Prolactin induced protein (called GCDFP-15 in this context) in breast cyst fluid or breast tissue serves as marker of both benign and malignant apocrine metaplasia as the protein is not normally expressed in breast tissue. [ 16 ] [ 17 ]  It is characteristic of low grade apocrine carcinoma of the breast, high grade apocrine carcinoma frequently lose expression of this marker. [ 18 ]
PIP gene expression in breast cancer lines was associated with decreased cell proliferation and invasiveness and an increase of the apoptotic pathway. Many of the genes affected by PIP appear to be regulated by  STAT5 . [ 19 ]


A mitogenic effect of this protein on experimental breast cells lines MCF10A, MCF7, BT474, MDA-MB231 and T47D  was detected. [ 15 ]  Prolactin-induced protein has also been used for identification and detection of disseminated  breast cancer  cells. [ 20 ]


The PIP gene is amplified in some breast cancer lines accounting for some of its overexpression, however additional mechanisms are needed to completely explain its overexpression. [ 21 ]
In T47D breast cancer cells, androgen receptor and  RUNX2  interact to synergistically enhance PIP expression. [ 22 ]


In molecular apocrine breast cancer (ER-/AR+) there is a positive feedback loop between  androgen receptor  and  extracellular signal-regulated kinase  (ERK) via  CREB1  which can be inhibited by anti-androgens. PIP expression is necessary for viability and invasiveness of this subtype of breast cancer. [ 23 ]


In ER+ breast cancer, particularly those with very high level of ER expression, PIP appears to play an important role in proliferation and invasion as well as acquired resistance to  tamoxifen . [ 24 ]


Psoriasis  is a long-lasting, noncontagious  autoimmune disease  characterized by  patches of abnormal skin . [ 4 ] [ 5 ]  These areas are  red , pink, or purple,  dry ,  itchy , and scaly. [ 8 ] [ 3 ]  Psoriasis varies in severity from small localized patches to complete body coverage. [ 3 ]   Injury  to the skin can trigger psoriatic skin changes at that spot, which is known as the  Koebner phenomenon . [ 9 ]


The five main types of psoriasis are plaque,  guttate ,  inverse ,  pustular , and  erythrodermic . [ 5 ]  Plaque psoriasis, also known as psoriasis vulgaris, makes up about 90% of cases. [ 4 ]  It typically presents as red patches with white scales on top. [ 4 ]  Areas of the body most commonly affected are the back of the forearms, shins, navel area, and scalp. [ 4 ]  Guttate psoriasis has drop-shaped lesions. [ 5 ]  Pustular psoriasis presents as small, noninfectious,  pus -filled blisters. [ 10 ]  Inverse psoriasis forms red patches in skin folds. [ 5 ]  Erythrodermic psoriasis occurs when the rash becomes very widespread and can develop from any of the other types. [ 4 ]   Fingernails  and toenails are affected in most people with psoriasis at some point in time. [ 4 ]  This may include pits in the nails or changes in nail color. [ 4 ]


Psoriasis is generally thought to be a  genetic disease  that is triggered by environmental factors. [ 3 ]  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 . [ 4 ]  This suggests that genetic factors predispose to psoriasis. [ 4 ]  Symptoms often worsen during winter and with certain medications, such as  beta blockers  or  NSAIDs . [ 4 ]  Infections and  psychological stress  can also play a role. [ 3 ] [ 5 ]  The underlying mechanism involves the  immune system  reacting to  skin cells . [ 4 ]  Diagnosis is typically based on the signs and symptoms. [ 4 ]


There is no known cure for psoriasis, but various treatments can help control the symptoms. [ 4 ]  These treatments include  steroid creams ,  vitamin D 3  cream,  ultraviolet light ,  immunosuppressive drugs , such as  methotrexate , and  biologic  therapies targeting specific immunologic pathways. [ 5 ]  About 75% of skin involvement improves with creams alone. [ 4 ]  The disease affects 2–4% of the population. [ 7 ]  Men and women are affected with equal frequency. [ 5 ]  The disease may begin at any age, but typically starts in adulthood. [ 5 ]  Psoriasis is associated with an increased risk of  psoriatic arthritis ,  lymphomas ,  cardiovascular disease ,  Crohn's disease , and  depression . [ 4 ]  Psoriatic arthritis affects up to 30% of individuals with psoriasis. [ 10 ]


The word "psoriasis" is from  Greek  ψωρίασις, meaning "itching condition" or "being itchy" [ 11 ]  from  psora , "itch", and  -iasis , "action, condition".


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. [ 12 ]  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. [ 12 ] [ 13 ]


Additional types of psoriasis comprise about 10% of cases. They include pustular, inverse, napkin, guttate, oral, and seborrheic-like forms. [ 14 ]


Pustular psoriasis  appears as raised bumps filled with noninfectious pus ( pustules ). [ 15 ]  The skin under and surrounding the pustules is red and tender. [ 16 ]  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. [ 17 ]


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. [ 18 ]


Napkin psoriasis  is a subtype of psoriasis common in infants under the age of two and is characterized by red papules with silver scales in the diaper area that may extend to the torso or limbs. [ 19 ] [ 20 ]  Napkin psoriasis is often misdiagnosed as  napkin dermatitis  (diaper rash). [ 21 ]  It typically improves as children age and may later present in more common forms as  plaque psoriasis  or  inverse psoriasis . [ 22 ]


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 spare 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. [ 23 ]  Skin biopsy can also be performed which typically shows a psoriasiform reaction pattern characterized by epidermal hyperplasia with elongation of the rete ridges. [ 23 ]


There is no firm evidence regarding the best management for guttate psoriasis; however, first-line therapy for mild guttate psoriasis typically includes topical corticosteroids. [ 23 ] [ 24 ]  Phototherapy can be used for moderate or severe guttate psoriasis. Biologic treatments have not been well studied in the treatment of guttate psoriasis. [ 23 ]


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. [ 23 ] [ 18 ]


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. [ 17 ]  It may be accompanied by severe dryness, itching, swelling, and pain. It can develop from any type of psoriasis. [ 17 ]  It is often the result of an exacerbation of unstable plaque psoriasis, particularly following the abrupt withdrawal of systemic  glucocorticoids . [ 25 ]  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. [ 26 ]


Psoriasis in the mouth is very rare, in contrast to  lichen planus , another common papulosquamous disorder that commonly involves both the skin and mouth. [ 27 ]  When psoriasis involves the oral mucosa (the lining of the mouth), it may be asymptomatic, [ 27 ]  but it may appear as white or grey-yellow plaques. [ 27 ]   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. [ 28 ]  A recent study found an association between the two conditions, and it suggests that geographic tongue might be a predictor to psoriasis. [ 29 ]


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 . [ 19 ]


