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Psoriasis

Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by patches of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small localized patches to complete body coverage. Injury to the skin can trigger psoriatic skin changes at that spot, which is known as the Koebner phenomenon.

The five main types of psoriasis are plaque, guttate, inverse, pustular, and erythrodermic. Plaque psoriasis, also known as psoriasis vulgaris, makes up about 90% of cases. It typically presents as red patches with white scales on top. Areas of the body most commonly affected are the back of the forearms, shins, navel area, and scalp. Guttate psoriasis has drop-shaped lesions. Pustular psoriasis presents as small, noninfectious, pus-filled blisters. Inverse psoriasis forms red patches in skin folds. Erythrodermic psoriasis occurs when the rash becomes very widespread, and can develop from any of the other types. Fingernails and toenails are affected in most people with psoriasis at some point in time. This may include pits in the nails or changes in nail color.

Psoriasis is generally thought to be a genetic disease that is triggered by environmental factors. If one twin has psoriasis, the other twin is three times more likely to be affected if the twins are identical than if they are nonidentical. This suggests that genetic factors predispose to psoriasis. Symptoms often worsen during winter and with certain medications, such as beta blockers or NSAIDs. Infections and psychological stress can also play a role. The underlying mechanism involves the immune system reacting to skin cells. Diagnosis is typically based on the signs and symptoms.

There is no known cure for psoriasis, but various treatments can help control the symptoms. These treatments include steroid creams, vitamin D3 cream, ultraviolet light, immunosuppressive drugs, such as methotrexate, and biologic therapies targeting specific immunologic pathways. About 75% of skin involvement improves with creams alone. The disease affects 2–4% of the population. Men and women are affected with equal frequency. The disease may begin at any age, but typically starts in adulthood. Psoriasis is associated with an increased risk of psoriatic arthritis, lymphomas, cardiovascular disease, Crohn's disease, and depression. Psoriatic arthritis affects up to 30% of individuals with psoriasis.

The word "psoriasis" is from Greek ψωρίασις, meaning "itching condition" or "being itchy" from psora, "itch", and -iasis, "action, condition".

Plaque psoriasis
Psoriasis vulgaris (also known as chronic stationary psoriasis or plaque-like psoriasis) is the most common form and affects 85–90% of people with psoriasis. Plaque psoriasis typically appears as raised areas of inflamed skin covered with silvery-white, scaly skin. These areas are called plaques and are most commonly found on the elbows, knees, scalp, and back.

Other forms
Additional types of psoriasis comprise about 10% of cases. They include pustular, inverse, napkin, guttate, oral, and seborrheic-like forms.

Pustular psoriasis
Pustular psoriasis appears as raised bumps filled with noninfectious pus (pustules). The skin under and surrounding the pustules is red and tender. Pustular psoriasis can either be localized or more widespread throughout the body. Two types of localized pustular psoriasis include psoriasis pustulosa palmoplantaris and acrodermatitis continua of Hallopeau; both forms are localized to the hands and feet.

Inverse psoriasis
Inverse psoriasis (also known as flexural psoriasis) appears as smooth, inflamed patches of skin. The patches frequently affect skin folds, particularly around the genitals (between the thigh and groin), the armpits, in the skin folds of an overweight abdomen (known as panniculus), between the buttocks in the intergluteal cleft, and under the breasts in the inframammary fold. Heat, trauma, and infection are thought to play a role in the development of this atypical form of psoriasis.

Napkin psoriasis
Napkin psoriasis is a subtype of psoriasis common in infants under the age of two and is characterized by red papules with silver scale in the diaper area that may extend to the torso or limbs. Napkin psoriasis is often misdiagnosed as napkin dermatitis (diaper rash). It typically improves as children age and may later presents in more common forms as plaque psoriasis or inverse psoriasis.

Guttate psoriasis
Guttate psoriasis is an inflammatory condition characterized by numerous small, scaly, red or pink, droplet-like lesions (papules). These numerous papules appear over large areas of the body, primarily the trunk, limbs, and scalp, but typically spares the palms and soles. Guttate psoriasis is often triggered by a streptococcal infection (oropharyngeal or perianal) and typically occurs 1–3 weeks post-infection. Guttate psoriasis is most commonly seen in children and young adults and diagnosis is typically made based on history and clinical exam findings. Skin biopsy can also be performed which typically shows a psoriasiform reaction pattern characterized by epidermal hyperplasia with elongation of the rete ridges.

There is no firm evidence regarding best management for guttate psoriasis; however, first line therapy for mild guttate psoriasis typically includes topical corticosteroids. Phototherapy can be used for moderate or severe guttate psoriasis. Biologic treatments have not been well studied in the treatment of guttate psoriasis.

Guttate psoriasis has a better prognosis than plaque psoriasis and typically resolves within 1–3 weeks; however, up to 40% of patients with guttate psoriasis eventually convert to plaque psoriasis.

Erythrodermic psoriasis
Psoriatic erythroderma (erythrodermic psoriasis) involves widespread inflammation and exfoliation of the skin over most of the body surface, often involving greater than 90% of the body surface area. It may be accompanied by severe dryness, itching, swelling, and pain. It can develop from any type of psoriasis. It is often the result of an exacerbation of unstable plaque psoriasis, particularly following the abrupt withdrawal of systemic glucocorticoids. This form of psoriasis can be fatal as the extreme inflammation and exfoliation disrupt the body's ability to regulate temperature and perform barrier functions.

Mouth
Psoriasis in the mouth is very rare, in contrast to lichen planus, another common papulosquamous disorder that commonly involves both the skin and mouth. When psoriasis involves the oral mucosa (the lining of the mouth), it may be asymptomatic, but it may appear as white or grey-yellow plaques. Fissured tongue is the most common finding in those with oral psoriasis and has been reported to occur in 6.5–20% of people with psoriasis affecting the skin. The microscopic appearance of oral mucosa affected by geographic tongue (migratory stomatitis) is very similar to the appearance of psoriasis. A recent study just found an association between the two conditions, and it suggests that geographic tongue might be a predictor to psoriasis.

Seborrheic-like psoriasis
Seborrheic-like psoriasis is a common form of psoriasis with clinical aspects of psoriasis and seborrheic dermatitis, and it may be difficult to distinguish from the latter. This form of psoriasis typically manifests as red plaques with greasy scales in areas of higher sebum production such as the scalp, forehead, skin folds next to the nose, the skin surrounding the mouth, skin on the chest above the sternum, and in skin folds.

Psoriatic arthritis
Psoriatic arthritis is a form of chronic inflammatory arthritis that has a highly variable clinical presentation and frequently occurs in association with skin and nail psoriasis. It typically involves painful inflammation of the joints and surrounding connective tissue, and can occur in any joint, but most commonly affects the joints of the fingers and toes. This can result in a sausage-shaped swelling of the fingers and toes known as dactylitis. Psoriatic arthritis can also affect the hips, knees, spine (spondylitis), and sacroiliac joint (sacroiliitis). About 30% of individuals with psoriasis will develop psoriatic arthritis. Skin manifestations of psoriasis tend to occur before arthritic manifestations in about 75% of cases.

Nail changes
Psoriasis can affect the nails and produces a variety of changes in the appearance of fingers and toenails. Nail psoriasis occurs in 40–45% of people with psoriasis affecting the skin, and has a lifetime incidence of 80–90% in those with psoriatic arthritis. These changes include pitting of the nails (pinhead-sized depressions in the nail is seen in 70% with nail psoriasis), whitening of the nail, small areas of bleeding from capillaries under the nail, yellow-reddish discoloration of the nails known as the oil drop or salmon spots, dryness, thickening of the skin under the nail (subungual hyperkeratosis), loosening and separation of the nail (onycholysis), and crumbling of the nail.

Medical signs
In addition to the appearance and distribution of the rash, specific medical signs may be used by medical practitioners to assist with diagnosis. These may include Auspitz's sign (pinpoint bleeding when scale is removed), Koebner phenomenon (psoriatic skin lesions induced by trauma to the skin), and itching and pain localized to papules and plaques.

Causes
The cause of psoriasis is not fully understood. Genetics, seasonal changes, skin damage, climate, immunocompromised state, specific infections, and the use of some medications have been connected with different types of psoriasis.

Genetics
Around one-third of people with psoriasis report a family history of the disease, and researchers have identified genetic loci associated with the condition. Identical twin studies suggest a 70% chance of a twin developing psoriasis if the other twin has the disorder. The risk is around 20% for fraternal twins. These findings suggest both a genetic susceptibility and an environmental response in developing psoriasis.

Psoriasis has a strong hereditary component, and many genes are associated with it, but how those genes work together is unclear. Most of the identified genes relate to the immune system, particularly the major histocompatibility complex (MHC) and T cells. Genetic studies are valuable due to their ability to identify molecular mechanisms and pathways for further study and potential medication targets.

Classic genome-wide linkage analysis has identified nine loci on different chromosomes associated with psoriasis. They are called psoriasis susceptibility 1 through 9 (PSORS1 through PSORS9). Within those loci are genes on pathways that lead to inflammation. Certain variations (mutations) of those genes are commonly found in psoriasis. Genome-wide association scans have identified other genes that are altered to characteristic variants in psoriasis. Some of these genes express inflammatory signal proteins, which affect cells in the immune system that are also involved in psoriasis. Some of these genes are also involved in other autoimmune diseases.

The major determinant is PSORS1, which probably accounts for 35–50% of psoriasis heritability. It controls genes that affect the immune system or encode skin proteins that are overabundant with psoriasis. PSORS1 is located on chromosome 6 in the MHC, which controls important immune functions. Three genes in the PSORS1 locus have a strong association with psoriasis vulgaris: HLA-C variant HLA-Cw6, which encodes an MHC class I protein; CCHCR1, variant WWC, which encodes a coiled coil protein overexpressed in psoriatic epidermis; and CDSN, variant allele 5, which encodes corneodesmosin, a protein expressed in the granular and cornified layers of the epidermis and upregulated in psoriasis.

