclerosis)

  • Asymmetric involvement of extremities

  • progressively worsens over time

• RP may be the first indication of immune-mediated vasculitides, any patient with symptoms should be evaluated

• 10% patients manifest an underlying disorder

Kaposi Sarcoma (Ch 8. 98-100)

• Malignant neoplasm of endothelial cells caused by human herpesvirus 8 (HHV 8; AKA KS herpesvirus)

• It is common in patients with AIDS; its presence is used as a criterion for diagnosis of AIDS

• 4 clinical presentations:

  • Classic

  • Endemic (African)

  • Epidemic (AIDS-related)

  • Iatrogenic (transplant-associated)

• Clinically progress through 3 stages: Patches (red-purple macules), raised plaques and eventually nodular lesions

Atherosclerosis (Ch 8. 34-42)

• Intimal based lesion composed of a fibrous cap and a atheromatous core

• The constituents of the plaque include smooth muscle cells, extracellular matrix, inflammatory cells, calcifications, lipids, and necrotic debris

• Plaques develop and grow slowly over decades

• Atherogenesis is driven by an interplay of vessel wall injury and inflammation

  • stable plaques can produce symptoms related to chronic ischemia by narrowing vessel lumens

  • Unstable plaques can produce fatal ischemic complications related to acute plaque rupture and embolism

• Underlies the pathogenesis of coronary, cerebral, and peripheral vascular disease

• Causes more morbidity and mortality (roughly 1/2 of all death) in the western world than any other disorder

• Major risk factors:

  • Nonmodifiable:

    • genetic abnormalities, family history, increasing age, male gender

  • Modifiable

    • hyperlipidemia, hypertension, cigarette smoking, diabetes, inflammation

• Consequences

  • Major consequences

    • myocardial infarction (heart attack)

    • cerebral infarction (stroke)

    • aortic aneurysm

    • peripheral vascular disease (gangrene of the legs)

  • Large elastic arteries (aorta, carotid, and iliac arteries) and large and medium sized muscular arteries (coronary and popliteal arteries) are the major targets

• Formation and evolution of atherosclerotic plaques

  • the atherosclerotic plaques progress from a fatty streak to a classic atheroma leading to either an erosion or rupture of thin-capped fibroatheroma

  • Atheroma cycles between healing, thrombosis and finally blockage of the concerned artery

  • there could by multiple cycles of healing and rupture before an artery is blocked

Giant Cell (temporal) Arteritis (GCA) (Ch 8. 53-57)

• Chronic, classically granulomatous inflammation of large to small sized arteries that principally affect arteries in the head (T-cell response)

• It is the most common form of vasculitis among elderly adults in the Us and Europe (rare before the age of 50)

• Ophthalmic, vertebral and aorta may be involved

  • ocular symptoms abruptly appear in about 50% patients ( diplopia and blindness); early diagnosis and treatment is vital

  • Temporal arteries are not particularly vulnerable but their name is added to the disorder since they are the most readily biopsied in making diagnosis

• Symptoms are vague and constructional (fever, fatigue, weight-loss) or may involve facial pain and head ache, most intense along the course of superficial temporal artery, which may be painful to palpation

• Diagnosis is based on biopsy and histologic confirmation

  • GCA can be extremely focal within an artery

  • adequate biopsy requires at least 1-cm segment, even then, a negative biopsy result does not include the diagnosis

• Treatment: corticosteroids and anti-TNF therapies are effective

• Lingual necrosis is a rare manifestation of GCA

  • Tongue infarction at second day

  • initial auto-amputation of necrotic tongue at 5th day

  • tongue at 20th day presenting full epithelization

Deep Vein Thrombosis (Ch 8. 87)

• Also known as thrombophlebitis and phlebothrombosis

• deep vein thrombosis account for 90% of cases

• Decreased blood flow in the setting of prolonged immobilization is the most common cause of lower extremity deep vein thrombosis (DVT)

• Can occur with extended bed-rest or sitting during a long airplane ride or automobile excursion

• additional risk factors include pregnancy, oral contraceptive use, obesity, CHF, and malignancy

Lymphedema (Ch 8. 91-92)

• Build-up of fluid in soft tissues when the lymph system is damaged or blocked

• Secondary causes include:

  • Tumors

  • Surgical procedures

  • Post radiation fibrosis

  • Filariasis

  • Post inflammatory thrombosis or scarring

Freckles (Ephelis) (Ch 7. 10)

• Most common pigmented lesions of childhood in lightly pigmented individuals

• Small (one to several mm), tan-red to light brown macules (flat lesions) that appear after sun exposure

• Results from increased amounts of melanin pigment within basal keratinocytes

• Number of melanocytes remain the same

• Once present, they fade and darken in a cyclic fashion during winter and summer, respectively

Melanocytic Nevus (Moles) (Ch 7. 12)

• Benign neoplasms caused in most cases by acquired activating mutations in components of the BRAF or less often, RAS signaling pathways

• Tan to brown, uniformly pigmented, small (< 6mm) relatively flat macules or elevated papules (small round topped elevated lesion) with well-defined, rounded borders

• Nevus cells are rounded cells

• They are from neural crest origin

• Considered to be cousins of melanocytes

Melanoma (Ch 7. 15)

• Most deadly of all skin cancers; highly aggressive; strongly linked to acquired BRAF mutations caused by exposure to UV radiation in sunlight

• In 10%-15% of patients, the risk of melanoma is inherited as an AD trait with variable penetrance

• The A,B,C,D, and E of melanoma

  • Asymmetry: lesions are asymmetric

  • Borders: irregular and often notched

  • Color is variable and not uniform

  • Diameter larger than nevi and is increasing (> 6mm)

  • Evolving; lesions are constantly enlarging, either

    superficially or in a nodular fashion

Seborrheic Keratosis (Ch 7. 18-19)

• Common; occurs most frequently in middle-aged or older individuals

• Arise spontaneously; particularly numerous on trunk

• In people of color, multiple small SK on the face are termed dermatosis papulose nigra (seen in 35% of African-American adults)

• May appear suddenly in large numbers as part of paraneoplastic syndrome (Leser-Trelat sign)

• Round, elevated, coin-like waxy plaque that varies in diameter from mm to several cm; "pasted on" look

• Uniformly tan to dark brown; velvety to granular surface

Acanthosis nigricans (Ch 7. 20-21)

• Thickened, hyperpigmented skin with a velvet-like texture

• Most commonly appears in the flexural areas (axillae, skin folds of the neck, groin-area where upper thighs meets the lowest part of abdomen, and anogenital areas)

• 2 types:

  • In at least 80% cases it is associated with benign conditions and develop gradually; usually during childhood and puberty

  • In 20% of cases, it is associated with cancers; most commonly gastrointestinal adenocarcinoma; usually in middle-aged or older individuals

• Can be an important cutaneous sign of several underlying benign and malignant conditions

Fibroepithelial Polyp (Skin Tag) (Ch 7. 22)

• AKA: acrochordon

• One of the most common cutaneous lesions

• In middle-aged or older individuals; on the neck, trunk, and face

• Soft, flesh-colored, bag-like tumors

• Often attached to the surrounding skin by a slender stalk

• Not uncommon or them to undergo ischemia due to torsion which maycause pain and precipitate their removal

Squamous Cell Carcinoma (Ch 7. 31-32)

• Second most common tumor arising on sun-exposed sites in older people, exceeded only by basal cell carcinoma

• > men (except for lesions of lower legs)

• Usually discovered while small and respectable; < 5% metastasize to regional lymph nodes

• Most common cause is DNA damage induced by exposure of UV light; second most common association is chronic immunosuppression

• Other risk factors include tobacco, betel nut chewing, industrial carcinogens, ionizing radiations, chronic ulcers, and old burn scars

• Stems from multiple driver mutations: TP53, CDKN2A, PIK3CA, KMT2D, and NOTCH1

Basal Cell Carcinoma (Ch 7. 33)

• Distinctive, locally aggressive cutaneous tumor associated with mutations in PTCH1, PTCH2, SMO and SUFU genes

• Most common locally invasive cancers in humans (1 million cases/ year in the US)

• Slow growing; rarely metastasize

• Vast majority recognized in early stages

• Occurs on sun exposed skin; incidence increases in the setting of immunosuppression

• Pearly papules

• Telangiectasia present on papules

Urticaria (Hives) (Ch 7. 45-46)