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. [ 30 ] [ 31 ]  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 . [ 30 ]  Psoriatic arthritis can also affect the hips, knees, spine ( spondylitis ), and  sacroiliac joint  ( sacroiliitis ). [ 32 ]  About 30% of individuals with psoriasis will develop psoriatic arthritis. [ 12 ]  Skin manifestations of psoriasis tend to occur before arthritic manifestations in about 75% of cases. [ 31 ]


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. [ 33 ]  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. [ 33 ]


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 the scale is removed),  Koebner phenomenon  (psoriatic skin lesions induced by trauma to the skin), [ 19 ]  and  itching  and pain localized to papules and plaques. [ 18 ] [ 19 ]


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. [ 34 ] [ 35 ]


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. [ 36 ]


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. [ 37 ]


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. [ 37 ]   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. [ 37 ]


The major determinant is  PSORS1 , which probably accounts for 35–50% of psoriasis heritability. [ 38 ]  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 , [ 34 ]  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. [ 37 ]


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. [ 34 ]  T cells are involved in the inflammatory process that leads to psoriasis. [ 37 ]  These genes are on the pathway that upregulates tumor necrosis factor-α and  nuclear factor κB , two genes involved in inflammation. [ 37 ]  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). [ 39 ] [ 40 ]


Conditions reported as worsening the disease include chronic infections, stress, and changes in season and  climate . [ 34 ]  Other factors that might worsen the condition include hot water, scratching psoriasis skin lesions,  skin dryness , excessive alcohol consumption,  cigarette smoking , and obesity. [ 34 ] [ 41 ] [ 42 ] [ 43 ]  The effects of stopping cigarette smoking or alcohol misuse have yet to be studied as of 2019. [ 43 ]


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. [ 44 ]  A much higher rate of psoriatic arthritis occurs in HIV-positive individuals with psoriasis than in those without the infection. [ 44 ]  The immune response in those infected with HIV is typically characterized by  cellular signals  from  T h 2 subset of CD4+ helper T cells , [ 45 ]  whereas the immune response in psoriasis vulgaris is characterized by a pattern of cellular signals typical of  T h 1 subset of CD4+ helper T cells  and  T h 17 helper T cells . [ 46 ] [ 47 ]  The diminished CD4+-T cell presence is thought to cause 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. [ 48 ]  In those with long-term, well-controlled psoriasis, new HIV infection can trigger a severe flare-up of psoriasis and/or psoriatic arthritis. [ medical citation needed ]


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 . [ 35 ]  Guttate psoriasis often affects children and adolescents and can be triggered by a recent  group A streptococcal infection  (tonsillitis or pharyngitis). [ 17 ]


Drug-induced psoriasis may occur with  beta blockers , [ 10 ]   lithium , [ 10 ]   antimalarial medications , [ 10 ]   nonsteroidal anti-inflammatory drugs , [ 10 ]   terbinafine ,  calcium channel blockers ,  captopril ,  glyburide ,  granulocyte colony-stimulating factor , [ 10 ]   interleukins ,  interferons , [ 10 ]   lipid-lowering medications , [ 14 ] : 197   and paradoxically  TNF inhibitors  such as  infliximab  or  adalimumab . [ 49 ]  Withdrawal of  corticosteroids  (topical steroid cream) can aggravate psoriasis due to the  rebound effect . [ 50 ]


Psoriasis is characterized by an abnormally excessive and rapid growth of the  epidermal layer of the skin . [ 51 ]  Abnormal production of skin cells (especially during  wound repair ) and an overabundance of skin cells result from the sequence of pathological events in psoriasis. [ 16 ]  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. [ 37 ] [ 17 ]  Skin cells are replaced every 3–5 days in psoriasis rather than the usual 28–30 days. [ 52 ]  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 immune cells). [ 12 ] [ 44 ]  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 . [ 37 ] [ 53 ]  These secreted inflammatory signals are believed to stimulate keratinocytes to proliferate. [ 37 ]  One hypothesis is that psoriasis involves a defect in  regulatory T cells , and in the regulatory cytokine  interleukin-10 . [ 37 ]  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. [ 17 ]


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. [ 54 ] [ 55 ]


Deoxyribonucleic acid  (DNA) released from dying cells acts as an inflammatory stimulus in psoriasis [ 56 ]  and stimulates the receptors on certain dendritic cells, which in turn produce the cytokine interferon-α. [ 56 ]  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. [ 37 ]


Dendritic cells  bridge the  innate immune system  and  adaptive immune system . They are increased in psoriatic lesions [ 51 ]  and induce the proliferation of T cells and type 1 helper T cells (T h 1). Targeted immunotherapy, as well as  psoralen  and  ultraviolet A  ( PUVA ) therapy, can reduce the number of dendritic cells and favors a  T H 2 cell  cytokine secretion pattern over a T h 1/T h 17 cell cytokine profile. [ 37 ] [ 46 ]  Psoriatic T cells move from the dermis into the epidermis and secrete interferon-γ and  interleukin-17 . [ 57 ]  Interleukin-23 is known to induce the production of interleukin-17 and interleukin-22. [ 51 ] [ 57 ]  Interleukin-22 works in combination with interleukin-17 to induce keratinocytes to secrete  neutrophil -attracting cytokines. [ 57 ]


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. [ 18 ]  No special blood tests or diagnostic procedures are usually required to make the diagnosis. [ 16 ] [ 59 ]


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). [ 50 ]  Dermatologic manifestations of systemic illnesses such as the rash of  secondary syphilis  may also be confused with psoriasis. [ 50 ]


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. [ 16 ] [ 60 ]  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. [ 16 ]  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 joints. [ 16 ]


Psoriasis is classified as a  papulosquamous disorder  and is most commonly subdivided into different categories based on histological characteristics. [ 3 ] [ 10 ]  Variants include plaque, pustular, guttate, and flexural psoriasis. Each form has a dedicated  ICD-10  code. [ 61 ]  Psoriasis can also be classified into nonpustular and  pustular  types. [ 62 ]


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 . [ 63 ]  Type 1 accounts for about 75% of persons with psoriasis. [ 64 ]


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 [ 16 ] [ 34 ] [ 65 ]  while others have classified them as distinct from autoimmune diseases and referred to them as  immune-mediated inflammatory diseases . [ 37 ] [ 66 ] [ 67 ]


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. [ 68 ]  Moderate to severe psoriasis was defined by the same group as BSA >10 or PASI score >10 and a DLQI score >10. [ 68 ]


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. [ 69 ]


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). [ 70 ]  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. [ 71 ]


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. [ 72 ]  Additionally, the co-morbidities increase the treatment and financial burden of psoriasis and should be considered when managing this condition. [ 72 ]


There is 2.2 times increased risk of cardiovascular complications in people with psoriasis. [ 73 ]  Also, people with psoriasis are more susceptible to myocardial infarction (heart attack) and stroke. [ 73 ]  It has been speculated that there is systemic inflammation in psoriasis, which drives “psoriatic march” and can cause other inflammatory complications including cardiovascular complications. [ 73 ]  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 an 11% reduction in aortic vascular inflammation when there is a 75% reduction in the PASI score. [ 74 ]