Two major immune system genes under investigation are interleukin-12 subunit beta (IL12B) on chromosome 5q, which expresses interleukin-12B; and IL23R on chromosome 1p, which expresses the interleukin-23 receptor, and is involved in T cell differentiation. Interleukin-23 receptor and IL12B have both been strongly linked with psoriasis. T cells are involved in the inflammatory process that leads to psoriasis. These genes are on the pathway that upregulate tumor necrosis factor-α and nuclear factor κB, two genes involved in inflammation. The first gene directly linked to psoriasis was identified as the CARD14 gene located in the PSORS2 locus. A rare mutation in the gene encoding for the CARD14-regulated protein plus an environmental trigger was enough to cause plaque psoriasis (the most common form of psoriasis).

Lifestyle
Conditions reported as worsening the disease include chronic infections, stress, and changes in season and climate. Others factors that might worsen the condition include hot water, scratching psoriasis skin lesions, skin dryness, excessive alcohol consumption, cigarette smoking, and obesity. The effects of stopping cigarette smoking or alcohol misuse have yet to be studied as of 2019.

HIV
The rate of psoriasis in human immunodeficiency virus-positive (HIV) individuals is comparable to that of HIV-negative individuals, but psoriasis tends to be more severe in people infected with HIV. A much higher rate of psoriatic arthritis occurs in HIV-positive individuals with psoriasis than in those without the infection. The immune response in those infected with HIV is typically characterized by cellular signals from Th2 subset of CD4+ helper T cells, whereas the immune response in psoriasis vulgaris is characterized by a pattern of cellular signals typical of Th1 subset of CD4+ helper T cells and Th17 helper T cells. The diminished CD4+-T cell presence is thought to cause an overactivation of CD8+-T cells, which are responsible for the exacerbation of psoriasis in HIV-positive people. Psoriasis in those with HIV/AIDS is often severe and may be untreatable with conventional therapy. In those with long-term, well-controlled psoriasis, new HIV infection can trigger a severe flare-up of psoriasis and/or psoriatic arthritis.

Microbes
Psoriasis has been described as occurring after strep throat, and may be worsened by skin or gut colonization with Staphylococcus aureus, Malassezia spp., and Candida albicans. Guttate psoriasis often affects children and adolescents and can be triggered by a recent group A streptococcal infection (tonsillitis or pharyngitis).

Medications
Drug-induced psoriasis may occur with beta blockers, lithium, antimalarial medications, nonsteroidal anti-inflammatory drugs, terbinafine, calcium channel blockers, captopril, glyburide, granulocyte colony-stimulating factor, interleukins, interferons, lipid-lowering medications, and paradoxically TNF inhibitors such as infliximab or adalimumab. Withdrawal of corticosteroids (topical steroid cream) can aggravate psoriasis due to the rebound effect.

Pathophysiology
Psoriasis is characterized by an abnormally excessive and rapid growth of the epidermal layer of the skin. Abnormal production of skin cells (especially during wound repair) and an overabundance of skin cells result from the sequence of pathological events in psoriasis. The sequence of pathological events in psoriasis is thought to start with an initiation phase in which an event (skin trauma, infection, or drugs) leads to activation of the immune system and then the maintenance phase consisting of chronic progression of the disease. Skin cells are replaced every 3–5 days in psoriasis rather than the usual 28–30 days. These changes are believed to stem from the premature maturation of keratinocytes induced by an inflammatory cascade in the dermis involving dendritic cells, macrophages, and T cells (three subtypes of white blood cells). These immune cells move from the dermis to the epidermis and secrete inflammatory chemical signals (cytokines) such as interleukin-36γ, tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-22. These secreted inflammatory signals are believed to stimulate keratinocytes to proliferate. One hypothesis is that psoriasis involves a defect in regulatory T cells, and in the regulatory cytokine interleukin-10. The inflammatory cytokines found in psoriatic nails and joints (in the case of psoriatic arthritis) are similar to those of psoriatic skin lesions, suggesting a common inflammatory mechanism.

Gene mutations of proteins involved in the skin's ability to function as a barrier have been identified as markers of susceptibility for the development of psoriasis.

Deoxyribonucleic acid (DNA) released from dying cells acts as an inflammatory stimulus in psoriasis and stimulates the receptors on certain dendritic cells, which in turn produce the cytokine interferon-α. In response to these chemical messages from dendritic cells and T cells, keratinocytes also secrete cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor-α, which signal downstream inflammatory cells to arrive and stimulate additional inflammation.

Dendritic cells bridge the innate immune system and adaptive immune system. They are increased in psoriatic lesions and induce the proliferation of T cells and type 1 helper T cells (Th1). Targeted immunotherapy, as well as psoralen and ultraviolet A (PUVA) therapy, can reduce the number of dendritic cells and favors a TH2 cell cytokine secretion pattern over a Th1/Th17 cell cytokine profile. Psoriatic T cells move from the dermis into the epidermis and secrete interferon-γ and interleukin-17. Interleukin-23 is known to induce the production of interleukin-17 and interleukin-22. Interleukin-22 works in combination with interleukin-17 to induce keratinocytes to secrete neutrophil-attracting cytokines.

Diagnosis
A diagnosis of psoriasis is usually based on the appearance of the skin. Skin characteristics typical for psoriasis are scaly, erythematous plaques, papules, or patches of skin that may be painful and itch. No special blood tests or diagnostic procedures are usually required to make the diagnosis.

The differential diagnosis of psoriasis includes dermatological conditions similar in appearance such as discoid eczema, seborrheic eczema, pityriasis rosea (may be confused with guttate psoriasis), nail fungus (may be confused with nail psoriasis) or cutaneous T cell lymphoma (50% of individuals with this cancer are initially misdiagnosed with psoriasis). Dermatologic manifestations of systemic illnesses such as the rash of secondary syphilis may also be confused with psoriasis.

If the clinical diagnosis is uncertain, a skin biopsy or scraping may be performed to rule out other disorders and to confirm the diagnosis. Skin from a biopsy shows clubbed epidermal projections that interdigitate with dermis on microscopy. Epidermal thickening is another characteristic histologic finding of psoriasis lesions. The stratum granulosum layer of the epidermis is often missing or significantly decreased in psoriatic lesions; the skin cells from the most superficial layer of skin are also abnormal as they never fully mature. Unlike their mature counterparts, these superficial cells keep their nuclei. Inflammatory infiltrates can typically be seen on microscopy when examining skin tissue or joint tissue affected by psoriasis. Epidermal skin tissue affected by psoriatic inflammation often has many CD8+ T cells, while a predominance of CD4+ T cells makes up the inflammatory infiltrates of the dermal layer of skin and the joints.

Morphological
Psoriasis is classified as a papulosquamous disorder and is most commonly subdivided into different categories based on histological characteristics. Variants include plaque, pustular, guttate, and flexural psoriasis. Each form has a dedicated ICD-10 code. Psoriasis can also be classified into nonpustular and pustular types.

Pathogenetic
Another classification scheme considers genetic and demographic factors. Type 1 has a positive family history, starts before the age of 40, and is associated with the human leukocyte antigen, HLA-Cw6. Conversely, type 2 does not show a family history, presents after age 40, and is not associated with HLA-Cw6. Type 1 accounts for about 75% of persons with psoriasis.

The classification of psoriasis as an autoimmune disease has sparked considerable debate. Researchers have proposed differing descriptions of psoriasis and psoriatic arthritis; some authors have classified them as autoimmune diseases while others have classified them as distinct from autoimmune diseases and referred to them as immune-mediated inflammatory diseases.

Severity
No consensus exists about how to classify the severity of psoriasis. Mild psoriasis has been defined as a percentage of body surface area (BSA)≤10, a Psoriasis Area and Severity Index (PASI) score ≤10, and a Dermatology Life Quality Index (DLQI) score ≤10. Moderate to severe psoriasis was defined by the same group as BSA >10 or PASI score >10 and a DLQI score >10.

The DLQI is a 10-question tool used to measure the impact of several dermatologic diseases on daily functioning. The DLQI score ranges from 0 (minimal impairment) to 30 (maximal impairment) and is calculated with each answer being assigned 0–3 points with higher scores indicating greater social or occupational impairment.

The PASI is the most widely used measurement tool for psoriasis. It assesses the severity of lesions and the area affected and combines these two factors into a single score from 0 (no disease) to 72 (maximal disease). Nevertheless, the PASI can be too unwieldy to use outside of research settings, which has led to attempts to simplify the index for clinical use.

Co-morbidities
Psoriasis is not just a skin disease. The symptoms of psoriasis can sometimes go beyond the skin and can have a negative impact on the quality of life of the affected individuals. Additionally, the co-morbidities increase the treatment and financial burden of psoriasis and should be considered when managing this condition.

Cardiovascular complications
There is 2.2 times increased risk of cardiovascular complications in people with psoriasis. Also, people with psoriasis are more susceptible to myocardial infarction (heart attack) and stroke. It has been speculated that there is systemic inflammation in psoriasis, which drives “psoriatic march” and can cause other inflammatory complications including cardiovascular complications. A study used fluorodeoxyglucose F-18 positron emission tomography computed tomography (FDG PET/CT) to measure aortic vascular inflammation in psoriasis patients, and found increased coronary artery disease indices, including total plaque burden, luminal stenosis, and high-risk plaques in people with psoriasis. Similarly, it was found that there is 11% reduction in aortic vascular inflammation when there is 75% reduction in PASI score.

Depression
Depression or depressive symptoms are present in 28–55% of people with psoriasis. People with psoriasis are often stigmatized due to visible disfigurement of the skin. Social stigmatization is a risk factor for depression, however, other immune system factors may also be related to this observed increased incidence of depression in people with psoriasis. There is some evidence that increased inflammatory signals in the body could also contribute to depression in people with chronic inflammatory diseases, including psoriasis.

Type 2 diabetes
People with psoriasis are at increased risk of developing type 2 diabetes (~1.5 odds ratio). A genome-wide based genetic study found that psoriasis and type 2 diabetes share four loci, namely, ACTR2, ERLIN1, TRMT112, and BECN1, which are connected via inflammatory NF-κB pathway.

Management
While no cure is available for psoriasis, many treatment options exist. Topical agents are typically used for mild disease, phototherapy for moderate disease, and systemic agents for severe disease. There is no evidence to support the effectiveness of conventional topical and systemic drugs, biological therapy, or phototherapy for acute guttate psoriasis or an acute guttate flare of chronic psoriasis.

Topical agents
Topical corticosteroid preparations are the most effective agents when used continuously for eight weeks; retinoids and coal tar were found to be of limited benefit and may be no better than placebo. Very potent topical corticosteroids may be helpful in some cases, however, it is suggested to only use them for four weeks at a time and only if other less potent topical treatment options are not working.