• Common hypersensitivity reaction

• Usually caused by localized degranulation of mast cells and is uniformly associated with dermal microvasculature hyperpermeability

• Combination of these effects produce pruritic edematous plaques called wheals; Small pruritic papules to large erythematous plaques

• > between ages 20 and 40; all ages are susceptible; > in areas exposed to pressure (trunk, distal extremities, and ears)

• Individual lesions develop and fade within hours (usually, 24 hours); episodes may last for days or persist for months

• Treatment: antihistamines; oral corticosteroids

Psoriasis (Ch 7. 51-52)

• Chronic inflammatory dermatosis that appears to have an autoimmune basis; 1%-2% of US population affected

• Environmental and genetic factors at play

• Persons of all ages affected; approx. 15% of patients have associated arthritis; mild or severe

• > skin of knees, elbows, scalp, lumbosacral areas, intergluteal clefts and glans penis

• Well-demarcated, pink to salmon-colored plaques covered by loosely adherent silver-colored

  scales

• Koebner phenomenon: local trauma can induce lesion in susceptible individuals

Pemphigus (Ch 7. 59-60)

• Blistering disorder caused by autoantibodies (IgG) that result in the dissolution of intercellular attachments (desmoglein) within the epidermis and mucosal epithelium

• > 4-6th decade of life; M = F

• Pemphigus vulgaris most common variant; involves skin and mucosa

• Oral ulcers may persist for years before skin lesion appear

• Primary lesions are vesicles or bullae that rupture easily, leaving shallow erosions

Bullous Pemphigoid (Ch 7. 61-62)

• Caused by autoantibodies that bind to the proteins (hemidesmosomes) that are required for adherence of basal keratinocytes to the basement membrane

• Antibodies deposition occur in a continuous linear pattern at the dermoepidermal junction

• Generally, affects elderly individuals; 10%-15% show oral lesions

• Tense bullae filled with clear fluid involving erythematous or normal appearing skin; , 2 cm in diameter; do not rupture easily

• Heal without scarring

Impetigo (Ch 7. 79-80)

• Common superficial bacterial infection of skin

• Highly contagious; frequently seen in otherwise healthy children as well as occasionally in adults in poor health

• Usually involves exposed skin, particularly that of the face and hands

• Caused by S. aureus

• Erythematous macules with multiple small pustules; as pustules break, shallow erosions form, covered with drying serum giving the appearance of honey colored crust

• If crust not removed, new lesions form on the periphery of the crust

Osteogenesis Imperfecta (brittle bone disease (Ch 9. 12-13)

• Defects in extracellular structural protein

• Most common inherited disorder of connective tissue

• AD; caused by mutations in genes encoding Type 1 collagen

  • Phenotypically heterogenic disorder caused by deficiencies of type 1 collagen synthesis

• Principally affects bone but also impacts other tissues rich in type 1 collagen (joints, skin, teeth, eyes, and ears)

• Characterized by extreme skeletal fragility, blue sclera, hearing loss, and small misshaped, and blue-yellow teeth (secondary to dentin deficiency)

Osteoarthritis and Rheumatoid arthritis (Ch 9. 88-92)

• Arthritis is inflammation of the joints

• clinically, most important forms are:

  • Osteoarthritis

  • Rheumatoid arthritis

Achondroplasia (Ch 9. 10-11)

• Defects in hormones and signal transduction proteins

• the most common skeletal dysplasia and a major cause of dwarfism

• AD disorder

• Gain-of-function in the FGFR3 gene

• Characterized by retarded cartilage growth resulting in shortened proximal extremities, an enlarged head and budging forehead and depression of the root of the nose, and a trunk of relatively normal length

Adrenal cortex hyperfunction/ Cushing syndrome/ Cushing Disease (Ch 11. 13-24, 146-149)

• Corticotropic Adenomas

  • Excess production of the ACTH leads to adrenal hypersecretion of cortisol and the development of hypercortisolism

• Cushing Disease signs and symptoms

  • Moon facies

  • Buffalo hump

  • Truncal obesity

  • Violaceous striae

  • Hirsutism

  • Hypertension

  • Glucose intolerance or diabetes mellitus

  • Visual symptoms if adenoma large

• Cushing Syndrome

  • Disorder caused by conditions that produce elevated glucocorticoid levels

  • Can be broadly divided into:

    • Exogenous: due to corticosteroid therapy prescribed for other medical purposes

    • Endogenous: caused production of adrenocorticotropic hormone by an adrenal adenoma (10%-20% cases) and carcinoma (5% cases)

  • NOTE: If pituitary adenoma is responsible, it is called Cushing disease (70% cases)

    • 4W: 1M

  • Ectopic ACTH may be secreted by small-cell lung Ca

  • Clinical Features

    • Usually develops slowly and onset is subtle

    • The most consistent feature is weight gain, particularly in the central area of the body and hypertension

    • Accumulation of fat in the dorsocervical spine region results in a buffalo hump appearance

    • Fat accumulation in the facial region results in the characteristic rounded facial appearance known as moon facies

  • Other common findings include:

    • Red-purple abdominal striae

    • Hirsutism

    • Mood changes

    • Osteoporosis

    • Hypertension

    • Hyperglycemia with thirst and polyuria

    • Muscle wasting

  • Diagnosis

    • 1. Person receiving large amounts of corticosteroids (greater than the equivalent 20 mg of prednisone) daily for several months

    • 2. Elevated levels of cortisol and low levels of ACTH (ACTH independent CS)

Adrenal Cortex hypofunction/Addison Disease

• Insufficient production of adrenal corticosteroid hormone caused by the destruction of adrenal cortex

• Causes include

  • Autoimmune destruction (most common cause in Western countries)

  • Infections (TB, deep fungal infections, particularly in AIDS patients)

  • Rarely, metastatic tumors, sarcoidosis, amyloidosis, or hemochromatosis

• Clinical features do not begin to appear until at least 90% of the glandular tissue has been destroyed

• With gradual destruction of the adrenal cortex, insidious onset of fatigue, weakness, irritability, depression, and hypotension is noted over period of months

• Generalized hyperpigmentation of skin occurs (bronzing)

  • More prominent in sun-exposed skin and over pressure points

  • Caused by elevated levels of pro- opiomelanocortin (POMC), derived from anterior pituitary and is a precursor of both ACTH and melanocyte stimulating hormone (MSH)

• Oral Manifestations include:

  • Diffuse or patchy, brown, macular pigmentation of the oral mucosa

  • Often the oral mucosal changes are the first manifestation of the disease, with the skin pigmentation occurring afterwards

• In primary hypoadrenocorticism, plasma levels of ACTH are high (>100 ng/L)

• In secondary hypoadrenocorticism the levels are normal (9 to 52 ng/L) or low (due to decreased production of ACTH by the pituitary gland)

• Treatment includes hormone replacement therapy

• Physiologic dose of glucocorticosteroids is approximately 30-45 mg of hydrocortisone or its equivalent, per day, in divided doses

  • Under stressful conditions, the body needs additional hormone

• NOTE: this adjustment is generally not required for dental procedures performed using LA and lasting less than 1 hour

Hypothyroidism+ Hashimoto thyroiditis

• Hypothyroidism:

  • Condition caused by a structural or functional derangement that interferes with the production of thyroid hormone

  • Prevalence increases with age

  • > women (10W;1M)

  • Primary Hypothyroidism

    • Accounts for a vast majority of cases

    • May be:

      • Congenital

      • Autoimmune

      • Idiopathic

  • CRETINISM

    • Refers to hypothyroidism that develops in infancy and early childhood

    • Clinical Features:

      • Severe intellectual disability

      • Short stature

      • Coarse facial features

      • Protruding tongue

      • Umbilical hernia

  • MYXEDEMA

    • Hypothyroidism development in the older child or adult

    • Clinical findings

      • Early symptoms include generalized fatigue, apathy, and mental sluggishness which mimics depression

      • Speech and intellectual functions are slowed

      • Patients are listless, cold intolerance, and frequently overweight

      • Skin is cold

      • Reduced cardiac output

  • HYPOTHYROIDISM LAB FINDINGS

    • Lab values play a vital role in diagnosis of suspected hypothyroidism because of nonspecific nature of symptoms

    • TSH levels are increased in primary hypothyroidism

    • TSH levels are not increased if hypothyroidism takes place at the pituitary or hypothalamus levels