Depression or depressive symptoms are present in 28–55% of people with psoriasis. [ 75 ]  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. [ 75 ]  There is some evidence that increased inflammatory signals in the body could also contribute to depression in people with chronic inflammatory diseases, including psoriasis. [ 75 ]


People with psoriasis are at increased risk of developing  type 2 diabetes  (~1.5 odds ratio). [ 76 ]  A genome-wide 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. [ 76 ]


While no cure is available for psoriasis, [ 50 ]  many treatment options exist. Topical agents are typically used for mild disease, phototherapy for moderate disease, and systemic agents for severe disease. [ 77 ]  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. [ 78 ]


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 . [ 79 ]  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. [ 80 ]


Vitamin D analogues  (such as  paricalcitol ,  calcipotriol ,  tacalcitol , and  calcitriol ) are superior to placebo. Combination therapy with vitamin D and a corticosteroid is superior to either treatment alone and  vitamin D  is superior to coal tar for chronic plaque psoriasis. [ 81 ]


For psoriasis of the scalp, a 2016 review found dual therapy (vitamin D analogs and topical corticosteroids) or corticosteroid monotherapy to be more effective and safer than topical vitamin D analogs alone. [ 82 ]  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. [ 82 ]


Moisturizers and emollients such as  mineral oil ,  petroleum jelly , and  decubal  (an oil-in-water emollient) were found to increase the clearance of psoriatic plaques. Some emollients are even more effective at clearing psoriatic plaques when combined with phototherapy. [ 83 ]  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. [ 83 ]  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 D 3  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.) [ 41 ] [ 84 ]


Vitamin D analogs may be useful with steroids; steroids alone have a higher rate of side effects. [ 81 ]  Vitamin D analogs may allow lower doses of steroids to be used. [ 85 ]


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. [ 86 ]  Decreases of PASI scores greater than 75% and remission for several months have commonly been observed. [ 86 ]  Side effects may be mild such as itchiness,  folliculitis ,  sunburn ,  poikiloderma , and a theoretical risk of nonmelanoma cancer or melanoma has been suggested. [ 86 ]  Some studies indicate no increased risk of melanoma in the long term. [ 87 ]  Data are inconclusive concerning 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 . [ 87 ]  Dead Sea balneotherapy is also effective for psoriatic arthritis. [ 87 ]  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. [ 88 ]   Glycerin  is also an effective treatment for Psoriasis. [ 89 ]


Phototherapy  in the form of  sunlight  has long been used for psoriasis. [ 77 ]  UVB wavelengths of 311–313  nanometers  are most common. These lamps have been developed for this treatment. [ 77 ]  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. [ 77 ]  Increased rates of cancer from treatment appear to be small. [ 77 ]   Narrowband UVB therapy  has been demonstrated to have similar efficacy to  psoralen and ultraviolet A phototherapy  (PUVA). [ 90 ]  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. [ 91 ]


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. [ 92 ]


UV light therapies all have risks; tanning beds are no exception, being listed by the  World Health Organization  as carcinogens. [ 93 ]  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. [ 92 ]


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. [ 90 ]  The activity of many types of immune cells found in the skin is also effectively suppressed by NB-UVB phototherapy treatments. [ 94 ]  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. [ 90 ]


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 ). [ 42 ] [ 95 ]  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 . [ 96 ]


Psoriasis resistant to  topical treatment  and  phototherapy  may be treated with systemic therapies including  medications  by mouth or  injectable treatments . [ 97 ]  People undergoing systemic treatment must have regular  blood  and  liver function tests  to check for medication toxicities. [ 97 ]   Pregnancy  must be avoided for most of these treatments. [ medical citation needed ]  The majority of people experience a recurrence of psoriasis after systemic treatment is discontinued. [ medical citation needed ]


Non-biologic systemic treatments frequently used for psoriasis include  methotrexate ,  ciclosporin ,  hydroxycarbamide ,  fumarates  such as  dimethyl fumarate , and  retinoids . [ 98 ]  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 . [ 25 ]  Oral  corticosteroids  should not be used as they can severely flare psoriasis upon their discontinuation. [ 99 ]


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. [ 98 ]  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. [ 98 ] [ 100 ]  However, due to their immunosuppressive actions, biologics have been associated with a small increase in the risk for infection. [ 98 ]


Guidelines regard biologics as a third-line treatment for plaque psoriasis following inadequate response to topical treatment, phototherapy, and non-biologic systemic treatments. [ 100 ]  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 . [ 98 ]


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 , [ 101 ]  have been developed against pro-inflammatory cytokines [ 102 ]  and inhibit the inflammatory pathway at a different point than the anti-TNF-α antibodies. [ 37 ]  IL-12 and IL-23 share a common domain,  p40 , which is the target of the  FDA-approved   ustekinumab . [ 34 ]  In 2017 the  US FDA  approved  guselkumab  for plaque psoriasis. [ 103 ]  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. [ 104 ]


Two medications that target T cells are  efalizumab  and  alefacept . Efalizumab is a monoclonal antibody that specifically targets the  CD11a  subunit of  LFA-1 . [ 98 ]  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 . [ 98 ]  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. [ 37 ]   Apremilast  may also be used. [ 12 ]


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 . [ 105 ]


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. [ 106 ]  There is also some evidence to support use of  secukinumab ,  brodalumab ,  guselkumab , certolizumab, and ustekinumab. [ 107 ] [ 106 ]  In general, anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha biologics were found to be more effective than traditional systemic treatments. [ 106 ]  The immunologic pathways of psoriasis involve  Th9 ,  Th17 ,  Th1  lymphocytes, and  IL-22 . The aforementioned biologic agents hinder different aspects of these pathways. [ citation needed ]


Another set of treatments for moderate to severe psoriasis are  fumaric acid esters  (FAE), which may be similar in effectiveness to  methotrexate . [ 108 ]


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. [ 109 ]


It has been theorized that antistreptococcal medications may improve guttate and chronic plaque psoriasis; however, limited studies do not show that antibiotics are effective. [ 110 ]


Limited evidence suggests  removal of the tonsils  may benefit people with chronic plaque psoriasis, guttate psoriasis, and palmoplantar pustulosis. [ 111 ] [ 112 ]


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). [ 113 ]  A low-calorie diet appears to reduce the severity of psoriasis. [ 43 ]  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 caffeine consumption (including from coffee, black tea, mate, and dark chocolate) remains to be determined. [ 114 ]


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. [ 115 ]


There is a higher rate of  celiac disease  among people with psoriasis. [ 114 ] [ 116 ]  When adopting a  gluten-free diet , disease severity generally decreases in people with celiac disease and those with  anti-gliadin antibodies . [ 113 ] [ 117 ] [ 118 ]