Vitamin D analogues such as paricalcitol are superior to placebo. Combination therapy with vitamin D and a corticosteroid are superior to either treatment alone and vitamin D is superior to coal tar for chronic plaque psoriasis.

For psoriasis of the scalp, a 2016 review found dual therapy (vitamin D analogues and topical corticosteroids) or corticosteroid monotherapy to be more effective and safer than topical vitamin D analogues alone. Due to their similar safety profiles and minimal benefit of dual therapy over monotherapy, corticosteroid monotherapy appears to be an acceptable treatment for short-term treatment.

Moisturizers and emollients such as mineral oil, petroleum jelly, calcipotriol, and decubal (an oil-in-water emollient) were found to increase the clearance of psoriatic plaques. Some emollients have been shown to be even more effective at clearing psoriatic plaques when combined with phototherapy. Certain emollients, though, have no impact on psoriasis plaque clearance or may even decrease the clearance achieved with phototherapy, e.g. the emollient salicylic acid is structurally similar to para-aminobenzoic acid, commonly found in sunscreen, and is known to interfere with phototherapy in psoriasis. Coconut oil, when used as an emollient in psoriasis, has been found to decrease plaque clearance with phototherapy. Medicated creams and ointments applied directly to psoriatic plaques can help reduce inflammation, remove built-up scale, reduce skin turnover, and clear affected skin of plaques. Ointment and creams containing coal tar, dithranol, corticosteroids (i.e. desoximetasone), fluocinonide, vitamin D3 analogues (for example, calcipotriol), and retinoids are routinely used. (The use of the finger tip unit may be helpful in guiding how much topical treatment to use.)

Vitamin D analogues may be useful with steroids; steroids alone have a higher rate of side effects. Vitamin D analogues may allow less steroids to be used.

Another topical therapy used to treat psoriasis is a form of balneotherapy, which involves daily baths in the Dead Sea. This is usually done for four weeks with the benefit attributed to sun exposure and specifically UVB light. This is cost-effective and it has been propagated as an effective way to treat psoriasis without medication. Decreases of PASI scores greater than 75% and remission for several months have commonly been observed. Side effects may be mild such as itchiness, folliculitis, sunburn, poikiloderma, and a theoretical risk of nonmelanoma cancer or melanoma has been suggested. Some studies indicate no increased risk of melanoma in the long term. Data are inconclusive with respect to nonmelanoma skin cancer risk, but support the idea that the therapy is associated with an increased risk of benign forms of sun-induced skin damage such as, but not limited to, actinic elastosis or liver spots. Dead Sea balneotherapy is also effective for psoriatic arthritis. Tentative evidence indicates that balneophototherapy, a combination of salt bathes and exposure to ultraviolet B-light (UVB), in chronic plaque psoriasis is better than UVB alone. Glycerin is also an effective treatment for Psoriasis.

UV phototherapy
Phototherapy in the form of sunlight has long been used for psoriasis. UVB wavelengths of 311–313 nanometers are most common. These lamps have been developed for this treatment. The exposure time should be controlled to avoid overexposure and burning of the skin. The UVB lamps should have a timer that turns off the lamp when the time ends. The dose is increased in every treatment to let the skin get used to the light. Increased rates of cancer from treatment appear to be small. Narrowband UVB therapy has been demonstrated to have similar efficacy to psoralen and ultraviolet A phototherapy (PUVA). A 2013 meta-analysis found no difference in efficacy between NB-UVB and PUVA in the treatment of psoriasis, but NB-UVB is usually more convenient.

One of the problems with clinical phototherapy is the difficulty many people have gaining access to a facility. Indoor tanning resources are almost ubiquitous today and could be considered as a means for people to get UV exposure when dermatologist-provided phototherapy is not available. Indoor tanning is already used by many people as a treatment for psoriasis; one indoor facility reported that 50% of its clients were using the center for psoriasis treatment; another reported 36% were doing the same thing. However, a concern with the use of commercial tanning is that tanning beds that primarily emit UVA might not effectively treat psoriasis. One study found that plaque psoriasis is responsive to erythemogenic doses of either UVA or UVB, as exposure to either can cause dissipation of psoriatic plaques. It does require more energy to reach erythemogenic dosing with UVA.

UV light therapies all have risks; tanning beds are no exception, being listed by the World Health Organization as carcinogens. Exposure to UV light is known to increase the risks of melanoma and squamous cell and basal cell carcinomas; younger people with psoriasis, particularly those under age 35, are at increased risk from melanoma from UV light treatment. A review of studies recommends that people who are susceptible to skin cancers exercise caution when using UV light therapy as a treatment.

A major mechanism of NB-UVB is the induction of DNA damage in the form of pyrimidine dimers. This type of phototherapy is useful in the treatment of psoriasis because the formation of these dimers interferes with the cell cycle and stops it. The interruption of the cell cycle induced by NB-UVB opposes the characteristic rapid division of skin cells seen in psoriasis. The activity of many types of immune cells found in the skin is also effectively suppressed by NB-UVB phototherapy treatments. The most common short-term side effect of this form of phototherapy is redness of the skin; less common side effects of NB-UVB phototherapy are itching and blistering of the treated skin, irritation of the eyes in the form of conjunctival inflammation or inflammation of the cornea, or cold sores due to reactivation of the herpes simplex virus in the skin surrounding the lips. Eye protection is usually given during phototherapy treatments.

PUVA combines the oral or topical administration of psoralen with exposure to ultraviolet A (UVA) light. The mechanism of action of PUVA is unknown, but probably involves activation of psoralen by UVA light, which inhibits the abnormally rapid production of the cells in psoriatic skin. There are multiple mechanisms of action associated with PUVA, including effects on the skin's immune system. PUVA is associated with nausea, headache, fatigue, burning, and itching. Long-term treatment is associated with squamous cell carcinoma (but not with melanoma). A combination therapy for moderate to severe psoriasis using PUVA plus acitretin resulted in benefit, but acitretin use has been associated with birth defects and liver damage.

Systemic agents
Psoriasis resistant to topical treatment and phototherapy may be treated with systemic therapies including medications by mouth or injectable treatments. People undergoing systemic treatment must have regular blood and liver function tests to check for medication toxicities. Pregnancy must be avoided for most of these treatments. The majority of people experience a recurrence of psoriasis after systemic treatment is discontinued.

Non-biologic systemic treatments frequently used for psoriasis include methotrexate, ciclosporin, hydroxycarbamide, fumarates such as dimethyl fumarate, and retinoids. Methotrexate and ciclosporin are medications that suppress the immune system; retinoids are synthetic forms of vitamin A. These agents are also regarded as first-line treatments for psoriatic erythroderma. Oral corticosteroids should not be used as they can severely flare psoriasis upon their discontinuation.

Biologics are manufactured proteins that interrupt the immune process involved in psoriasis. Unlike generalized immunosuppressive medical therapies such as methotrexate, biologics target specific aspects of the immune system contributing to psoriasis. These medications are generally well-tolerated, and limited long-term outcome data have demonstrated biologics to be safe for long-term use in moderate to severe plaque psoriasis. However, due to their immunosuppressive actions, biologics have been associated with a small increase in the risk for infection.

Guidelines regard biologics as third-line treatment for plaque psoriasis following inadequate response to topical treatment, phototherapy, and non-biologic systemic treatments. The safety of biologics during pregnancy has not been assessed. European guidelines recommend avoiding biologics if a pregnancy is planned; anti-TNF therapies such as infliximab are not recommended for use in chronic carriers of the hepatitis B virus or individuals infected with HIV.

Several monoclonal antibodies target cytokines, the molecules that cells use to send inflammatory signals to each other. TNF-α is one of the main executor inflammatory cytokines. Four monoclonal antibodies (MAbs) (infliximab, adalimumab, golimumab, and certolizumab pegol) and one recombinant TNF-α decoy receptor, etanercept, have been developed to inhibit TNF-α signaling. Additional monoclonal antibodies, such as ixekizumab, have been developed against pro-inflammatory cytokines and inhibit the inflammatory pathway at a different point than the anti-TNF-α antibodies. IL-12 and IL-23 share a common domain, p40, which is the target of the FDA-approved ustekinumab. In 2017 the US FDA approved guselkumab for plaque psoriasis. There have been few studies of the efficacy of anti-TNF medications for psoriasis in children. One randomized control study suggested that 12 weeks of etanercept treatment reduced the extent of psoriasis in children with no lasting adverse effects.

Two medications that target T cells are efalizumab and alefacept. Efalizumab is a monoclonal antibody that specifically targets the CD11a subunit of LFA-1. It also blocks the adhesion molecules on the endothelial cells that line blood vessels, which attract T cells. Efalizumab was voluntarily withdrawn from the European market in February 2009, and from the U.S. market in June 2009, by the manufacturer due to the medication's association with cases of progressive multifocal leukoencephalopathy. Alefacept also blocks the molecules that dendritic cells use to communicate with T cells and even causes natural killer cells to kill T cells as a way of controlling inflammation. Apremilast may also be used.

Individuals with psoriasis may develop neutralizing antibodies against monoclonal antibodies. Neutralization occurs when an antidrug antibody prevents a monoclonal antibody such as infliximab from binding antigen in a laboratory test. Specifically, neutralization occurs when the anti-drug antibody binds to infliximab's antigen binding site instead of TNF-α. When infliximab no longer binds tumor necrosis factor alpha, it no longer decreases inflammation, and psoriasis may worsen. Neutralizing antibodies have not been reported against etanercept, a biologic medication that is a fusion protein composed of two TNF-α receptors. The lack of neutralizing antibodies against etanercept is probably secondary to the innate presence of the TNF-α receptor, and the development of immune tolerance.

There is strong evidence to indicate that infliximab, bimekizumab, ixekizumab, and risankizumab are the most effective biologics for treating moderate to severe cases of psoriasis. There is also some evidence to support use of secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab. In general, anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha biologics were found to be more effective than traditional systemic treatments. The immunologic pathways of psoriasis involve Th9, Th17, Th1 lymphocytes, and IL-22. The aforementioned biologic agents hinder different aspects of these pathways.

Another set of treatments for moderate to severe psoriasis are fumaric acid esters (FAE), which may be similar in effectiveness to methotrexate.