    • Measurement of serum TSH levels is the most sensitive screening test for this disorder

• Hashimoto Thyroiditis

  • Autoimmune disease

  • Results in destruction of the thyroid gland and gradual and progressive thyroid failure

  • Prevalence between 45 and 65 years of age

  • > women (10:1)

  • Pathogenesis

    • Caused by a breakdown in self-tolerance to thyroid autoantigens

    • Predisposition has a strong genetic component

  • Clinical Features

    • Painless enlargement of the thyroid gland associated with some degree of hypothyroidism

    • > in middle-aged women

    • Enlargement symmetric and diffuse

    • Incidences are at an increased risk for developing other autoimmune disease

    • They are also at an increased risk of B-cell lymphoma

  • Lab Values

    • Fall in serum levels to T3 and T4

    • Compensatory increased serum TSH

Hyperthyroidism/ Graves Disease

• Lab Findings for hyperthyroidism

  • Low TSH values accompanied by increase in free T4 levels

  • NOTE: measurement of serum TSH concentration is the most useful single screening test for hyperthyroidism)

  • In occasional patients, hyperthyroidism results predominantly from increased circulatory levels of T3 (T3 toxicosis); in these cases, free T4 levels may be decreased

• Treatment

  • 1. Beta blockers to control symptoms

  • 2. Thionamide to block new hormone synthesis

  • 3. An iodine solution to block the release of thyroid hormone

  • 4. Radioactive iodine, which is incorporated into thyroid tissues resulting in ablation of thyroid function over a period of 6 to 18 weeks

• Graves Disease

  • Autoimmune disorder

  • Peak incidence between 20 and 40 years of age

  • > women (10:1)

  • Characterized by the production of autoantibodies against multiple thyroid proteins most importantly the TSH receptors

  • Most common cause of endogenous hyperthyroidism

  • Characterized by a triad of clinical findings

    • Hyperthyroidism associated with diffuse enlargement of the gland

    • Infiltrative ophthalmopathy and resultant exophthalmos

    • Localized, infiltrative dermopathy, sometimes called pretibial myxedema, which is present in a minority of patients

  • Lab Values

    • Elevations in serum levels to T3 and T4

    • Decreased serum TSH

  • Treatment

    • Treated by beta blockers (dampened symptoms related to increased sympathetic nervous system activity)

    • Radioiodine ablation

    • Thyroidectomy

Aphthous Ulcers

• Common, often recurrent, and painful

• Cause is unknown; affect 40% of the population

• Most frequent in the first two decades of life

• Tend to be clustered within some families and may be associated with immunological disorders including celiac disease, inflammatory bowel disease, and Bechet syndrome

• Lesion may be single or multiple, shallow, mucosal ulcerations covered by a thin exudate and rimmed by a narrow zone of erythema; seen on nonkeratinized mucosa

• Lesions resolve spontaneously in 7-10 days but sometimes persist for weeks, particularly in immunocompromised patients

Fibroma

• Submucosal nodular mass of fibrous connective tissue stroma

• > on buccal mucosa along bite line or gingiva

• Reactive process induced by repetitive trauma

• Treatment is complete surgical excision

Pyogenic Granuloma (Pregnancy Tumor)

• Exophytic inflammatory lesion

• > gingiva (75%); > in children, young adults, and pregnant women

• Red to purple in color and frequently ulcerated

• In some cases rapid growth is alarming and elicit concern of malignancy

• Histologically, they are highly vascularized proliferation of organizing granulation tissue

• PG can regress, mature into dense fibrous masses, or develop into peripheral ossifying fibroma

• Treatment is complete surgical excision

Peripheral Ossifying Granuloma

• Reactive growth

• Occurs exclusively on the gingiva

• > young females (10-19 years of age)

• Some arise in long-standing PG, and others develop de novo from cells of the periodontal ligament

• POF appears as a red, ulcerated nodular lesion

• Treatment is complete surgical excision down to the periosteum is required

• Recurrence rate of 8% to 16%

Oral Hairy Leukoplakia

• Distinctive oral lesion on the lateral border of the tongue caused by Epstein Barr Virus that usually occurs in immunocompromised patients

