Homework

Epidemiology

Time Course

Clinical Presentation with Classic S&S

Mechanism of Disease Process

Define: Herpes zoster (HZ) or shingles, is the reactivation of the latent varicella zoster virus (VZV) or chicken pox, in the dorsal root ganglia (Sandy, 2005).

Demographics: People over the age of 60 who had the chicken pox or varicella vaccine.

Risk Factors: Those who had the natural infection of varicella-zoster virus, varicella vaccination, malignancies such as lymphoma or leukemia, bone marrow and solid organ transplant, HIV with CD4 count <200 cells/microL, cancer chemotherapy, corticosteroid therapy, immune-modulatory therapy, or over the age of 60.

Incidence: 4 cases per 1,000 U.S. population annually (Center for Disease Control and Prevention [CDC], 2016).

Exposures: Close contact with ill persons

Duration of Prodromal Symptoms: The pre-eruptive phase can last 1-10 days with an average of 48 hours (Sandy, 2005).

Pattern of Prodrome or Symptoms: The eruptive phase is next marked by the emergency of vesicular eruptions resolves in 10-15 days. The chronic phase is characterized by persistent or recurring pain lasting 30 or more days after the lesions have crusted, which occurs in 9-45% of all cases (Sandy, 2005).

Symptoms: Muscle or toothache like pain, fever, loss of appetite, rash that is painful, itchy or tingly, headache, sensitivity to light, malaise (CDC, 2016).

Signs: Itching or burning pain and paresthesia or puritis lasting from one day to three weeks, followed by a maculopapular vesicular rash on an erythematous base. The rash is most commonly confined to the thoracic region at the fifth and sixth dermatome levels in a belt like fashion and distributed in irregular groupings of vesicles that vary in size and do not cross the midline of the body (Sandy, 2005).

Must-Have Features: Rash appearance and distribution are unilateral and vesicular on an erythematous base and confined to the thoracic region.

Rejecting Features: Dermatomal pain without rash, rash eruption affecting bilateral dermatomes (Sandy, 2005).

Diagnostics: Tzanck viral culture smear to differentiate VZV from herpes simplex virus, fluid culture for VZV DNA by polymerase chain reaction to differentiate wild type from vaccine virus, or VZV immunohistochemistry by immunoglobulin M and immunoglobulin G antibody testing to differentiate the presence of acute or previous infection (Sandy, 2005).

Pathophysiology: VZV viral particles remain dormant in the dorsal root and cranial sensory ganglia after infection or vaccination. Immunologic mechanisms suppress replication of the virus, but VZV reactivate when the host fails to contain the virus. Once VZV is activated at the spinal root or cranial nerve neurons, an inflammatory response occurs. This inflammation in the dorsal root ganglion causes hemorrhagic necrosis of nerve cells, leading to neuronal loss and fibrosis. The virus then travels from the sensory ganglion back down the nerve to the skin, where it produces the characteristic dermatomal rash of herpes zoster (Sandy, 2005).

Known Derangements: Declining virus-specific cell mediated immune responses due to aging causes the body to lack the ability to suppress replication of the virus. With weakening of VZV-specific cellular immunity due to immunosuppression the virus may reactivate and travel peripherally along sensory nerves to reach the mucocutaneous surface that is innervated by the ganglia in which the virus is reactivated (Sandy, 2005).

Epidemiology

Time Course

Clinical Presentation with Classic S&S

Mechanism of Disease Process

Define: Ichthyosis is a family of disorders characterized by dry or scaly and thickened skin (National Institute of Arthritis and Musculoskeletal and Skin Disease [NIAMS], 2012). There are more than 20 types of ichthyosis, but Ichthyosis Vulgaris is the most common type affecting 95% of patients who have this skin disease.

Demographics: Presents in early childhood-usually from 3 months to 5 years of age and more common in Europeans.

Risk Factors: Inherited genes for ichthyosis from one or both parents or develop a gene mutation for ichthyosis while in the womb (American Academy of Dermatology, 2016).

Incidence: A common disease in the U.S., with a prevalence of 1 case in 300 persons (American Academy of Dermatology, 2016).