Apremilast (Otezla, Celgene) is an oral small-molecule inhibitor of the enzyme phosphodiesterase 4, which plays an important role in chronic inflammation associated with psoriasis.

It has been theorized that antistreptococcal medications may improve guttate and chronic plaque psoriasis; however, the limited studies do not show that antibiotics are effective.

Surgery
Limited evidence suggests removal of the tonsils may benefit people with chronic plaque psoriasis, guttate psoriasis, and palmoplantar pustulosis.

Diet
Uncontrolled studies have suggested that individuals with psoriasis or psoriatic arthritis may benefit from a diet supplemented with fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A low-calorie diet appears to reduce the severity of psoriasis. Diet recommendations include consumption of cold water fish (preferably wild fish, not farmed) such as salmon, herring, and mackerel; extra virgin olive oil; legumes; vegetables; fruits; and whole grains; and avoid consumption of alcohol, red meat, and dairy products (due to their saturated fat). The effect of consumption of caffeine (including coffee, black tea, mate, and dark chocolate) remains to be determined.

Many patients report improvements after consuming less tobacco, caffeine, sugar, nightshades (tomatoes, eggplant, peppers, paprika and white potatoes) and taking probiotics and oral Vitamin D.

There is a higher rate of celiac disease among people with psoriasis. When adopting a gluten-free diet, disease severity generally decreases in people with celiac disease and those with anti-gliadin antibodies.

Prognosis
Most people with psoriasis experience nothing more than mild skin lesions that can be treated effectively with topical therapies. Depending on the severity and location of outbreaks, people may experience significant physical discomfort and some disability, affecting the person's quality of life. Itching and pain can interfere with basic functions, such as self-care and sleep. Participation in sporting activities, certain occupations, and caring for family members can become difficult activities for those with plaques located on their hands and feet. Plaques on the scalp can be particularly embarrassing, as flaky plaque in the hair can be mistaken for dandruff. Individuals with psoriasis may feel self-conscious about their appearance and have a poor self-image that stems from fear of public rejection and psychosexual concerns. Psoriasis has been associated with low self-esteem and depression is more common among those with the condition. People with psoriasis often feel prejudiced against due to the commonly held incorrect belief that psoriasis is contagious. Psychological distress can lead to significant depression and social isolation; a high rate of thoughts about suicide has been associated with psoriasis. Many tools exist to measure the quality of life of people with psoriasis and other dermatological disorders. Clinical research has indicated individuals often experience a diminished quality of life. Children with psoriasis may encounter bullying.

Several conditions are associated with psoriasis including obesity, cardiovascular, and metabolic disturbances. These occur more frequently in older people. Nearly half of individuals with psoriasis over the age of 65 have at least three comorbidities (concurrent conditions), and two-thirds have at least two comorbidities.

Cardiovascular disease
Psoriasis has been associated with obesity and several other cardiovascular and metabolic disturbances. The number of new cases per year of diabetes is 27% higher in people affected by psoriasis than in those without the condition. Severe psoriasis may be even more strongly associated with the development of diabetes than mild psoriasis. Younger people with psoriasis may also be at increased risk for developing diabetes. Individuals with psoriasis or psoriatic arthritis have a slightly higher risk of heart disease and heart attacks when compared to the general population. Cardiovascular disease risk appeared to be correlated with the severity of psoriasis and its duration. There is no strong evidence to suggest that psoriasis is associated with an increased risk of death from cardiovascular events. Methotrexate may provide a degree of protection for the heart.

The odds of having hypertension are 1.58 times ( i.e. 58%) higher in people with psoriasis than those without the condition; these odds are even higher with severe cases of psoriasis. A similar association was noted in people who have psoriatic arthritis—the odds of having hypertension were found to be 2.07 times ( i.e. 107%) greater when compared to odds of the general population. The link between psoriasis and hypertension is not currently understood. Mechanisms hypothesized to be involved in this relationship include the following: dysregulation of the renin–angiotensin system, elevated levels of endothelin 1 in the blood, and increased oxidative stress. The number of new cases of the heart rhythm abnormality atrial fibrillation is 1.31 times ( i.e. 31%) higher in people with mild psoriasis and 1.63 times ( i.e. 63%) higher in people with severe psoriasis. There may be a slightly increased risk of stroke associated with psoriasis, especially in severe cases. Treating high levels of cholesterol with statins has been associated with decreased psoriasis severity, as measured by PASI score, and has also been associated with improvements in other cardiovascular disease risk factors such as markers of inflammation. These cardioprotective effects are attributed to ability of statins to improve blood lipid profile and because of their anti-inflammatory effects. Statin use in those with psoriasis and hyperlipidemia was associated with decreased levels of high-sensitivity C-reactive protein and TNFα as well as decreased activity of the immune protein LFA-1. Compared to individuals without psoriasis, those affected by psoriasis are more likely to satisfy the criteria for metabolic syndrome.

Other diseases
The rates of Crohn disease and ulcerative colitis are increased when compared with the general population, by a factor of 3.8 and 7.5 respectively. People with psoriasis also have a higher risk of celiac disease. Few studies have evaluated the association of multiple sclerosis with psoriasis, and the relationship has been questioned. Psoriasis has been associated with a 16% increase in overall relative risk for non-skin cancer, thought to be attributed to systemic therapy, particularly methotrexate. People treated with long term systemic therapy for psoriasis have a 52% increased risk cancers of the lung and bronchus, a 205% increase in the risk of developing cancers of the upper gastrointestinal tract, a 31% increase in the risk of developing cancers of the urinary tract, a 90% increase in the risk of developing liver cancer, and a 46% increase in the risk of developing pancreatic cancer. The risk for development of non-melanoma skin cancers is also increased. Psoriasis increases the risk of developing squamous cell carcinoma of the skin by 431% and increases the risk of basal cell carcinoma by 100%. There is no increased risk of melanoma associated with psoriasis. People with psoriasis have a higher risk of developing cancer.

Epidemiology
Psoriasis is estimated to affect 2–4% of the population of the western world. The rate of psoriasis varies according to age, region and ethnicity; a combination of environmental and genetic factors is thought to be responsible for these differences. Psoriasis is about five times more common in people of European descent than in people of Asian descent, more common in countries farther from the equator, relatively uncommon in African Americans, and extremely uncommon in Native Americans. Psoriasis has been estimated to affect about 6.7   million Americans.

Psoriasis can occur at any age, although it is more frequent in adults and commonly appears for the first time between the ages of 15 and 25 years. Approximately one third of people with psoriasis report being diagnosed before age 20. Psoriasis affects both sexes equally.

People with inflammatory bowel disease such as Crohn disease or ulcerative colitis are at an increased risk of developing psoriasis.

History
Scholars believe psoriasis to have been included among the various skin conditions called tzaraath (translated as leprosy) in the Hebrew Bible. The person was deemed "impure" (see tumah and taharah) during their affected phase and is ultimately treated by the kohen. However, it is more likely that this confusion arose from the use of the same Greek term for both conditions. The Greeks used the term lepra (λέπρα) for scaly skin conditions. They used the term psora (ψώρα) to describe itchy skin conditions. It became known as Willan's lepra in the late 18th century when English dermatologists Robert Willan and Thomas Bateman differentiated it from other skin diseases. Leprosy, they said, is distinguished by the regular, circular form of patches, while psoriasis is always irregular. Willan identified two categories: leprosa graecorum and psora leprosa.

Psoriasis is thought to have first been described in Ancient Rome by Cornelius Celsus. The British dermatologist Thomas Bateman described a possible link between psoriasis and arthritic symptoms in 1813. Admiral William Halsey missed out on the Battle of Midway because he contracted psoriasis while out at sea in the early months of American participation of World War II. Admiral Chester Nimitz medically ordered Halsey to recover at a hospital in Hawaii.

The history of psoriasis is littered with treatments of dubious effectiveness and high toxicity. In the 18th and 19th centuries, Fowler's solution, which contains a poisonous and carcinogenic arsenic compound, was used by dermatologists as a treatment for psoriasis. Mercury was also used for psoriasis treatment during this time period. Sulfur, iodine, and phenol were also commonly used treatments for psoriasis during this era when it was incorrectly believed that psoriasis was an infectious disease. Coal tars were widely used with ultraviolet light irradiation as a topical treatment approach in the early 1900s. During the same time period, psoriatic arthritis cases were treated with intravenously administered gold preparations in the same manner as rheumatoid arthritis.

Society and culture
The International Federation of Psoriasis Associations (IFPA) is the global umbrella organization for national and regional psoriasis associations and also gathers the leading experts in psoriasis and psoriatic arthritis research for scientific conferences every three years. The Psoriasis International Network, a program of the Fondation René Touraine, gathers dermatologists, rheumatologists and other caregivers involved in the management of psoriasis. Non-profit organizations like the National Psoriasis Foundation in the United States, the Psoriasis Association in the United Kingdom, and Psoriasis Australia offer advocacy and education about psoriasis in their respective countries.

Cost
The annual cost for treating psoriasis in the United States is estimated as high as $32.5   billion, including $12.2    billion in direct costs. Pharmacy costs are the main source of direct expense, with biologic therapy the most prevalent. These costs increase significantly when co-morbid conditions such as heart disease, hypertension, diabetes, lung disease and psychiatric disorders are factored in. Expenses linked to co-morbidities are estimated at an additional $23,000 per person per year.

Research
The role of insulin resistance in the pathogenesis of psoriasis is under investigation. Preliminary research has suggested that antioxidants such as polyphenols may have beneficial effects on the inflammation characteristic of psoriasis.

Many novel medications being researched during the 2010s target the Th17/IL-23 axis, particularly IL-23p19 inhibitors, as IL-23p19 is present in increased concentrations in psoriasis skin lesions while contributing less to protection against opportunistic infections. Other cytokines such as IL-17 and IL-22 also have been targets for inhibition as they play important roles in the pathogenesis of psoriasis. Another avenue of research has focused on the use of vascular endothelial growth factor inhibitors to treat psoriasis. Oral agents being investigated during the 2010s as alternatives to medications administered by injection include Janus kinase inhibitors, protein kinase C inhibitors, mitogen-activated protein kinase inhibitors, and phosphodiesterase 4 inhibitors, all of which have proven effective in various phase 2 and 3 clinical trials. These agents have potentially severe side-effects due to their immunosuppressive mechanisms.

title: Psoriasis


text:
Sixto Escobar

Sixto Escobar (March 23, 1913 – November 17, 1979) was a Puerto Rican professional boxer. Competing in the bantamweight division, he became Puerto Rico's first world champion.