• In patients infected with HIV, OHL may portend development of AIDs

• OHL are increasingly seen in patients who are immunocompromised for other reasons including cancer therapy, transplant-associated immunosuppression and old age

• Clinically, white linear lines or hyperkeratotic thickenings are seen on the lateral border of the tongue; they cannot be scraped off

Burkitt lymphoma

• A B-cell neoplasm; two types:

  • Endemic

  • Sporadic

  • Immunodeficiency associated: occurs in HIV + patients and in organ transplant patients

• It may be the fastest growing human neoplasm

• Characterized by the translocation and deregulation of the MYC gene on chromosome 8; t(8;14)

• Endemic BL:

  • Seen in parts of Africa

  • Often presents with massive involvement of maxilla and mandible

  • Common in children aged 4 to 7 who have malaria and Epstein- Barr virus

• Sporadic BL:

  • Seen worldwide

  • Involves the abdomen area

  • 60% over the age of 40 years; 40% children

  • Account for 1-2% of adult lymphoma cases

• Despite its fast-growing nature, Burkitt lymphoma is one of the most curable forms of non-Hodgkin lymphoma

• More than 90% of children with localized tumors and more than 85% with widespread disease are cured

• Extra:

  • Jackie Kennedy Died of Non- Hodgkin Lymphoma

Multiple Myeloma

• Uncommon, clonal and malignant plasma cell proliferative disorder

• Characterized by the abnormal increase of monoclonal immunoglobulins

• Consequences of undiagnosed disease are severe leading to:

  • Hypercalcemia

  • Renal dysfunction

  • Anemia

  • Bone pain accompanied by lytic lesions

• Etiology unknown

  • Frequent alterations and translocations in the promoter genes, especially chromosome 14

  • Other oncogenes such as NRAS, KRAS, and BRAF may participate in plasma cell proliferation

• Median age at diagnosis of about 70 years

• Slightly more commonly seen in males than females

• Increased incidence in African American and black populations by as much as two-fold compared to White

• Clinical Features:

  • Quite variable; typically more subacute and insidious in onset

  • Can present with severe symptoms

• Symptoms:

  • Hypercalcemia (C)

  • Renal dysfunction (R)

  • Anemia (A)

  • Bone pain with lytic lesions "punched out lesions" (B)

• Cells produce abnormal clonal, complete or incomplete, immunoglobulins

• Abnormal immunoglobulin, usually a light chain, was previously referred to as Bence-Jones protein

• Dental Manifestations

  • Poor healing

  • Jawbone involvement

  • Bleeding tendency

  • Infections

  • Pain and paresthesia

• Patients often on IV bisphosphonates- results in medication-related osteonecrosis of bone (MRONJ)

• Prognosis depends on the stage of the disease

Hodgkin Lymphoma

• A rare monoclonal B-cell lymphoid neoplasm characterized by the following four features:

  • Usually presents in young adults

  • Commonly arises in cervical lymph nodes

  • Involves scattered large mononuclear Hodgkin and multinucleated Reed-Sternberg cells on a background of non-neoplastic inflammatory cells

  • Characteristic neoplastic cells are often surrounded by T lymphocytes

• Divided into two distinct categories that demonstrate different pathologic and clinical features:

  • Classical HL: accounts for approx. 95% of HL; further subdivided into 4 subgroups

    • Nodular sclerosis (NSHL)

    • Lymphocyte-rich (LRHL)

    • Mixed cellularity (MCHL)

    • Lymphocyte-depleted (LDHL)

  • Nodular lymphocyte-predominant HL (NLP- HL)

• It has a bimodal distribution

• Most of the affected patients are between ages 20 to 40 years

• There is another peak from age 55 years and older

• seen more in males

• Oral manifestations

  • Patients treated with radiation may have dry mouth if submandibular and sublingual glands are in the field

  • Need prophylactic fluoride gel, varnish or toothpaste to prevent dental caries

Langerhans Cell Histiocytosis

• Idiopathic condition

• Characterized by proliferation of abnormal Langerhans (antigen-presenting) cells

• Has characteristics of both an abnormal reactive process and a neoplastic process