Exposure: Hereditary

Pattern of Symptoms: Absent at birth, typically appears within the first year of life to five years, intensifying up until puberty then decreases with age (NIAMS, 2012).

Symptoms: Dry skin, itchy skin, flaky scalp, tile-like small scales, and deep, painful cracks in skin

Signs: Scales that are white, gray, or brown appearing on the fronts of legs, backs of arms, scalp, or abdomen typically, thickened skin on the palms and soles, deep cracks on the palms and soles, puritis, keratosis pilaris, and decreased ability to sweat causing temperature dysregulation (American Academy of Dermatology, 2016).

Must-Have Features: Hyperkeratosis and onset in infancy or early childhood

Rejecting Features: Skin takes on a “dry river bed” appearance with inflammation, or fine, silvery scale.

Diagnostics: Genetic testing

Pathophysiology: Ichthyosis vulgaris is caused by a loss-of-function mutation in the gene encoding the protein filaggrin. This mutation leads to defection production of filaggrin. Filaggrin is a filament-associated protein require for the binding of keratin fibres in epidermal cells to form an effective skin barrier. It helps to maintain the skin pH, retain moisture, and reduce trans-epidermal water loss. Dryness results from the reduced skin hydration due to the defective filaggrin. Excessive scales are caused by the inability of the skin cells to remain hydrated as they move upward through the stratum coreum. Hyperkeratosis results from compensatory repair mechanisms increasing cell proliferation (NIAMS, 2012).

Known Derangements: Autosomal dominant genetic disorder leading to defective production of filaggrin. Symptoms worsen in the winter months due to decreased moisture from the cold, dry air.

Epidemiology

Time Course

Clinical Presentation with Classic S&S

Mechanism of Disease Process

Define: Erythema multiforme is a skin condition considered to be a hypersensitivity reaction associated with certain infections and medications (Lamoreux, Sternbach, & Hsu, 2006).

Demographics: Typically occurs in adults 20 to 40 years of age, but it can occur at any age.

Risk Factors: Herpes simplex virus infection, mycoplasma pneumonia, hepatitis B virus infection, fungal infections, HIV infection, lymphoma, hepatitis B vaccine, allergic response to tattoos, syphilis, cytomegalovirus infection, Epstein-Barr virus, and medications such as barbiturates, anticonvulsants, penicillin, phenothiazine, hydantoins, and NSAIDs (Lamoreux, Sternbach, & Hsu, 2006).

Exposures: Close contacts with ill persons, tattoos, and vaccinations.

Duration of Prodromal Symptoms: Typically, no prodromal symptoms.

Pattern of Symptoms: Target lesions appear 7 days after the onset of itching and/or burning at the site of eruption, and then resolves spontaneously in three to five weeks.

Symptoms: Red spots, ridges, and sometimes blisters appear on the tops of hands, forearms, face, neck, legs, or trunk, some spots may evolve into concentric circles that resemble a target with a grayish discoloration in the center, muscular stiffness, fever, and malaise may occur.

Signs: The individual lesions begin acutely as numerous sharply demarcated red or pink macules that then become papular. The papules may enlarge gradually into plaques several centimeters in diameter. The central portion of the papules gradually becomes darker red, brown, dusky, or purpuric. Crusting or blistering sometimes ensues in the center of the lesions. The characteristic “target” or “iris” lesion has a regular round shape and three concentric zones: a central dusky or darker red area, a paler pink or edematous zone, and a peripheral red ring. The skin lesions of erythema multiforme usually appear symmetrically on the distal extremities and progress proximally. Lesions on the dorsal surfaces of the hands and extensor aspects of the extremities are most characteristic. Palms and soles also may be involved (Lamoreux, Sternbach, & Hsu, 2006).

Must Have Features: Individual lesions are present and in a fixed location for at least one week and some evolve into target lesions.

Rejecting Features: Lesions at the same site for less than 24 hours, center of the lesions appears normal, target lesions with dusky or purpuric center, or bullous lesions.

Diagnostics: No specific laboratory tests or biopsies are indicated to make the diagnosis of erythema multiforme.