Escobar was born in Barceloneta and raised in San Juan. There he received his primary education and took interest in boxing. After gathering a record of 21–1–1 as an amateur, Escobar debuted as a professional in 1931 defeating Luis "Kid Dominican" Pérez by knockout. Early in his career, he moved to Venezuela due to the lack of opponents in his division. There he received an opportunity for the Venezuelan Bantamweight championship, but lost by points to Enrique Chaffardet. Subsequently, he moved to New York and began boxing in other states, eventually capturing the Montreal Athletic Commission World Bantamweight Title. In 1936, he defeated Tony Marino to unify this championship with the one recognized by the International Boxing Union, in the process becoming the third Latin American undisputed world boxing champion. After retiring, he worked as a spokesperson for beer companies in New York, before returning to Puerto Rico in the 1960s, where he resided until his death. He received several posthumous recognitions and his name was used in several sports venues and buildings. In 2002, Escobar was inducted into the International Boxing Hall of Fame.

Early life and amateur career
Escobar was born in La Boca in Barrio Palmas Altas, a sector of Barceloneta, Puerto Rico, to Jacinto Escobar and Adela Vargas. Early in his life, he moved to Tras Talleres in Santurce, a subsection of San Juan, Puerto Rico. There he received his elementary and secondary education, up until the seventh grade, when he decided to dedicate himself full-time to his sports career. In Tras Talleres, he began developing an interest in boxing and received instruction in said discipline. Although at this time, boxing was illegal in Puerto Rico; remote places such as a house's backyard or rooftops were used to organize clandestine fights without attracting attention from the local police. In 1928, a Puerto Rican boxer named Ángel "Sotito" Soto moved from New York to a house near the Escobar family's residence and established a gym in his backyard. There he gave boxing classes to Escobar and several other young athletes. After several months of instruction, Soto prepared a boxing card with included three-round fights, in which each round lasted two minutes. In this event, Escobar earned his first victory, defeating a pugilist identified as "Gombar" by knockout in the first round. After this match, Escobar continued fighting in clandestine gyms. He met and was received by Ignacio Peñagaricano, the owner of Victoria Gym. Escobar received his boxing license through Peñagaricano. On February 16, 1927, governor Horace Mann Towner legalized boxing and allowed the establishment of organized boxing matches. Professionals would fight Fridays, Saturdays and Sundays which, were considered the best days of the week, while amateurs could compete the remaining days of the week without limitations. As an amateur, he fought in 23 combats, gathering a record of 21 wins, one loss and a draw. His draw was against Ramón Rodríguez of San Lorenzo and his only loss was in the hands of Pedro Montañez from Cayey, in a fight that took place in March 1930.

Professional career
Escobar turned professional on September 1, 1930, in a fight card organized at the Victory Garden gym in San Juan. In this event, he defeated Luis "Kid Dominican" Pérez, who entered the fight as the Dominican Republic's champion, by knockout in the third round. In Puerto Rico, Escobar fought in 15 contests, before moving to Venezuela after the popularity of professional boxing declined in his home country. This move was motivated by Roberto Andrade, who provided transportation to the country. In Venezuela, he fought in Caracas, competing against José Lugo, Sindulfo Díaz, Rafael "Moralito" Morales, Pica Pica and Simón Chávez among others. On November 11, 1931, Escobar competed against Enrique Chaffardet for the Venezuelan Bantamweight Title, but lost by decision. After 17 fights, he returned to Puerto Rico and competed in five cards. But professional boxing suffered another decline in interest, which forced Escobar to work as an accommodator in baseball games three days of the week, generally on weekends. In the meanwhile, Tony Rojas, a friend of his managers Gustavo Jiménez and Arturo Gigante, convinced them to release Escobar of the contract which bound them. Since Escobar turned professional while he was still legally a minor, his father had to sign the unbinding agreement. After succeeding in this task, Rojas presented Escobar with a steam boat ticket to New York, which covered his food, clothes and hotel expenses. Escobar reached New York in early 1934, intending to "obtain fame and honor" for "[his] motherland", there he was received by Rojas and professional trainer Whitey Bimstein. His first fight in the United States took place at the Valley Arena in Holyoke, Massachusetts on May 7, 1934. In this contest he was paired against Canadian bantamweight titleholder Bobby Leitham, defeating him by technical knockout in the seventh round.

Escobar's manager, Lou Brix and his trainer recognized that Escobar could be close to a championship fight once the incumbent, Panamian Alfonso Teófilo Brown, refused to defend the championship against the first contender, which led to it being stripped by the National Boxing Association (NBA). A rematch was then organized against Leitham. This was an eliminatory card organized by the Montreal Athletic Commission, which was to determine a contender for their vacant Bantamweight World Championship, against first contender Baby Casanova, who attended the card. After scoring three knockdowns in the fourth round, Escobar connected another punch that injured Leitham, after which Leitham's manager surrendered the fight. This marked Leitham's last fight. Following this result, the NBA immediately called for a fight between Escobar and Casanova. By this time he had gained a reputation as a quick and technical boxer, capable of gathering quick knockouts with body punches if confronted by an unprepared opponent. The fight took place on June 26, 1934, and it was organized in Montreal, Quebec, Canada. Escobar scored a knockdown in the third round; the fight concluded in the ninth round when Casanova lost by knockout. With this win, Escobar won the Montreal Athletic Commission World Bantamweight Title, thus becoming the first Puerto Rican to win a world boxing championship title. This had a significant impact on Puerto Rico, where it was constantly discussed by the general public. Songs, decimas and poetry were written about this accomplishment. However, the New York State Athletic Commission (NYSAC) and International Boxing Union (IBU) of France didn't recognize the outcome of this fight, conserving Tony Marino and Brown as their recognized champions.

Undisputed world bantamweight title
On August 8, 1934, he defeated Eugene Hart by points in a non-title match organized in Canada. This was the first time in his career that Escobar completed a 15-round contest. After this event, he stayed in Montreal expecting to fight against the winner of a matchup between Louis Salica and Bobby Quintana, which was scheduled to take place on December of that year. However, Escobar was forced to cancel his plans after suffering a heel injury when he was hit by a car. He spent a month in inactivity while recovering, and in the winter he returned to Puerto Rico. The governor ordered to have all government buildings closed so that public employees could attend a welcoming ceremony. The event, which took place in Old San Juan's dock, was followed by a parade. Upon arriving in Barceloneta, Escobar was recognized as a "predilect son" of that municipality by the city's mayor, which was followed by a week of festivities in his name. Escobar pursued a fight with Brown, but his offers were refused while the Panamanian pugilist promoted a campaign protesting the removal of his recognition as champion, demanding to be reinstated.

On August 7, 1935, Escobar defeated Pete Sanstol—who once held, in 1931, the Canadian Boxing Federation and Montreal Athletic Commission (MAC) world bantamweight titles—by unanimous decision in 12 rounds. However, Escobar still wasn't considered the division's Undisputed Champion because Balthazar Sangchili had defeated Panama Al Brown and was recognized by the IBU. Due to this, Sanstol sent a letter to the NYSAC noting that the fight was of eliminatory nature, even though it was recognized as a titular contest by the NBA and MAC. Wanting to be recognized as such, Escobar pursued a title unification fight against Tony Marino, who had defeated Sangchili by knockout in his previous fight. He won the fight by knockout in the tenth round, receiving the "undisputed world champion" distinction. On November 13, 1935, Escobar became the first Puerto Rican to win a title fight in the first round, defeating "Indian" Quintana by knockout.

This outcome made it possible to organize a fight against Louis Salica, it was the first time that Escobar fought a title fight in Puerto Rico. The card was promoted by Arturo Gigante and Gustavo Jiménez Sicardó. Escobar won the fight by unanimous decision, while Jack Dempsey served as referee. He participated in Mike Jacobs's "Carnival of Champions" on September 23, 1937 and lost the title to Harry Jeffra by unanimous decision. Shortly after, he recovered from this loss and he returned to the gym; he defeated Johnny Defoe in a preparatory contest. On February 20, 1938, Escobar faced Jeffra in a rematch organized at the El Escambrón baseball park in Puerta de Tierra. He won the contest by unanimous decision, scoring three knockdowns. This became an early example of fights that attracted the attention and criticism of boxing analysts, particularly those in New York. On April 2, 1939, Escobar defeated Kayo Morgan before a sold-out crowd of 15,000 at the Estadio Sixto Escobar, which had been inaugurated three years earlier. After this fight, he received The Ring Bantamweight Championship, which was presented by the magazine's editor, Nat Fleischer. Later in 1939, Escobar received a draft notice from the United States Army, ordering him to take a physical exam for possible military service. He and his manager presented the issue to the Puerto Rico Boxing Commission, managing to receive a postponement of two months before surrendering his title. On April 6, 1940, Escobar fought Simón Chávez for ten rounds in what ended as a draw. Escobar then fought some short non-title fights, of which he lost four, all by points. On December 2, 1940, Escobar participated in his last professional fight, losing to a ten-round decision to Harry Jeffra. Throughout his career Escobar avoided being knocked down or out in any fight, all of his losses being by decision. In April 1941, he was drafted to the United States Army and participated in World War II.