Most people with psoriasis experience nothing more than mild skin lesions that can be treated effectively with topical therapies. [ 79 ]  Depending on the severity and location of outbreaks, people may experience significant physical discomfort and some disability, affecting the person's quality of life. [ 34 ]  Itching and pain can interfere with basic functions, such as self-care and sleep. [ 52 ]  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. [ 52 ]  Plaques on the scalp can be particularly embarrassing, as flaky plaque in the hair can be mistaken for  dandruff . [ 119 ]


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. [ 3 ]  People with psoriasis often feel prejudiced against due to the commonly held incorrect belief that psoriasis is contagious. [ 52 ]  Psychological distress can lead to significant  depression  and  social isolation ; a high rate of  thoughts about suicide  has been associated with psoriasis. [ 21 ]  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. [ 120 ]  Children with psoriasis may encounter  bullying . [ 121 ]


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. [ 122 ]


Psoriasis has been associated with  obesity [ 3 ]  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. [ 123 ]  Severe psoriasis may be even more strongly associated with the development of diabetes than mild psoriasis. [ 123 ]  Younger people with psoriasis may also be at increased risk for developing diabetes. [ 122 ] [ 124 ]  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. [ 42 ] [ 122 ]


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 [ when? ]  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 . [ 124 ] [ 125 ]  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. [ 126 ]  There may be a slightly increased risk of stroke associated with psoriasis, especially in severe cases. [ 42 ] [ 127 ]  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. [ 128 ]  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 . [ 128 ]  Compared to individuals without psoriasis, those affected by psoriasis are more likely to satisfy the criteria for  metabolic syndrome . [ 16 ] [ 126 ]


The rates of  Crohn's disease  and  ulcerative colitis  are increased when compared with the general population, by a factor of 3.8 and 7.5 respectively. [ 3 ]  People with psoriasis also have a higher risk of  celiac disease . [ 114 ] [ 118 ]  Few studies have evaluated the association of  multiple sclerosis  with psoriasis, and the relationship has been questioned. [ 3 ] [ 129 ]  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. [ 42 ]  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 . [ 42 ]  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%. [ 42 ]  There is no increased risk of  melanoma  associated with psoriasis. [ 42 ]  People with psoriasis have a higher risk of developing cancer. [ 130 ]


Psoriasis is estimated to affect 2–4% of the population of the western world. [ 7 ]  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. [ 7 ]  Psoriasis is about five times more common in people of European descent than in people of Asian descent, [ 131 ]  more common in countries farther from the  equator , [ 49 ]  relatively uncommon in African Americans, and extremely uncommon in Native Americans. [ 50 ]  Psoriasis has been estimated to affect about 6.7   million Americans. [ 5 ]


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. [ 5 ]  Approximately one-third of people with psoriasis report being diagnosed before age 20. [ 132 ]  Psoriasis affects both  sexes  equally. [ 63 ]


People with  inflammatory bowel disease  such as Crohn's disease or ulcerative colitis are at an increased risk of developing psoriasis. [ 49 ]


Scholars believe psoriasis to have been included among the various skin conditions called  tzaraath  (translated as leprosy) in the  Hebrew Bible . [ 133 ]  The person was deemed "impure" (see  tumah and taharah ) during their affected phase and is ultimately treated by the  kohen . [ 134 ]  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. [ 134 ]  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 . [ 135 ]


Psoriasis is thought to have first been described in  Ancient Rome  by  Cornelius Celsus . [ 136 ]  The British dermatologist  Thomas Bateman  described a possible link between psoriasis and arthritic symptoms in 1813. [ 136 ]  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. [ 134 ]   Mercury  was also used for psoriasis treatment during this time. [ 134 ]   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. [ 134 ]  Coal tars were widely used with ultraviolet light irradiation as a topical treatment approach in the early 1900s. [ 134 ] [ 137 ]  During the same time, psoriatic arthritis cases were treated with intravenously administered gold preparations in the same manner as  rheumatoid arthritis . [ 137 ]


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. [ 138 ]  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.


The annual cost of 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. [ 139 ]


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. [ 140 ]


Many novel medications being researched during the 2010s target the  Th17 / IL-23  axis, [ 140 ]  particularly  IL-23p19  inhibitors, as IL-23p19 is present in increased concentrations in psoriasis skin lesions while contributing less to protection against opportunistic infections. [ 141 ]  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. [ 141 ]  Another avenue of research has focused on the use of  vascular endothelial growth factor inhibitors  to treat psoriasis. [ 65 ]  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. [ 140 ] [ 141 ]  These agents have potentially severe side-effects due to their immunosuppressive mechanisms. [ 141 ]


Purple glove syndrome  (PGS) is a poorly understood  skin disease  in which the extremities become  swollen , discoloured and painful. [ 1 ]  PGS is potentially serious and may require  amputation .  PGS is most common among  elderly  patients and those receiving multiple large  intravenous  doses of the  epilepsy  drug  phenytoin . [ 2 ]  Compartment syndrome is a complication of PGS.


Purple glove syndrome is caused by the intravenous anticonvulsant phenytoin. [ 3 ]  This medication has many already established neurological side effects. However, glove syndrome is a rare, with prevalence ranging from 1.7% to 5.9%, but has very serious adverse effect that may lead to limb amputations. This may occur due to the administration of phenytoin with or without extravasation. The defining characteristic is a purplish to black discoloration of the extremity followed by  peripheral edema  and pain distal to the site of infusion. Onset is generally seen within the first few hours of administration. The true pathology of purple glove syndrome is not fully elucidated, however it is believed to be due to the crystallization of phenytoin within the blood and  extravasates  into the surrounding interstitium. Another mechanism may be due to the disruption of endothelial transcellular junctions followed by leaking of phenytoin into the surround soft tissues.


A diagnosis is usually made if symptoms of PSG appear after a dosage of phenytoin, especially if symptoms such as edema are near the injection site. [ 1 ]


Doctors recommend discontinuing the use of phenytoin. The application of heat can help to relieve pain. Limb elevation, compression, and massage are also often used to relieve symptoms. Oral phenytoin can also result in development of purple glove syndrome. [ 4 ]


As of April 2012 [update] , multiple press sources reported an outbreak of an unidentified  skin disease  in the  Ba Tơ District  of  Quảng Ngãi Province ,  Vietnam . The disease is reported to begin as a skin rash, and in numerous cases appears to have led to the death of the affected individual through  organ failure . [ 1 ] [ 2 ]  As of 21 April 2012 [update] , the disease was reported to have affected 170 people, and killed 19. [ 1 ]


The Associated Press reported that Vietnam has asked for assistance from the  World Health Organization . [ 3 ]


Another, separate unknown skin disease was reported from Quảng Ngãi's  Sơn Hà District  in early May 2012. [ 4 ]


Poisonous  heavy metals  in the soil or  toxic mould  on rice have been considered the most likely causes so far. [ 5 ]


Another outbreak of the same disease in the Quảng Ngãi area was reported in March 2013. [ 6 ]


This  Vietnam -related article is a  stub . You can help Wikipedia by  expanding it .