Pathophysiology: The pathophysiology of erythema multiforme is still not completely understood but it is thought to be immunologically mediated and involves a hypersensitivity reaction that can be triggered by stimuli such as bacterial, viral, or chemical products (Lamoreux, Sternbach, & Hsu, 2006).

Known Derangements: Herpes associated erythema multiforme is thought to be due to a delayed type hypersensitivity reaction. The disease begins with the transport of viral DNA fragments to distant skin sites by peripheral blood mononuclear cells. HSV genes within DNA fragments are expressed on keratinocytes, leading to the recruitment of HSV-specific CD4 helper T cells involved in cell-mediated immunity. The CD4 cells react to viral antigens with production of interferon-γ, starting an inflammatory cascade (Lamoreux, Sternbach, & Hsu, 2006). Patients taking medications such as barbiturates, anticonvulsants, penicillin, phenothiazine, hydantoins, and NSAIDs that develop erythema multiforme often have an altered metabolism of the responsible drug and are considered to be slow acetylators. This means that an increased proportion of drug metabolism is directed toward the alternative pathway of oxidation by the cytochrome P-450 system, causing in increased production of reactive and possibly toxic metabolites. Affected individuals have a defect in the ability to detoxify these reactive metabolites, which may then behave as happens by binding covalently to proteins on the surface of epithelial cells. This may then induce the immune response, leading to the severe skin reaction (Lamoreux, Sternbach, & Hsu, 2006).

Epidemiology

Time Course

Clinical Presentation with Classic S&S

Mechanism of Disease Process

Define: Melanoma is the tumor of melanin-forming cells, typically a malignant tumor associated with skin cancer (American Cancer Society, 2016).

Demographics: White, male> females, and over the age of 60.

Incidence: About 87,110 new melanomas will be diagnosed (about 52,170 in men and 34,940 in women). About 9,730 people are expected to die of melanoma (about 6,380 men and 3,350 women) (American Cancer Society, 2016).

Risk Factors: Sun exposure, moles, fairer skin, blue or green eyes, freckles, blonde or red hair, immunocompromised, family history of melanoma, genetic mutations to genes associated with melanoma, history of basal or squamous cell skin cancers, and older age

Exposures: Indoor tanning bed, not applying sunscreen when in the sun, and living in an area with a warmer climate and more UV light.

Pattern of Symptoms: Melanomas have two growth phases, radial and vertical. During the radial growth phase, malignant cells grow in a radial way in the epidermis. With time, most melanomas progress to the vertical growth phase, in which the malignant cells occupy the dermis and develop the ability to metastasize (American Cancer Society, 2016).

Classifications for melanomas are called stages. The stage refers to the thickness, depth of penetration, and the degree to which the melanoma has spread. The staging is used to determine treatment. Early melanomas (Stages 0 and I) are localized; Stage 0 tumors are in situ, meaning that they are noninvasive and have not penetrated below the surface of the skin, while Stage I tumors have invaded the skin but are small, non-ulcerated, and are growing at a slow mitotic rate. Stage II tumors, though localized, are larger (generally over 1 mm. thick) and/or may be ulcerated or have a mitotic rate of greater than than 1/mm2; they are considered intermediate melanomas. More advanced melanomas (Stages III and IV) have metastasized to other parts of the body. There are also subdivisions within stages (Skin Cancer Foundation, 2017).

Symptoms: New spot on the skin or a spot that is changing in size, shape, or color, spot that looks different from all other spots on your skin.

Signs: A is for Asymmetry: One half of a mole or birthmark does not match the other. B is for Border:  The edges are irregular, ragged, notched, or blurred. C is for Color:  The color is not the same all over and may include different shades of brown or black, or sometimes with patches of pink, red, white, or blue. D is for Diameter:  The spot is larger than 6 millimeters across (about ¼ inch – the size of a pencil eraser), although melanomas can sometimes be smaller than this. E is for Evolving: The mole is changing in size, shape, or color (American Cancer Society, 2016).

Must Have Features: Abnormal skin area with one or more signs that is confirmed with a positive skin biopsy.