Retirement, death and legacy
After his military service, Escobar confronted problems to meet the bantamweight's limit and retired. He became a spokesman for a liquor brand and relocated to New York temporally, with his family. Subsequently, he returned to Puerto Rico where he worked selling liquor in bars. In May 1947, Escobar and Jiménez Sicardó co-promoted a fight with the intention of bringing fans back to boxing. In the main event, Diego Sosa was matched against Francisco Colón García. Escobar was inducted into the Madison Square Garden's Boxing Hall of Fame in 1950. Escobar continued in his job as a liquor salesperson, during which it was common for liquor salesmen to drink a little bit of the product which they sold in front of potential customers. This contributed to the development of Escobar's alcoholic tendencies. His alcoholism would later combine with his diabetes and contribute to his death when he was 66 years old. Weeks before his death, Escobar participated in his last ceremony, where Diego Suárez, president of V. Suárez & Company. gave him a recognition. After his death, the town of Barceloneta honored his memory by a statue. His remains are interred at Cementerio Municipal Viejo in Barceloneta, according to a memorial written to honor his life. Escobar became the first world boxing champion in history to have a statue in his honor. On June 9, 2002, Escobar was inducted into the International Boxing Hall of Fame. He became the fourth Puerto Rican to receive this distinction and the first to be included in the "Old Timers" section. In March 2005, a second statue of Estobar was unveiled at the Estadio Sixto Escobar in San Juan. Among the celebrities that attended the ceremony were former boxing world champions Julian Solís and Alfredo Escalera. This statue's location served as a remembrance tribute during the 94th anniversary of Escobar's birth, when a flower crown was placed at its feet. During this date, an activity was presented by Puerto Rico's House of Boxing in the library of the Pabellón de la Fama del Deporte Puertorriqueño. Among those who attended the ceremony were Solís, Escalera and Iván Calderón. On this date, People Inc. presented a documentary covering his life, which was donated to the venue. Several buildings and streets were named after Escobar posthumously, including the Auditorio Sixto Escobar. The house where he lived was later turned into a library and museum bearing his name.

In 2019 Sixto Escobar was posthumously inducted to the Puerto Rico Veterans Hall of Fame.

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Sixto Escobar


text:
Tinnitus

Tinnitus is a variety of sound that is heard when no corresponding external sound is present. Nearly everyone experiences faint "normal tinnitus" in a completely quiet room; but it is of concern only if it is bothersome, interferes with normal hearing, or is associated with other problems. The word tinnitus comes from the Latin tinnire, "to ring". In some people, it interferes with concentration, and can be associated with anxiety and depression.

Tinnitus is usually associated with hearing loss and decreased comprehension of speech in noisy environments. It is common, affecting about 10–15% of people. Most tolerate it well, and it is a significant problem in only 1–2% of people. It can trigger a fight-or-flight response, as the brain may perceive it as dangerous and important.

Rather than a disease, tinnitus is a symptom that may result from a variety of underlying causes and may be generated at any level of the auditory system as well as outside that system. The most common causes are hearing damage, noise-induced hearing loss, or age-related hearing loss, known as presbycusis. Other causes include ear infections, disease of the heart or blood vessels, Ménière's disease, brain tumors, acoustic neuromas (tumors on the auditory nerves of the ear), migraines, temporomandibular joint disorders, exposure to certain medications, a previous head injury, and earwax. It can suddenly emerge during a period of emotional stress. It is more common in those with depression.

The diagnosis of tinnitus is usually based on a patient's description of the symptoms they are experiencing. Such a diagnosis is commonly supported by an audiogram, and an otolaryngological and neurological examination. How much tinnitus interferes with a person's life may be quantified with questionnaires. If certain problems are found, medical imaging, such as magnetic resonance imaging (MRI), may be performed. Other tests are suitable when tinnitus occurs with the same rhythm as the heartbeat. Rarely, the sound may be heard by someone other than the patient by using a stethoscope, in which case it is known as "objective tinnitus." Occasionally, spontaneous otoacoustic emissions, sounds produced normally by the inner ear, may result in tinnitus.

Measures to prevent tinnitus include avoiding chronic or extended exposure to loud noise, and limiting exposure to ototoxic drugs and substances. If there is an underlying cause, treating that cause may lead to improvements. Otherwise, typically, tinnitus management involves psychoeducation or counseling, such as talk therapy. Sound generators or hearing aids may help. No medication directly targets tinnitus.

Signs and symptoms
Tinnitus is often described as ringing, but it may also sound like clicking, buzzing, hissing, or roaring. It may be soft or loud, low- or high-pitched, and may seem to come from either one or both ears, or from the head itself. It may be intermittent or continuous. In some individuals, its intensity may be changed by shoulder, neck, head, tongue, jaw, or eye movements.

Course
Due to variations in study designs, data on the course of tinnitus shows few consistent results. Generally, prevalence increases with age in adults, and the ratings of annoyance decreases with.

Psychological effects
Although it is an annoying condition to which most people adapt, persistent tinnitus may cause anxiety and depression in some people. Tinnitus annoyance is more strongly associated with the psychological condition of the person than the loudness or frequency range of the perceived sound. Psychological problems such as depression, anxiety, sleep disturbances, and concentration difficulties are common in those with strongly annoying tinnitus. 45% of people with tinnitus have an anxiety disorder at some time in their lives.

Psychological research has focused on the tinnitus distress reaction to account for differences in tinnitus severity. The research indicates that conditioning at the initial perception of tinnitus linked it with negative emotions, such as fear and anxiety.

Types
Commonly tinnitus is classified into "subjective and objective tinnitus". Tinnitus is usually subjective, meaning that the sounds the person hears are not detectable by means currently available to physicians and hearing technicians. Subjective tinnitus has also been called "tinnitus aurium", "non-auditory", or "non-vibratory" tinnitus. In rare cases, tinnitus can be heard by someone else using a stethoscope. Even more rarely, in some cases it can be measured as a spontaneous otoacoustic emission (SOAE) in the ear canal. This is classified as objective tinnitus, also called "pseudo-tinnitus" or "vibratory" tinnitus.

Subjective tinnitus
Subjective tinnitus is the most frequent type. It can have many causes, but most commonly it results from hearing loss. When it is caused by disorders of the inner ear or auditory nerve, it can be called "otic" (from the Greek word for ear). These otological or neurological disorders include those triggered by infections, drugs, or trauma. A frequent cause is traumatic noise exposure that damages hair cells in the inner ear.. Some evidence suggests that long-term exposure to noise pollution from heavy traffic may increase the risk of developing tinnitus.

When there does not seem to be a connection with a disorder of the inner ear or auditory nerve, tinnitus can be called "non-otic". In 30% of cases, tinnitus is influenced by the somatosensory system; for instance, people can increase or decrease their tinnitus by moving their face, head, jaw, or neck. This type is called somatic or craniocervical tinnitus, since it is only head or neck movements that have an effect.

Some tinnitus may be caused by neuroplastic changes in the central auditory pathway. In this theory, the disturbance of sensory input caused by hearing loss results in such changes as a homeostatic response of neurons in the central auditory system, causing tinnitus. When some frequencies of sound are lost to hearing loss, the auditory system compensates by amplifying those frequencies, eventually producing sound sensations at those frequencies constantly even when there is no corresponding external sound.

Hearing loss
The most common cause of tinnitus is hearing loss. Hearing loss may have many different causes, but among those with tinnitus, the major cause is cochlear injury.

In many cases no underlying cause is identified.

Ototoxic drugs also may cause subjective tinnitus, as they may cause hearing loss, or increase the damage done by exposure to loud noise. This damage may occur even at doses not considered ototoxic. More than 260 medications have been reported to cause tinnitus as a side effect.

Tinnitus can also occur from the discontinuation of therapeutic doses of benzodiazepines. It can sometimes be a protracted symptom of benzodiazepine withdrawal and may persist for many months. Medications such as bupropion may also cause tinnitus.

Associated factors
Factors associated with tinnitus include:
 * Ear problems and hearing loss:
 * Conductive hearing loss
 * Acoustic shock
 * Loud noise or music
 * Middle ear effusion
 * Otitis
 * Otosclerosis
 * Eustachian tube dysfunction
 * Sensorineural hearing loss
 * Excessive or loud noise; e.g. acoustic trauma
 * Presbycusis (age-associated hearing loss)
 * Ménière's disease
 * Endolymphatic hydrops
 * Superior canal dehiscence
 * Acoustic neuroma
 * Mercury or lead poisoning
 * Ototoxic medications
 * Neurologic disorders:
 * Chiari malformation
 * Multiple sclerosis
 * Head injury
 * Giant cell arteritis
 * Temporomandibular joint dysfunction
 * Metabolic disorders:
 * Vitamin B12 deficiency
 * Iron deficiency anemia
 * Psychiatric disorders
 * Depression
 * Anxiety disorders
 * Other factors:
 * Vasculitis
 * Some psychedelic drugs can produce temporary tinnitus-like symptoms as a side effect:
 * 5-MeO-DET
 * Diisopropyltryptamine (DiPT)
 * Benzodiazepine withdrawal
 * Intracranial hyper or hypotension caused by, for example, encephalitis or a cerebrospinal fluid leak

Objective tinnitus
A specific type of tinnitus, objective tinnitus, is characterized by hearing the sounds of one's own muscle contractions or pulse, typically a result of sounds that have been created by the movement of jaw muscles or sounds related to blood flow in the neck or face. It is sometimes caused by an involuntary twitching of a muscle or a group of muscles (myoclonus) or by a vascular condition. In some cases, tinnitus is generated by muscle spasms around the middle ear.

Spontaneous otoacoustic emissions (SOAEs)—faint high-frequency tones that are produced in the inner ear and can be measured in the ear canal with a sensitive microphone—may also cause tinnitus. About 8% of those with SOAEs and tinnitus have SOAE-linked tinnitus, while the percentage of all cases of tinnitus caused by SOAEs is estimated at 4%.

Pediatric tinnitus
Children may be subject to pulsatile or continuous tinnitus, involving anomalies and variants of the vascular parts affecting the middle/inner ear structures. CT scans may be used to check the integrity of the structures, and MR scans can evaluate nerves and potential masses or malformations. Early diagnosis can prevent long-term impairments to development.

Pulsatile tinnitus
Some people experience a sound that beats in time with their pulse, known as pulsatile tinnitus or vascular tinnitus. Pulsatile tinnitus is usually objective in nature, resulting from altered blood flow or increased blood turbulence near the ear, such as from atherosclerosis or venous hum, but it can also arise as a subjective phenomenon from an increased awareness of blood flow in the ear.

The differential diagnosis for pulsatile tinnitus is wide and includes vascular etiologies, tumors, disorders of the middle ear or inner ear, and other intracranial pathologies. Vascular causes of pulsatile tinnitus include venous causes (e.g., high riding or dehiscent jugular bulb, sigmoid sinus diverticulum), arterial causes (e.g., cervical atherosclerosis, potentially life-threatening conditions such as carotid artery aneurysm or carotid artery dissection), or dural arteriovenous fistula or arteriovenous malformations. Pulsatile tinnitus may also indicate vasculitis, or more specifically, giant cell arteritis. Pulsatile tinnitus may also be caused by tumors such as paragangliomas (e.g., glomus tympanicum, glomus jugulare) or hemangiomas (e.g., facial nerve or cavernous). Middle ear causes of pulsatile tinnitus include patulous eustachian tube, otosclerosis, or middle ear myoclonus (e.g., stapedial or tensor tympani myoclonus). The most common inner ear cause of pulsatile tinnitus is superior semicircular canal dehiscence. Pulsatile tinnitus may also indicate idiopathic intracranial hypertension. Pulsatile tinnitus can be a symptom of intracranial vascular abnormalities and should be evaluated for irregular noises of blood flow (bruits).