Many conditions of or affecting the human integumentary system have associated features that may be found by performing an x-ray or CT scan of the affected person.


Rosacea  is a  long-term   skin condition  that typically affects the face. [ 2 ] [ 3 ]  It results in  redness ,  pimples ,  swelling , and  small and superficial dilated blood vessels . [ 2 ]  Often, the nose, cheeks, forehead, and chin are most involved. [ 3 ]  A red, enlarged nose may occur in severe disease, a condition known as  rhinophyma . [ 3 ]


The cause of rosacea is unknown. [ 2 ]  Risk factors are believed to include a family history of the condition. [ 3 ]  Factors that may potentially worsen the condition include heat, exercise, sunlight, cold, spicy food, alcohol,  menopause ,  psychological stress , or  steroid cream  on the face. [ 3 ]  Diagnosis is based on symptoms. [ 2 ]


While not curable, treatment usually improves symptoms. [ 3 ]  Treatment is typically with  metronidazole ,  doxycycline ,   minocycline , or  tetracycline . [ 4 ]  When the eyes are affected,  azithromycin  eye drops may help. [ 5 ]  Other treatments with tentative benefit include  brimonidine  cream,  ivermectin  cream, and  isotretinoin . [ 4 ]   Dermabrasion  or  laser surgery  may also be used. [ 3 ]  The use of  sunscreen  is typically recommended. [ 3 ]


Rosacea affects between 1% and 10% of people. [ 2 ]  Those affected are most often 30 to 50 years old and female. [ 2 ]  Fair-skinned people seem to be more commonly affected. [ 6 ]   The condition was described in  The Canterbury Tales  in the 1300s, and possibly as early as the 200s BC by  Theocritus . [ 7 ] [ 8 ]


Rosacea typically begins with  reddening (flushing)  of the skin in symmetrical patches near the center of the face. [ 10 ]  Common signs can depend on age and sex:  flushing  and  red swollen patches  are common in the young,  small and visible dilated blood vessels  in older individuals, and  swelling of the nose  is common in men. [ 10 ]  Other signs include lumps on the skin ( papules  or  pustules ) and  swelling  of the face. [ 10 ]  Many people experience stinging or burning pain and rarely itching. [ 10 ]


Skin problems tend to be aggravated by particular trigger factors, that differ for different people. Common triggers are  ultraviolet  light, heat, cold, or certain foods or beverages. [ 10 ]


Erythematotelangiectatic rosacea [ 11 ]  rosacea (also known as "vascular rosacea" [ 11 ] ) is characterized by prominent history of prolonged (over 10 minutes)  flushing  reaction to various  stimuli , such as  emotional stress , hot drinks, alcohol, spicy foods,  exercise , cold or hot weather, or hot  baths  and  showers . [ 12 ]


In glandular rosacea, men with thick sebaceous skin predominate, a disease in which the papules are  edematous , and the pustules are often 0.5 to 1.0 cm in size, with nodulocystic lesions often present. [ 12 ]


The exact cause of rosacea is unknown. [ 2 ]  Triggers that cause episodes of flushing and blushing play a part in its development. Exposure to temperature extremes, strenuous exercise, heat from sunlight, severe  sunburn , stress, anxiety, cold wind, and moving to a warm or hot environment from a cold one, such as heated shops and offices during the winter, can each cause the face to become flushed. [ 2 ]  Certain foods and drinks can also trigger flushing, such as alcohol, foods and beverages containing  caffeine  (especially hot tea and coffee), foods high in  histamines , and  spicy foods . [ 13 ]


Medications and topical irritants have also been known to trigger rosacea flares. Some  acne  and wrinkle treatments reported to cause rosacea include  microdermabrasion  and  chemical peels , as well as high dosages of  isotretinoin ,  benzoyl peroxide , and  tretinoin .


Steroid -induced rosacea is caused by the use of topical  steroids . [ 14 ]  These steroids are often prescribed for  seborrheic dermatitis . Dosage should be slowly decreased and not immediately stopped to avoid a flare-up.


In 2007,  Richard Gallo  and colleagues noticed that patients with rosacea had high levels of   cathelicidin , an  antimicrobial peptide , [ 15 ]  and elevated levels of  stratum corneum  tryptic  enzymes  ( SCTEs ).  Antibiotics  have been used in the past to treat rosacea, but they may only work because they inhibit some SCTEs. [ 15 ]


Studies of rosacea and  Demodex  mites have revealed that some people with rosacea have increased numbers of the mite, [ 13 ]  especially those with steroid-induced rosacea.  Demodex folliculitis  (demodicidosis, also known as "mange" in animals) is a condition that may have a "rosacea-like" appearance. [ 16 ]


A 2007,  National Rosacea Society -funded study demonstrated that  Demodex folliculorum  mites may be a cause or exacerbating factor in rosacea. [ 17 ]  The researchers identified  Bacillus oleronius  as a distinct bacterium associated with  Demodex  mites. When analyzing blood samples using a peripheral blood mononuclear cell proliferation assay, they discovered that  B. oleronius  stimulated an immune system response in 79 percent of 22 patients with subtype 2 (papulopustular) rosacea, compared with only 29% of 17 subjects without the disorder. They concluded, "The immune response results in inflammation, as evident in the papules (bumps) and  pustules  (pimples) of subtype 2 rosacea. This suggests that the  B. oleronius  bacteria found in the mites could be responsible for the inflammation associated with the condition." [ 17 ]


Small intestinal bacterial overgrowth  (SIBO) was demonstrated to have greater prevalence in rosacea patients and treating it with locally acting antibiotics led to rosacea lesion improvement in two studies. Conversely in rosacea patients who were SIBO negative, antibiotic therapy had no effect. [ 18 ]  The effectiveness of treating SIBO in rosacea patients may suggest that gut bacteria play a role in the pathogenesis of rosacea lesions.


Most people with rosacea have only mild redness and are never formally diagnosed or treated.  No test for rosacea is known. In many cases, simple visual inspection by a trained health-care professional is sufficient for diagnosis.  In other cases, particularly when pimples or redness on less-common parts of the face is present, a trial of common treatments is useful for confirming a suspected diagnosis. The disorder can be confused or co-exist with  acne vulgaris  or  seborrheic dermatitis .  The presence of a rash on the scalp or ears suggests a different or co-existing diagnosis because rosacea is primarily a facial diagnosis, although it may occasionally appear in these other areas.


Four rosacea subtypes exist, [ 20 ]  and a patient may have more than one subtype: [ 21 ] : 176


Variants of rosacea include: [ 26 ] : 689


The type of rosacea that a person has will indicate the choice of treatment. [ 27 ]  Mild cases are often not treated at all, or are simply covered up with  normal cosmetics .