Rejecting Features: Negative skin biopsy

Diagnostics: Skin exam & skin biopsy

Pathophysiology: Melanomas begin from melanocytes, which emerge from the neural crest and travel to the epidermis, uvea, meninges, and ectodermal mucosa. The melanocytes, which live in the skin and produce a protective melanin, are contained within the basal layer of the epidermis, at the junction of the dermis and epidermis. Melanomas may develop in or near a previously existing precursor lesion or in healthy-appearing skin. A malignant melanoma developing in healthy skin is said to arise de novo, without evidence of a precursor lesion. Many of these melanomas are stimulated by solar irradiation (Skin Cancer Foundation, 2017).

Known Derangements: Many genes are implicated in the development of melanoma, including CDKN2A (p16), CDK4, RB1, CDKN2A (p19), PTEN/MMAC1, and ras. CDKN2A (p16) appears to be especially important in both random and hereditary melanomas (American Cancer Society, 2016). Exposure to ultraviolet radiation (UVR) is a serious factor in the development of most melanomas. Ultraviolet A (UVA), wavelength 320-400 nm, and ultraviolet B (UVB), 290-320 nm, possibly are carcinogenic and actually may work in concert to induce a melanoma.

UVR appears to be an effective inducer of melanoma through many mechanisms, including suppression of the immune system of the skin, generation of melanocyte cell division, free radical production, and damage of melanocyte DNA (Skin Cancer Foundation, 2017).

Epidemiology

Time Course

Clinical Presentation with Classic S&S

Mechanism of Disease Process

Define: Vasculitis is a term for a group of rare diseases that have in common inflammation of blood vessels. These vessels include arteries and veins. When such inflammation occurs, it causes changes in the walls of blood vessels, such as weakening and narrowing that can advance to the point of blood vessel blockage. A result of vasculitis is that the tissues and organs supplied by affected blood vessels do not get enough blood. This can cause organ and tissue damage that can even lead to death (Hasan, 2017). Giant cell arteritis (GCA) is the most common form of vasculitis. In GCA, the vessels most often involved are the arteries of the scalp and head, especially the arteries over the temples, which is why another term for GCA is “temporal arteritis.”

Demographics: Whites> non-whites, women> men, and over the age of 50.

Incidence: Data from population-based studies estimate that 1 in 5,000 people over the age of 50 years are affected by GCA each year.  The prevalence of GCA is estimated at 278 per 100,000 people over the age of 50 years (Hajj-Ali, 2012).

Risk Factors: Over the age of 50, women, Northern European descent, polymyalgia rheumatic, and family history.

Exposures: Age

Prodromal Symptoms: May occur for a few days to weeks

Pattern of Symptoms: Chronic and worsening if not treated

Symptoms: Headache around the temples, pain in jaw muscle while chewing, decreased appetite, tenderness of the scalp, vision changes, and shoulder or hip joint aching and stiffness

Signs: Low grade temperature, weight loss, polymyalgia rheumatic, swelling or decreased pulses in the temporal artery, tenderness to pressure on the carotid artery, generalized tenderness, jaw claudication, and blurred vision

Must Have Features: One or more symptom and a superficial temporal artery biopsy that shows inflammation

Rejecting Features: No inflammation present in the temporal arteries

Diagnostics: Elevated erythrocyte sedimentation rate and C-reactive protein levels, elevated platelet counts, positive temporal artery biopsy (Hajj-Ali, 2012).

Pathophysiology: GCA is an autoimmune disorder causing immune cells to be involved in an inflammatory reaction. The primary inflammatory response involves the activation of dendritic cells in the adventitia of arteries by an unknown antigen, with production of chemokines that recruit CD4+T helper cells. Activated CD4+ T helper cells differentiate into Th1 cells (producing interferon gamma) and Th17 cells (producing interleukin 17).