Pathophysiology
Tinnitus may be caused by increased neural activity in the auditory brainstem, where the brain processes sounds, causing some auditory nerve cells to become overexcited. The basis of this theory is that many with tinnitus also have hearing loss.

Three reviews in 2016 emphasized the large range and possible combinations of pathologies involved in tinnitus, which result in a great variety of symptoms and specifically adapted therapies.

Diagnosis
The diagnostic approach is based on a history of the condition and an examination of the head, neck, and neurological system. Typically an audiogram is done, and occasionally medical imaging or electronystagmography. Treatable conditions may include middle ear infection, acoustic neuroma, concussion, and otosclerosis.

Evaluation of tinnitus can include a hearing test (audiogram), measurement of acoustic parameters of the tinnitus like pitch and loudness, and psychological assessment of comorbid conditions like depression, anxiety, and stress that are associated with severity of the tinnitus.

One definition of tinnitus, in contrast to normal ear noise experience, is that tinnitus lasts five minutes at least twice a week. However, people with tinnitus often experience the noise more frequently than this. Tinnitus can be present constantly or intermittently. Some people with constant tinnitus might not be aware of it all the time, but only, for example, during the night when there is less environmental noise to mask it. Chronic tinnitus can be defined as tinnitus with a duration of six months or more.

Audiology
Since most people with tinnitus also have hearing loss, a pure tone hearing test resulting in an audiogram may help diagnose a cause. An audiogram may also facilitate fitting of a hearing aid in those cases where hearing loss is significant. The pitch of tinnitus is often in the range of the hearing loss.

Psychoacoustics
Acoustic qualification of tinnitus includes measurement of several acoustic parameters like frequency in cases of monotone tinnitus or frequency range and bandwidth in cases of narrow band noise tinnitus, loudness in dB above hearing threshold at the indicated frequency, mixing-point, and minimum masking level. In most cases, tinnitus pitch or frequency range is between 5 kHz and 10 kHz, and loudness between 5 and 15 dB above the hearing threshold.

Another relevant parameter of tinnitus is residual inhibition: the temporary suppression or disappearance of tinnitus following a period of masking. The degree of residual inhibition may indicate how effective tinnitus maskers would be as treatment.

An assessment of hyperacusis, a frequent accompaniment of tinnitus, may also be made. Hyperacusis is related to negative reactions to sound and can take many forms. One parameter that can be measured is Loudness Discomfort Level (LDL) in dB, the subjective level of acute discomfort at specified frequencies over the frequency range of hearing. This defines a dynamic range between the hearing threshold at that frequency and the loudness discomfort level. A compressed dynamic range over a particular frequency range can be associated with hyperacusis. Normal hearing threshold is generally defined as 0–20 decibels (dB). Normal loudness discomfort levels are 85–90+ dB, with some authorities citing 100 dB. A dynamic range of 55 dB or less is indicative of hyperacusis.

Severity
Tinnitus is often rated on a scale from "slight" to "severe" according to the effects it has, such as interference with sleep, quiet activities, and normal daily activities.

Assessment of psychological processes related to tinnitus involves measurement of tinnitus severity and distress, as measured subjectively by validated self-report tinnitus questionnaires. Such questionnaires measure the degree of psychological distress and handicap associated with tinnitus, including effects on hearing, lifestyle, health, and emotional functioning. A broader assessment of general functioning, such as levels of anxiety, depression, stress, life stressors, and sleep difficulties, is also important in the assessment of tinnitus due to higher risk of negative well-being across these areas, which may be affected by or exacerbate the tinnitus symptoms. Current assessment measures aim to identify levels of distress and interference, coping responses, and perceptions of tinnitus to inform treatment and monitor progress. However, wide variability, inconsistencies, and lack of consensus regarding assessment methodology are evidenced in the literature, limiting comparison of treatment effectiveness. Developed to guide diagnosis or classify severity, most tinnitus questionnaires have been shown to be treatment-sensitive outcome measures.

Pulsatile tinnitus
If examination reveals a bruit (sound due to turbulent blood flow), imaging studies such as transcranial doppler (TCD) or magnetic resonance angiography (MRA) should be performed.

Differential diagnosis
Other potential sources of the sounds normally associated with tinnitus should be ruled out. For instance, two recognized sources of high-pitched sounds might be electromagnetic fields common in modern wiring and various sound signal transmissions. A common and often misdiagnosed condition that mimics tinnitus is radio frequency (RF) hearing, in which subjects hear objectively audible high-pitched transmission frequencies that sound similar to tinnitus.

Prevention
Prolonged exposure to loud sound or noise levels can lead to tinnitus. Custom made ear plugs or other measures can help with prevention. Employers may use hearing loss prevention programs to help educate and prevent dangerous levels of exposure to noise. Government organizations set regulations to ensure employees, if following the protocol, should have minimal risk to permanent damage to their hearing.

Certain groups are advised to wear ear plugs to avoid the risk of tinnitus, such as that caused by overexposure to loud noises like wind noise for motorcycle riders. This includes military personnel, musicians, DJs, agricultural workers, and construction workers as people in those occupations are at a greater risk compared to the general population.

Several medicines have ototoxic effects, which can have a cumulative effect that increases the damage done by noise. If ototoxic medications must be administered, close attention by the physician to prescription details, such as dose and dosage interval, can reduce the damage done.

Management
If a specific underlying cause is determined, treating it may lead to improvements. Otherwise, the primary treatment for tinnitus is talk therapy, sound therapy, or hearing aids. There are no effective drugs that treat tinnitus.

Psychological
The best-supported treatment for tinnitus is cognitive behavioral therapy (CBT). It decreases the stress those with tinnitus feel. This appears to be independent of any effect on depression or anxiety. Acceptance and commitment therapy (ACT) also shows promise in the treatment of tinnitus. Relaxation techniques may also help. A clinical protocol called Progressive Tinnitus Management has been developed by the United States Department of Veterans Affairs.

Sound-based interventions
The application of sound therapy by either hearing aids or tinnitus maskers may help the brain ignore the specific tinnitus frequency. Although these methods are poorly supported by evidence, there are no negative effects. There are several approaches for tinnitus sound therapy. The first is sound modification to compensate for the individual's hearing loss. The second is a signal spectrum notching to eliminate energy close to the tinnitus frequency. There is some tentative evidence supporting tinnitus retraining therapy, which aims to reduce tinnitus-related neuronal activity. An alternative tinnitus treatment uses mobile applications that include various methods including masking, sound therapy, and relaxation exercises. Such applications can work as a separate device or as a hearing aid control system.

Neuromonics is another sound-based intervention. Its protocol follows the principle of systematic desensitization and involves a structured rehabilitation program lasting 12 months. Neuromonics therapy employs customized sound signals delivered through a device worn by the patient, which aims to target the specific frequency range associated with their tinnitus perception.

Medications
there were no medications effective for idiopathic tinnitus. There is not enough evidence to determine if antidepressants or acamprosate are useful. There are conflicting studies regarding the effectiveness of benzodiazepines for tinnitus. Usefulness of melatonin, as of 2015, is unclear. It is unclear if anticonvulsants are useful for treating tinnitus. Steroid injections into the middle ear also do not seem to be effective. There is no evidence to suggest that the use of betahistine to treat tinnitus is effective.

Botulinum toxin injection has succeeded in some of the rare cases of objective tinnitus from a palatal tremor.

Caroverine is used in a few countries to treat tinnitus. The evidence for its usefulness is very weak.

Neuromodulation
In 2020, information about clinical trials indicated that bimodal neuromodulation may reduce the symptoms of tinnitus. It is a noninvasive technique that involves applying an electrical stimulus to the tongue while also administering sounds. Equipment associated with the treatments is available through physicians. Studies with it and similar devices continue in several research centers.

Some evidence supports neuromodulation techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, and neurofeedback.

In June 2024, The US Food and Drug Administration (FDA) approved the Neuromod's Lenire device for tinnitus treatment option for the 2.9 million US Veterans living with tinnitus. The drug will be administered through the Department of Veterans Affairs (VA), making it the first bimodal neuromodulation device to be awarded a Federal Supply Schedule (FSS) Contract from the US Government.

Alternative medicine
Ginkgo biloba does not appear to be effective. The American Academy of Otolaryngology recommends against taking melatonin or zinc supplements to relieve symptoms of tinnitus, and reported that evidence for the efficacy of many dietary supplements (such as lipoflavonoids, garlic, traditional Chinese/Korean herbal medicine, honeybee larvae, and various other vitamins and minerals, as well as homeopathic preparations) did not exist. A 2016 Cochrane Review also concluded that evidence was not sufficient to support taking zinc supplements to reduce symptoms associated with tinnitus.

Prognosis
While there is no cure, most people with tinnitus get used to it over time; for a minority, it remains a significant problem.

Adults
Tinnitus affects 10–15% of people. About a third of North Americans over 55 experience it. It affects one third of adults at some time in their lives, whereas 10–15% are disturbed enough to seek medical evaluation. 70 million people in Europe are estimated to have tinnitus.

Children
Tinnitus is commonly thought of as a symptom of adulthood, and is often overlooked in children. Children with hearing loss have a high incidence of pediatric tinnitus, even though they do not express the condition or its effect on their lives. Children do not generally report tinnitus spontaneously and their complaints may not be taken seriously. Among those who do complain, there is an increased likelihood of associated otological or neurological pathology such as migraine, juvenile Meniere's disease, or chronic suppurative otitis media. Its reported prevalence varies from 12 to 36% in children with normal hearing thresholds, and up to 66% in children with a hearing loss. Approximately 3–10% of children have been reported to be troubled by tinnitus.

title: Tinnitus


text:
Andrew Goodman (activist)

Andrew Goodman (November 23, 1943 – June 21, 1964) was an American civil rights activist. He was one of three Congress of Racial Equality (CORE) workers murdered in Philadelphia, Mississippi, by members of the Ku Klux Klan in 1964. Goodman and two fellow activists, James Chaney and Michael Schwerner, were volunteers for the Freedom Summer campaign that sought to register African-Americans to vote in Mississippi and to set up Freedom Schools for black Southerners.