Therapy for the treatment of rosacea is not curative, and is best measured in terms of reduction in the amount of facial redness and inflammatory lesions, a decrease in the number, duration, and intensity of flares, and concomitant symptoms of itching, burning, and tenderness. The two primary modalities of rosacea treatment are topical and oral antibiotic agents. [ 28 ]  Laser therapy has also been classified as a form of treatment. [ 28 ]  While medications often produce a temporary remission of redness within a few weeks, the redness typically returns shortly after treatment is suspended.  Long-term treatment, usually 1–2 years, may result in permanent control of the condition for some patients. [ 28 ] [ 29 ]  Lifelong treatment is often necessary, although some cases resolve after a while and go into a permanent remission. [ 29 ]   Other cases, if left untreated, worsen over time. [ 30 ]  Some people have also reported better results after changing diet. This is not confirmed by medical studies, even though some studies relate the histamine production to outbreak of rosacea. [ 31 ]


Certain behavioral changes may improve the symptoms of rosacea or help to prevent exacerbations. Keeping a symptoms diary to document potential symptom triggers and avoiding those triggers is recommended. [ 25 ]  Common exacerbating triggers include ultraviolet light and irritant cosmetics, therefore it is recommended that those with rosacea wear  sunscreen  (with a sun factor protection (SPF) of 30 or greater) and avoid cosmetics. [ 25 ]  If using cosmetics or makeup is desired, then oil free foundation and concealer should be used. [ 25 ]  Skin astringents, products that can dry the skin and impair the skin barrier, including products with alcohol, menthol, peppermint, camphor, or eucalyptus oil, should generally be avoided. People should avoid using exfoliating skin scrubs, cosmetics or soaps containing  sodium laureth sulfate , or waterproof makeup to the affected area as these products can compromise the skin barrier protection and be difficult to remove. [ 25 ]  Using soap-free cleansers and non-oily moisturizers are preferred if used on the affected area. Many skin care products have been specifically formulated for those with sensitive skin or for those with conditions such as rosacea. [ 25 ]  Ocular rosacea may be treated with daily gentle eyelid washing using warm water, and artificial tears to lubricate the eye. [ 25 ]


Managing pre-trigger events such as prolonged exposure to cool environments can directly influence warm-room flushing. [ 32 ]


Medications with good evidence include topical  metronidazole , [ 33 ]   ivermectin  and  azelaic acid . [ 34 ]  Good evidence medications taken by mouth include  brimonidine , and  doxycycline  and  isotretinoin . [ 34 ]  Lesser evidence supports  tetracycline  by mouth. [ 34 ]  Isotretinoin and tetracycline antibiotics, which may be used in more severe cases of inflammatory rosacea, are absolutely contraindicated in women who are pregnant, may become pregnant or lactating as they are highly  teratogenic  (associated with birth defects). Contraception is required for women of child bearing age who are using these medications. [ 25 ]


Metronidazole is thought to act through anti-inflammatory mechanisms, while azelaic acid is thought to decrease cathelicidin production. Oral antibiotics of the  tetracycline  class such as doxycycline, minocycline, and  oxytetracycline  are also commonly used and thought to reduce papulopustular lesions through anti-inflammatory actions rather than through their antibacterial capabilities. [ 13 ]


Topical minocycline applied as a foam is a newer treatment option for rosacea that the FDA has approved. Minocycline shows a targeted approach for managing inflammatory lesions of rosacea while minimizing systemic side effects commonly associated with oral antibiotic use. It is available in foam formulation and is applied to the affected areas once daily. Minocycline belongs to the tetracycline family of antibiotics and exhibits antimicrobial properties and anti-inflammatory activity, similar to other members of this class, such as doxycycline. Topical minocycline reduces inflammatory lesions associated with rosacea; however, rare adverse events such as folliculitis have been reported. [ 33 ]


Topical metronidazole is a commonly used treatment for rosacea; it is available in various formulations such as creams, gels, or lotions and applied to clean, dry skin once or twice daily. Topical metronidazole has been shown to effectively reduce inflammatory lesions and perilesional erythema associated with rosacea by inhibiting both microbial growth and pro-inflammatory mediators generated by neutrophils. Benefits of topical metronidazole include its effectiveness in reducing symptoms, extensive clinical experience supporting its use, and generally good tolerability with minimal systemic side effects; still, some patients may experience mild local irritation upon initial use, and it may have limited impact on persistent facial redness (erythema). [ 33 ]


Topical azelaic acid is available in gel or cream formulations; it exerts its effects by reducing inflammation through its activity on the cathelicidin pathway, which is upregulated in rosacea-affected skin; it also reduces inflammatory lesions and improves overall symptoms of rosacea; it has been well-studied and shown to be effective in clinical trials; still, some patients may experience mild local irritation during the first few weeks of use. [ 33 ]


Using  alpha-hydroxy acid  peels may help relieve redness caused by irritation, and reduce papules and pustules associated with rosacea. [ 35 ]


Oral  Beta-blockers  are often used for those with flushing due to rosacea. These include  nadolol ,  propranolol  or  carvedilol . The possible adverse reactions of the oral beta-blockers include  low blood pressure ,  low heart rate  or dizziness. [ 25 ]  The oral  α-2 adrenergic receptor agonist   clonidine  can also be used for flushing symptoms. [ 25 ]  The flushing and blushing that typically accompany rosacea may also be treated with the topical application of  alpha agonists  such as brimonidine which has vasoconstrictor activity and achieves maximal symptom improvement 3–6 hours after application, other topicals used for flushing or erythema include  oxymetazoline  or  xylometazoline . [ 13 ]


Topical ivermectin is a treatment option for rosacea that targets Demodex mites, which are associated with inflammation in the skin of patients with rosacea; the cream is applied once daily to clean, dry skin. Topical ivermectin has been shown to reduce Demodex mite density and improve cutaneous inflammatory markers in clinical studies; overall, it decreases Demodex mite density and improves the symptoms of inflammation associated with rosacea; however, some patients may experience transient burning or itching upon application. Topical ivermectin offers a targeted approach for managing rosacea by addressing the role of Demodex mites in the disease process. [ 33 ]  A review found that ivermectin was more effective than alternatives for treatment of papulopustular acne rosacea. [ 36 ] [ 37 ]  An ivermectin cream has been approved by the  FDA , as well as in Europe, for the treatment of inflammatory  lesions  of rosacea. The treatment is based upon the hypothesis that parasitic mites of the genus  Demodex  play a role in rosacea. [ 38 ]  In a clinical study, ivermectin reduced lesions by 83% over 4 months, as compared to 74% under a  metronidazole  standard therapy. [ 39 ]   Quassia amara extract at 4% demonstrated to have clinical efficacy for rosacea. [ 40 ]  When compared to metronidazole 0.75% as usual care in a randomized, double-blinded clinical trial, Quassia amara extract at 4% demonstrated earlier onset of action, including improvement in telangiectasia, flushing, and papules. Quassia amara showed a sustained reduction of symptoms at 42 days of treatment. [ 41 ]