• Lower antigen presenting capabilities

• Rare; 1 to 2 newborns per million per year

• May occur at any age but is more likely to occur in those <15 years of age

• Unknown etiology

• Symptoms depend on organ involvement at the time of presentation

  • Rash is the most common presentation; single lesion or widespread involvement

  • Bony involvement occurs in about 78% of patients

  • Pulmonary lesions occur in 20% of patients

  • LN involved in 20% of patients; pulmonary symptoms or lymphadenopathy

  • Pituitary gland involvement causes diabetes insipidus

• Prognostic Categories

  • Classification:

    • Single organ involvement

      • Unifocal disease

      • Multifocal disease

    • Multiorgan involvement

      • No organ dysfunction

      • Organ dysfunction

        • Low-risk (skin, LN, bone, and/or pituitary gland)

        • High risk (lung, liver, spleen, and/or bone marrow)

• Traditional Clinical Classifications

  • Monostotic or polyostotic eosinophilic granuloma:

    • Solitary or multiple bone lesions without visceral involvement

  • Chronic disseminated histiocytosis (Hand-Schuller-Christian disease):

    • Involves skin, bone, and viscera

  • Acute disseminated histiocytosis (Letterer-Siwe disease):

    • Prominent cutaneous, visceral, and bone marrow involvement mainly in infants

• Hand-Schuller-Christian Disease

Hemophilias

• Factor VIII Deficiency

• Factor IX deficiency

• Von Willibrand Disease

Hemophilia

• A medical condition in which the ability of the blood to clot is severely reduced, causing the patient to bleed severely from even a slight injury

• The condition is typically caused by a hereditary lack of a coagulation factor, most often factor VIII

Factor VIII Hemophilia (Classic Hemophilia/ Hemophilia A)

• Factor VIII is one of the essential blood proteins and plays a role in aiding the blood to clot in response to injury

• Mutations of the F8 gene result in deficient levels of functional factor VIII

• X-linked recessive trait; 30% are new mutations and do not have a family history

• Accounts for 80% of hemophilias

• Occurs in males; rarely, homozygous females affected

• Called the Royal Disease since it appeared in one of Queen Victoria’s sons and was propagated in her descendants

• Factor VIII Deficiency Clinical Features

  • Easy bruising

  • Massive hemorrhage after surgery or trauma

  • Hemorrhage into joints (hemarthroses) may eventually result in deformity

• Petechiae and ecchymoses are characteristically absent

• Treatment: factor VIII infusions after injury or before surgery

Factor IX Deficiency (Hemophilia B/ Christmas Disease)

• X-linked recessive transmission

• Clinically resembles Factor VIII deficiency

• Much less common

• Usually not as severe as Factor VIII deficiency

Von Willebrand Disease

• A bleeding disorder caused by the qualitative or quantitative deficiency of the von Willebrand factor

  • Von Willebrand factor necessary for proper platelet adhesion to damaged blood vessels

  • It is a carrier for Factor VIII as well protecting it from degradation

• Affected people may complain of:

  • Excessive bruising

  • Prolonged bleeding from mucosal surfaces

  • Prolonged bleeding after minor trauma

• Clinical Features

  • Usually, mild symptoms

  • Women may have heavy menstrual periods

  • Often underdiagnosed

  • Most common inherited bleeding disorder

  • AD or AR

  • Thus, both men and women can have it in about equal

Angina Pectoris

• Angina Pectoris is temporary chest pain or discomfort caused by the inability of diseased coronary arteries to deliver sufficient oxygen-laden blood to heart muscles

  • It is a sign of increased risk of heart attack

• Triggered by emotional stress, physical exercise, exposure to very hot or cold temperatures, smoking, eating a heavy meal

• Symptoms

  • pressure or pain in the center of the chest that may radiate to the shoulder, arm, back, neck, and jaws

  • some patients may describer them as like the sensation of having indigestion or gas

• Types

  • stable angina

  • prinzmetal

  • Unstable angina

Stable angina pectoris

• Stable Angina Pectoris is associated with fixed atherosclerotic narrowing of one or more coronary arteries

• Discomfort in the chest described as deep, poorly localized pressure, squeezing, or burning sensation (like indigestion), but usually as pain

• Produced by physical activity, emotional excitement, or physiological stress

• Pain relieved by rest and/or nitroglycerin or calcium channel blockers

Prinzmetal angina pectoris

• Prinzmetal Angina Pectoris is anginal pain occurring at rest or awakening patient from sleep