Early life and beginnings of activism
Andrew Goodman was born on November 23, 1943, in New York City, the second of three boys born to Robert, a writer and civil engineer, and Carolyn Goodman, a psychologist and social activist. He grew up in the city's Upper East Side. Goodman was Jewish, like fellow civil rights activist Michael Schwerner, alongside whom Goodman would be murdered. Goodman's neighborhood was a racially-mixed community of white, black, and Hispanic families.

The Goodman family was involved in intellectual and socially progressive activism and were devoted to social justice. His mother Carolyn was a lifelong labor activist. In her youth, she helped farm workers to organize and was active in community efforts to support the Republican faction during the Spanish Civil War in the 1930s.

Andrew followed his parents' activist bent from a young age. At the age of 14, Goodman traveled to Washington, D.C., to participate in the 1958 Youth March for Integrated Schools. During the march, approximately 10,000 high school age students promoted the desegregation of American public schools after the U.S. Supreme Court's Brown v. Board of Education landmark decision in 1954 struck down the constitutionality of racial segregation in public schools. The next year, Goodman and a friend went to West Virginia to live in a coal mining town and sought to advocate to the governor over the poor working conditions there. At 17, Goodman traveled to Western Europe to understand the impact of largescale agribusiness on small farmers. Goodman also participated in a 1960 protest at a New York Woolworth's as part of the sit-in movement protesting the segregationist policies of the five-and-dime store.

In 1961, Goodman graduated high school from the progressive Walden School, where he had attended from the age of 3. At Walden, he was involved in the theater program. He also arranged for Brooklyn Dodger Jackie Robinson, a neighbor of his and the first African-American to play in Major League Baseball, to speak at the school. After Walden, Goodman enrolled the Honors Program at the University of Wisconsin–Madison and considered a drama major, but withdrew after one semester after falling ill with pneumonia. He returned to New York City to improve his health and was selected for a role in the Off-Broadway play The Chief Thing by Russian dramatist Nikolaí Evreninov.

Goodman then enrolled at Queens College, New York City, and majored in anthropology. At Queens, he was a friend and classmate of Paul Simon. He developed an interest in poetry. One of his poems, "A Corollary to a Poem by A. E. Housman," was posthumously discovered by his college professor Mary Doyle Curran and published in the Massachusetts Review and the New York Times. With Goodman's brief acting experience, he originally planned to study drama but switched to anthropology. Goodman's growing interest in anthropology seemed to parallel his increasing political seriousness. Throughout college, Goodman acted with an Off-Broadway repertory company.

Participation in Freedom Summer
"The senators could not persist in this polite debate over the future dignity of a human race if the white Northerners were not so shockingly apathetic." In the spring of 1964, his junior year at Queens College, Goodman attended a talk by Mississippi civil rights activists Aaron Henry, head of the state's NAACP branch, and Fannie Lou Hamer. Henry and Hamer were recruiting students under the age of 21, who with the permission of their parents, would participate in the Freedom Summer project to help register African-Americans to vote in Mississippi and to set up Freedom Schools.

In June 1964, Goodman left New York to teach at a Congress of Racial Equality (CORE) training session for Freedom Summer volunteers at the Western College for Women (now part of Miami University) in Oxford, Ohio. In Ohio, Goodman met fellow New Yorker 24 year old Michael Schwerner, an experienced volunteer with CORE, and 21 year old James Chaney, a CORE activist in Mississippi. The three trained hundreds of Freedom Summer volunteers, mostly students, how to navigate the racism and violence they would encounter in Mississippi. At the training, Schwerner learned that one of the Freedom Schools in Mississippi that he had helped to organize at the Mount Zion Methodist Church in Philadelphia had been burned down by the Ku Klux Klan (KKK). To investigate, the three men left Ohio for Mississippi by car on June 20.

Arrest and murder

On June 21, their first full day in the state, the trio drove from their home base of Meridian for Philadelphia, a community about an hour from Meridian, to visit the church ruins and meet with church members. When they were driving back to Meridian, their home base, they were pulled over by Neshoba County, Mississippi Deputy Sheriff Cecil Price (a KKK member), for allegedly driving 65 miles-per-hour in a 30-mile-per-hour speed limit zone. Price arrested the three men and took them to the Neshoba County jail, where Chaney was booked for speeding, while Schwerner and Goodman were booked "for investigation". Chaney was charged a $20 fine and the three men were released around 10:30pm on and instructed to leave the county. However, while Chaney, Schwerner, and Goodman were in custody, Price contacted local KKK leader and minister Edgar Ray Killen and informed him of the three activists in custody. According to a subsequent U.S. Department of Justice investigation, Killen then gathered other KKK members and devised a plot to attack the three as they left the jail.

Price followed them in his patrol car. At 10:25, Price sped to catch up with the station wagon before it crossed the border into the relative safety of Lauderdale County. Price ordered the three out of their car and into his. He drove them to a deserted area on Rock Cut Road while followed by two cars filled with other Klansmen. Price turned the trio over to the Klansmen who, after beating Chaney, shot and killed Schwerner, Goodman, and Chaney. An autopsy of Goodman, showing fragments of red clay in his lungs and grasped in his fists, suggests he was probably buried alive alongside the already dead Chaney and Schwerner.

The Mississippi State Sovereignty Commission was strongly opposed to integration and civil rights. It paid spies to identify citizens suspected of activism, especially people from the North and West who entered the state. The records opened by court order in 1998 also revealed the state's deep complicity in the murders of Chaney, Goodman, and Schwerner, because its investigator A. L. Hopkins passed on to the Commission information about the workers, including the car license number of a new civil rights worker. Records showed the Commission, in turn, passed the information on to the Neshoba County Sheriff, who was implicated in the murders.

Investigation and trial
The murders changed the course of the Civil Rights Movement:

Willie Blue, a surviving participant in the Freedom Summer movement said: "Goodman's richer than whipped cream. He wasn't supposed to die in Vietnam; he sure wasn't supposed to die in Mississippi. When America's brightest are murdered for doing something fundamentally American, suddenly the world knows about Mississippi. It was another nail in the segregated coffin." The FBI entered the case after the men disappeared. They helped find them buried in an earthen dam. The US government prosecuted the case under the Enforcement Act of 1870. The Neshoba County deputy sheriff and six conspirators were convicted by Federal prosecutors of civil rights violations but were not convicted of murder. Two defendants were acquitted because the jury deadlocked.

Reinvestigation
Journalist Jerry Mitchell, an award-winning investigative reporter for the Jackson Clarion-Ledger, had written extensively about the case for many years. Mitchell, who had already earned fame for helping secure convictions in several other high-profile civil rights era murder cases, including the assassination of Medgar Evers in Jackson, Mississippi, the Birmingham, Alabama 16th Street Baptist Church bombing, and the murder of Vernon Dahmer in Mississippi, developed new evidence, found new witnesses and pressured the state to take action. Barry Bradford, an Illinois high-school teacher later famous for helping clear the name of civil rights martyr Clyde Kennard, and three students, Allison Nichols, Sarah Siegel, and Brittany Saltiel, joined Mitchell's efforts.

Bradford and his students' documentary, produced for the National History Day contest, presented important new evidence and compelling reasons for reopening the Goodman, Chaney, and Schwerner case. They also obtained an interview with Edgar Ray Killen, which helped persuade the state to open the case for investigation. Mitchell was able to determine the identity of "Mr. X", the mystery informer who had helped the FBI discover the bodies and smash the conspiracy of the Klan in 1964, in part using evidence developed by Bradford and the students.

On January 7, 2005, Edgar Ray Killen was arrested. He was found guilty of three counts of manslaughter – not murder – on June 21, 2005, exactly 41 years to the day after the murders. He was sentenced to sixty years in prison—twenty years for each count, to be served consecutively. He appealed the verdict, but the sentence was upheld on April 12, 2007, by the Supreme Court of Mississippi. He died in prison on January 11, 2018, at age 92.

On June 20, 2016, just one day ahead of the 52nd anniversary of the murders, Attorney General Hood announced an end to the federal and state investigations into the 'Mississippi Murders', officially closing the case.

Legacy and honors
In 1966, Andrew's parents, Robert and Carolyn Goodman started The Andrew Goodman Foundation to carry on the spirit and purpose of their son's life. After the death of Robert Goodman in 1969, Carolyn continued the work of the Foundation, focusing on projects like a reverse march to Mississippi and a 25th Anniversary Memorial. The memorial, which took place at St. John The Divine Church in NYC, was attended by 10,000 people and was presided by Governor Mario Cuomo, Maya Angelou, Pete Seeger, Aaron Henry, Harry Belafonte, and others closely associated with the Civil Rights Movement. After Carolyn's death in August 2007, David Goodman, Andrew's younger brother, and Sylvia Golbin Goodman, David's wife, took up the work of the Foundation.

For nearly 50 years, the organization was a private foundation acting in the public interest. With their eyes set on the future, the Board of Trustees of The Andrew Goodman Foundation elected to turn the organization into a public charity in 2012. In 2014, on the fiftieth anniversary of the murders, the Foundation officially launched Vote Everywhere program designed to support college students who are continuing the work of Freedom Summer.

Goodman

 * In 2002, a 2,176-foot peak in the Adirondack Mountains town of Tupper Lake, New York, was officially named Goodman Mountain in Goodman's memory. Goodman's family had spent summers there for 30 years.
 * The Walden School, in Manhattan, named its middle and upper school building in Goodman's memory. The Trevor Day School now occupies the building and has maintained the building's name as the "Andrew Goodman Building".
 * Goodman, along with Chaney and Schwerner, received a posthumous Presidential Medal of Freedom from President Barack Obama in 2014.
 * The Chaney-Goodman-Schwerner Clock Tower of Rosenthal Library, is named in honor of James, Andrew, and Mickey on the CUNY Queens College Campus in New York City.
 * The song "He Was My Brother", released in 1964 by Simon & Garfunkel, is a dedication to Goodman along with two other civil rights activists.

title: Andrew Goodman (activist)