Cyclosporin  eye drops have been shown to reduce symptoms in those with ocular rosacea. Cyclosporin should not be used in those with an active ocular infection. [ 25 ]  Other options include topical metronidazole cream or topical  fusidic acid  applied to the eyelids, or oral doxycycline in more severe cases of ocular rosacea. If papules and pustules persist, then sometimes isotretinoin can be prescribed. [ 42 ]


Systemic doxycycline modified-release capsules are commonly used for the treatment of rosacea. The capsules are taken orally once daily, usually in a low dose, to achieve anti-inflammatory effects. Doxycycline acts by inhibiting inflammation and reducing the production of reactive oxygen species associated with rosacea symptoms. The benefits of systemic doxycycline include its effectiveness in reducing inflammatory lesions, improving erythema, and controlling symptoms related to ocular involvement in rosacea patients; it is also well-tolerated at lower doses compared to traditional higher-dose regimens used for other indications. However, potential cons include gastrointestinal side effects such as nausea or abdominal pain, photosensitivity reactions that require sun protection measures during treatment, and rare instances of antibiotic-associated diarrhea or bacterial resistance development with long-term use. [ 33 ]


Encapsulated benzoyl peroxide (E-BPO) cream, a newly FDA-approved topical agent for inflammatory lesions of rosacea, utilizes porous silica microcapsule technology to slow the absorption of benzoyl peroxide and diminish potential irritation. [ 33 ]


Evidence for the use of laser and intense pulsed-light therapy in rosacea is poor. [ 43 ]


The highly visible nature of rosacea symptoms are often psychologically challenging for those affected. People with rosacea can experience issues with self-esteem, socializing, and changes to their thoughts, feelings, and coping mechanisms. [ 10 ]


Rosacea affects around 5% of people worldwide. [ 10 ]  Incidence varies by ethnicity, and is particularly prevalent in those of  Celtic  heritage. [ 10 ]  Men and women are equally likely to develop rosacea. [ 10 ]


Sclerodactyly  is a localized  thickening and tightness  of the  skin  of the  fingers  or  toes  that yields a characteristic claw-like appearance and spindle shape of the affected  digits , and renders them immobile or of limited mobility. [ 1 ] [ 2 ]   The thickened, discolored patches of skin are called  morphea , and may involve  connective tissue  below the skin, as well as  muscle  and other tissues. [ 3 ]  Sclerodactyly is often preceded by months or even years by  Raynaud's phenomenon  when it is part of  systemic scleroderma . [ citation needed ]


The term "sclerodactyly" comes from  Greek    skleros  'hard' and   daktylos  'digit'.


It is generally associated with systemic scleroderma and  mixed connective tissue disease , and  auto-immune disorders .


Sclerodactyly is one component of the  limited cutaneous form of systemic sclerosis  (lcSSc), also known as CREST syndrome (CREST is an acronym that stands for  calcinosis , Raynaud's phenomenon,  esophageal dysmotility , sclerodactyly, and  telangiectasia .) [ 4 ]  Sclerodactyly is also one component of  Huriez Syndrome , along with palmoplantar keratoderma and skin cancer. [ 5 ]  Sclerodactyly sometimes arises as a complication of the microvascular changes seen in  diabetes mellitus , and is in this case referred to as diabetic sclerodactyly. [ 6 ] [ 7 ] [ 8 ]


Treatment of sclerodactyly is by physical therapy, phototherapy, surgery, topical corticosteroids or vitamin D analogues, and systemic immunosuppressive drugs when the condition is part of systemic scleroderma [ citation needed ] . Localized treatment won't halt systemic disease, but can restore function and cosmetic aspects of the affected digits. The mild to moderate proximal interphalangeal (PIP) joint flexion and extension contractures and stiff distal interphalangeal (DIP) joints in slight flexion often seen in sclerodactyly can be addressed somewhat with physical therapy. [ 9 ]  In a few cases when immune involvement isn't apparent (in these cases environmental causes are suspected), the condition may gradually clear up by itself If the trigger is avoided [ citation needed ] . In other cases, early treatment while the disease is in the inflammatory stage is much more likely to be successful than on established lesions [ citation needed ] .


A  skin infection  is an  infection  of the  skin  in humans and other animals, that can also affect the associated  soft tissues  such as  loose connective tissue  and  mucous membranes . [ citation needed ]  They comprise a category of infections termed  skin and skin structure infections  (SSSIs), or skin and soft tissue infections (SSTIs), [ 1 ]  and acute bacterial SSSIs (ABSSSIs). [ 2 ]  They are distinguished from  dermatitis  ( inflammation  of the skin), [ 3 ] [ 4 ]  although skin infections can result in skin inflammation. [ 5 ]


Bacterial skin infections affected about 155 million people and cellulitis occurred in about 600 million people in 2013. [ 6 ]  Bacterial skin infections include:


Fungal skin infections may present as either a superficial or deep  infection  of the skin, hair, and/or nails.  Mycetoma  are a broad group of fungal infections that characteristically originate in the skin and subcutaneous tissues of the foot. [ 18 ]  If not treated appropriately and in a timely fashion mycetoma infections can extend to deeper tissues like bones and joints causing osteomyelitis. [ 19 ]  Extensive osteomyelitis can necessitate surgical bone resections and even lower limb amputation. [ 19 ]
As of 2010, they affect about one billion people globally. [ 20 ]  Some examples of common fungal skin infections include:


Parasitic infestations of the skin are caused by several  phyla  of organisms, including  Annelida ,  Arthropoda ,  Bryozoa ,  Chordata ,  Cnidaria ,  Cyanobacteria ,  Echinodermata ,  Nemathelminthes ,  Platyhelminthes , and  Protozoa . [ 28 ]


Virus-related cutaneous conditions caused by these obligate  intracellular  agents derive from both  DNA  and  RNA  viruses. [ 29 ]  Some examples of viral skin infections include:


Maceration  is defined as the softening and breaking down of  skin  resulting from prolonged exposure to moisture. It was first described by  Jean-Martin Charcot  in 1877. [ 1 ] [ 2 ]  Maceration is caused by excessive amounts of fluid remaining in contact with the skin or the surface of a wound for extended periods.


Maceration often occurs with the application of a bandage to a wound, regardless of its mildness or severity, particularly if the bandage prevents water from evaporating from the surface of the skin. This occurs because the skin under the bandage becomes wet due to  perspiration ,  urine  or other bodily fluids, or contact with other liquids. The excess moisture is sometimes called hyperhydration.


One may also notice maceration after wearing non-breathable plastic or latex rubber gloves, which trap moisture against the skin.