• Usually associated with coronary artery spasm often adjacent to a site of atherosclerotic plaque

• Mechanism underlying spasm poorly understood

Unstable Angina pectoris

• increased frequency of angina episodes

• Precipitated by progressively less exertion

• Described as intense pain

• More intense and lasts longer than stable angina (>20 minutes)

• Induced by acute plaque change with a superimposed partial thrombosis or vasospasm or both

Angina pectoris Treatment

• Nitroglycerin (oral medication classified as a vasodilator)

  • patients take nitroglycerin about 10 minutes before they begin doing an activity that will likely trigger symptoms

Myocardial Infarction

• Myocardial Infarction (heart attack) is the irreversible necrosis of heart muscle secondary to prolonged ischemia

• Etiology: closely associated with coronary artery disease

• Common symptoms include

  • chest discomfort

  • shortness of breath

  • discomfort in the upper body

• Myocardial necrosis begins within 20-30 minutes of infarction and reaching full size within 3-6 hours

• Begins in subendocardium extending toward epicardium

• Thrombolytic agents (tissue plasminogen activator t-PA) may limit size of infarct during this time frame

  • Thrombolytic drugs: Eminase, retavase, streptase activase

  • Note: Aspirin is not thrombolytic, but may limit clot size- antiplatelet adhesion drug

• Clinical complications of acute MI include

  • sudden death

  • cardiogenic shock

  • cardiac arrhythmias

  • cardiac tamponade due to cardiac rupture

• Anatomic complications of MI include

  • valve insufficiency due to infarcted papillary muscle

  • ventricular aneurysms

  • mural thrombus giving rise to systemic arterial emboli

  • cardiac tamponade due to rupture of the infarcted area of the heart

• Myocardial infarction treatment

  • reperfusion therapy is indicated in all patients with symptoms of ischemia of less than 12-hours duration

  • Nitrates: IV nitrates are more effective than sublingual nitrates (giving rise to nitric oxygen, which causes vasodilation-nitroglycerine)

  • Beta-blockers (reduces myocardial workload, and thus oxygen demant, via reduction in heart rate and BP)(olol’s- atenolol, bisoprolol)

  • lipid lowering treatment (statins)

  • Antithrombotic therapy (aspirin)

Pleural Tumor - Mesothelioma

• Malignant mesothelioma

  • 50% have a history of asbestos exposure

  • 25-40 yrs. latent period

  • Asbestos not used since 1960

  • No direct link between smoking and mesothelioma

• Essentially incurable unless detected at a limited stage

  • Median survival 11 months

Sarcoidosis

• Systemic granulomatous disease of unknown cause that may involve many tissues and organs

• Histologic feature: formation of noncaseating granulomas

• Clinical manifestations include LN enlargement, eye involvement (dry eyes, iritis), skin lesions (erythema nodosum), and visceral (liver, skin, marrow) involvement

• Lung involvement occurs in 90% of cases with formation of granulomas and interstitial fibrosis

• Highest incidence in African American (10 X) and Scandinavians

• Adults between 30 and 50 years of age

  • Papular sarcoidosis as a cutaneous manifestation seen on the upper back region. Multiple erythematous raised lesions are evident

  • Plaque sarcoidosis as a cutaneous manifestation seen on the upper arms. Multiple erythematous plaques are evident

  • Uveitis

    • Inflammation in the middle layer of the eye, called the uvea

• Sarcoidosis Treatment

  • Two fundamental facts that exert heavy influence on the management of sarcoidosis

    • 1. Frequently undergoes spontaneous regression without causing any permanent damage to the affected organs

    • 2. Glucocorticoids, is the cornerstone for treatment (associated with several serious adverse effects)

  • Treatment is indicated only when symptoms are disabling and/or the granulomatous inflammation is relentlessly progressive, causing life- or organ-threatening disease

• Sarcoidosis Oral Cavity

  • Lesions are a rare occurrence; may be the first presenting sign of the disease

  • May involve gingiva or other oral locations

  • Lesions present as:

    • Localized swelling

    • Nodules

    • Ulcers

    • Gingivitis

    • Gingival hyperplasia

    • Gingival recession

Hepatitis