Interferon gamma causes endothelial cells and vascular smooth muscle to recruit more Th1 cells, CD8+ T cells, and monocytes. The monocytes differentiate into macrophages and the characteristic giant cells that produce growth factors, other interleukins and proteolytic enzymes that increasingly narrow and obstruct the vessel wall. Narrowing of the blood vessel lumen causing decreased blood supply to the neighboring tissues.  The blood vessel may also become thrombosed causing severe ischemia or necrosis of tissues ordinarily supplied by the blood vessel (Hajj-Ali, 2012).

Known Derangements: A cellular immune reaction to elastin has been associated in the pathogenesis of GCA. In support of the hypothesis that elastin is the inciting antigen, disease severity has been shown to correlate with the amount of elastic tissue within the vessels (Hajj-Ali, 2012).

Epidemiology

Time Course

Clinical Presentation with Classic S&S

Mechanism of Disease Process

Define: acute, nodular, erythematous eruption that usually is limited to the extensor aspects of the lower legs (Schwartz & Nervi, 2007).

Demographics: Women> men, more common in young adults 18-34 years

Incidence: erythema nodosum occurs in approximately one to five per 100,000 persons (Schwartz & Nervi, 2007).

Risk Factors: Streptococcal infections, inflammatory bowel disease, sarcoidosis, Hodgkin disease and lymphoma, pregnancy, sulfonamides and halides.

Exposures: Working in close contact with the ill, and recent streptococcal

infection

Pattern of Symptoms: A prodrome commonly occurs as early as one to three weeks before the onset of erythema nodosum. Individual nodules may last for two weeks; new outcroppings may continue to develop for up to six weeks. These nodules often take approximately one to two months to heal completely and may assume a bruise-like appearance as they fade. The active disease may last up to 18 weeks (Schwartz & Nervi, 2007).

Symptoms: Fever, malaise, painful, symmetric, red nodules on the anterior leg

Signs: Lesion borders are poorly defined, and lesions vary from 2-6 cm. During the first week, lesions become tense, hard, and painful; during the second week, they may become fluctuant, as in an abscess, but do not weep or ulcerate. Individual lesions last approximately 2 weeks, but occasionally, new lesions continue to appear for 3-6 weeks. Lesions change color in the second week from bright red to bluish or livid. As absorption progresses, the color gradually fades to a yellowish hue, resembling a bruise. Aching legs and swelling ankles may continue for weeks. Hilar adenopathy may develop as part of the hypersensitivity reaction of erythema nodosum. Arthralgia occurs in more than 50% of patients and begins during the eruptive phase or precedes the eruption by 2-4 weeks. Erythema, swelling, and tenderness occur over the joint, sometimes with effusions. Joint tenderness and morning stiffness may occur (Schwartz & Nervi, 2007).

Must Have Features: Symmetrical nodular red lesions with poorly defined borders

Rejecting Features: Lesions that weep, lesions that appear for less than 2 weeks, lesions that do not change color over time to appear like a bruise, and vasculitis

Diagnostics: CBC with differential, evaluation for streptococcal infection, excisional biopsy showing septal panniculitis (Schwartz & Nervi, 2007).

Pathophysiology: Erythema nodosum is a nonspecific cutaneous reaction pattern to a variety of antigens, with many immune-mediated mechanisms involved. Most direct and indirect evidence supports the involvement of a type IV delayed hypersensitivity response to numerous antigens (Schwartz & Nervi, 2007). The exact pathophysiology is not known today.

Known Derangements: Ulcerative colitis and Crohn disease may cause erythema nodosum. Erythema nodosum associated with enteropathies correlates with flares of the disease. Erythema nodosum occurs in up to 4.6 percent of women who are pregnant, possibly as a result of estrogen production or relative levels of estrogen and progesterone. Estrogen also has been suggested as the linking factor behind the adult male-to-female incidence ratio of 1:6. Combination estrogen and progesterone oral contraceptive medications have been associated with erythema nodosum for decades (Schwartz & Nervi, 2007). 

Epidemiology

Time Course

Clinical Presentation with Classic S&S

Mechanism of Disease Process

Define: Vitiligo causes the skin to lose its natural color. Patches of lighter skin appear. Some people develop a few patches, while others lose much more skin color.

Demographics: Occurs at any age and affects all races and both sexes equally

Risk Factors: Family history of vitiligo or an autoimmune disease especially Hashimoto’s or alopecia

Exposures: None

Pattern of Symptoms: There is no way to tell if vitiligo will spread. For some people, the white patches do not spread. But often the white patches will spread to other areas of the body. For some people, vitiligo spreads slowly, over many years. For other people, spreading happens quickly. Some people have reported more white patches after physical or emotional stress (National Institute of Arthritis and Musculoskeletal and Skin Disease [NIAMS], 2014).

Symptoms: White patches on the skin that may itch or feel painful

Signs: Depigmentation of the skin commonly in areas where the skin is exposed to the sun, but can appear anywhere on the body. Hair may turn gray earlier and those with dark skin may notice a loss of color in their mouths.

Must Have Features: Biopsy of the skin showing complete absence of melanocytes

Rejecting Features: Visual changes, white patches that go away over time

Diagnostics: Microscopic examination of the skin with biopsy shows total loss of epidermal pigmentation (NIAMS, 2014).

Pathophysiology: Vitiligo is a multifactorial polygenic disorder with a complex pathogenesis. It is related to both genetic and non-genetic factors. Although several theories have been propositioned about the pathogenesis of vitiligo, the exact cause remains unknown. Generally agreed upon principles are an absence of functional melanocytes in vitiligo skin and a loss of melanocytes, due to their destruction. However, the destruction is most likely a slow process resulting in a progressive decrease of melanocytes. Theories regarding destruction of melanocytes include autoimmune mechanisms, cytotoxic mechanisms, intrinsic melanocyte defects, oxidant-antioxidant mechanisms, and neural mechanisms (NIAMS, 2014).

Known Derangements: Family and twin studies have shown that inheritance is complex and likely involves both genetic and environmental factors. It is thought that genetic factors may impact the age of onset of vitiligo. The inheritance of vitiligo may include genes associated with the biosynthesis of melanin, a response to oxidative stress, and regulation of autoimmunity (NIAMS, 2014).

Epidemiology

Time Course

Clinical Presentation with Classic S&S

Mechanism of Disease Process

Define: Rosacea is a common skin condition that causes redness and visible blood vessels in your face. It may also produce small, red, pus-filled bumps (American Academy of Dermatology, 2017).

Demographics: Between the age of 30 and 50, Celtic or Scandinavian ancestry, women> men

Risk Factors: Fair skinned, blonde hair and blue eyes, family history of rosacea, lots of acne, between the age of 30 and 50, and smoking

Exposures: Hereditary and smoke cigarettes

Pattern of Symptoms: Chronic and worsening

Symptoms: Facial redness, swollen red bumps, skin may feel hot and tender, dry skin, eye dryness or irritation, and enlarged nose.

Signs: Rosacea usually causes a persistent redness in the central part of your face. Small blood vessels on your nose and cheeks often swell and become visible. Many people who have rosacea also develop pimples on their face that resemble acne. These bumps sometimes contain pus (American Academy of Dermatology, 2017).

Must Have Features: Rosacea is defined by persistent erythema of the central portion of the face lasting for at least 3 months. Supporting criteria include flushing, papules, and pustules (American Academy of Dermatology, 2017).

Rejecting Features: Photosensitivity, acne alone, facial flushing that goes away.

Diagnostics: Examination of the skin and eyes

Pathophysiology: The exact pathophysiology of rosacea is unknown. There is not a single physiopathological model. 

The pathophysiology of rosacea appears to be complex, as virtually all cutaneous cells, including immune cells, seem to have roles (American Academy of Dermatology, 2017).

Known Derangements: The higher incidence of rosacea in those of Celtic or Northern European descent also suggests a possible genetic component. Still, several genomic studies have failed to pinpoint a causative gene.

The innate immune system seems to be disrupted in patients who have rosacea. As discussed earlier, serine protease levels are elevated in those with rosacea, and this may result in epidermal barrier dysfunction. A stinging or burning sensation results when a sensory irritant, such as lactic acid for example, easily penetrates the skin through a disruption or abnormality in the epidermal barrier (American Academy of Dermatology, 2017).