Wrinkles are the first sign that the skin is over-hydrated. In addition, macerated skin becomes extremely soft and takes on a whitish appearance. However, this white skin should not be confused with the pale, whitish appearance of the new  epithelial tissue  in a healing wound.


Although most maceration clears up quickly once the skin is exposed to fresh air and allowed to dry, sometimes skin that experiences long periods of maceration is vulnerable to  fungal  and  bacterial infection . As opportunistic organisms affect the area, it may become itchy or develop a foul odour.


Stasis papillomatosis  is a disease characterized by chronic congestion of the extremities, with  blood circulation  interrupted in a specific area of the body. [ 1 ]  A consequence of this congestion and inflammation is long-term  lymphatic  obstruction ( lymphedema ). [ 2 ]  It is also typically characterized by the appearance of numerous  papules . [ 3 ]  Injuries can range from small to large plates composed of brown or pink, smooth or  hyperkeratotic  papules. [ 4 ]  The most typical areas where injuries occur are the back of the feet, the toes, the legs, and the area around a  venous ulcer  formed in the extremities, although the latter is the rarest of all. [ 2 ]  These injuries include  pachydermia  (thickening of the skin), lymphedema (swelling due to  lymph vessel  blockage),  lymphomastic verrucosis  and  elephantosis verrucosa . The disease can be either localized or generalized; the localized form makes up 78% of cases. [ 2 ]  Treatment includes surgical and pharmaceutical intervention; indications for partial removal include advanced  fibrotic lymphedema  and  elephantiasis . [ 5 ]  Despite the existence of these treatments, chronic venous edema, which is a derivation of stasis papillomatosis, is only partially reversible. The skin is also affected and its partial removal may mean that the skin and the subcutaneous tissue are excised. [ 6 ]  A side effect of the procedure is the destruction of existing cutaneous lymphatic vessels. It also risks papillomatosis, skin necrosis and edema exacerbation. [ 7 ]


All  etiologies  lead to local dermal lymphostasis pathogenesis. A maximum variation was observed after the resection of block subcutaneous tissue in patients with congenital lymphedema. Signals that the current condition are different, either in the dermis or in the subcutaneous area. [ 8 ]


Chronic inflammation can cause long term lymphatic obstruction. [ 4 ]  Typically, patients have disorders that present local nodes, primary lymphedema and chronic venous insufficiency. Erysipelas and trauma are major risk factors. Lymphatic edema can be developed in many acral cases accompanied by a thickening of the folds of the skin, hyperkeratosis and papillomatosis. [ 2 ]  Chronic venous edema is only partially reversible and soon becomes hard, especially confirming tenderness. All structures of the skin are affected. Dilated dermal lymphatic vessels with consequent superior organization and fibrosis result in papillomatosis. As dermal lymphatic stasis progreses, these skin changes become more marked and known as elephantiasis. Occasionally, tissue fibrosis and thickening may become so marked in the later stages of lymphedema that pitting is absent. Recurrent cellulitis, erysipelas and dermato-LAM-adenitis are complications of chronic lymphedema. [ 7 ]


The reason for its occurrence is unknown. Investigations have suspected that obesity and preceding psoriatic lesions cause local lymphatic disturbances, followed by the development of stasis papillomatosis. [ 8 ]  On the other hand, genetic or environmental factors may play a role. Some investigators have speculated that it represents an allergic response to an epidermal protein antigen created through increased hydrostatic pressure, whereas others believe that the skin has been compromised and is more susceptible to irritation and trauma. [ 5 ]


Age is an important factor because as some people get older the veins which carry blood from the legs back to the heart do not work as well as they use to. This causes fluid to settle in the lower legs. [ 9 ]


The most important cause of this condition is insufficient lymphatic drainage, causing soft tissue swelling due to fluid accumulation. Obstruction of lymphatic tissue causes increased intravascular tissue protein; this will increase the production of fibroblasts and mast cells. [ 3 ] [ 6 ]  Lymphatic obstruction due to any cause can increase the amount of proteins in the intravascular tissue, either by root osmotic pressure or because it absorbs a little liquid. The further roteins increase the vascular fluid, fibroblasts and promote the ploriferation of mast cells which produce the clinical symptoms of nonpitting edema. The epidermis may be hyperkeratotic and warty and this predisposes to tissue cracks and allows secondary infection. [ 4 ]


Stasis Papillomatosis is similar to AGEP (Acute generalized exanthematous pustulosis) from pustular psoriasis; criteria for histopathologic distinction have been proposed: papillary edema, vasculitis, exocytosis of eosinophils and single-cell necrosis of keratinocytes in AGEP and acanthosis and papillomatosis in pustular psoriasis. [ 2 ]


An example that illustrates the difference between SP and Stasis Papillomatosis and the histology diagnosis is:  "a markedly obese, 41-year-old Japanese man who had suffered from psoriasis vulgaris for several years visited hospital with elephantiasis-like swelling of his lower legs of three months' duration. His right lower leg showed marked papillomatosis with thick scales, and the left lower leg was eroded and papillomatous. [ 6 ]  Although direct lymphography of his lower extremities showed no abnormality, indirect lymphography revealed local lymphatic damage in the involved skin". [ 4 ]  Histological examination showed hyperkeratosis, marked papillomatosis, proliferation of capillaries in the upper dermis, and lymphectasia in the lower dermis. It was suspected that obesity and the preceding psoriatic lesions caused local lymphatic disturbances, followed by the development of stasis papillomatosis. [ 7 ]


This disease is caused by problems in the circulatory system; thus, the legs should be elevated as much as possible to help the return of the blood. At night it is advisable to sleep with a pillow under the lower legs. [ 7 ]  In the evening, it is not unusual for legs to be swollen. The volume of the lower leg can increase to up to 100ml after a long working day or up to 200ml after a long-haul flight without moving. [ 3 ] [ 4 ]


In the example of the 41-year-old Japanese man the lesions were much improved by washing and topical use of corticosteroids for two months, also oral antibiotics like cephalexin are used if cellulitis is present. Moist exudative inflammation and moist ulcers respond to tepid wet compresses of Burow's solution or just saline or water for 30 to 60 minutes several times a day. [ 10 ]   But in worse cases, edema that does not disappear spontaneously within a few hours or after a walk, is described as pathological, so it needs to have a special treatment. It is very important to say that Papillamitosis, bilateral and marked edema with few symptoms are mostly caused by the systemic circulation (heart, kidneys, liver). [ 4 ]


Papillamitosis is associated with symptoms and/or clinical signs such as dilated superficial veins, varicose veins and changes in the skin. [ 4 ]  Edema and its complication Papillamitosis are only partially reversible and soon becomes hard, which is mainly confirmed on palpation. All skin structures are affected and this is characterized by the term. Lymphoedema may develop in many cases accompanied by acral thickening of the skin folds, hyperkeratosis and papillomatosis. [ 4 ] [ 6 ]


Steroid-induced skin atrophy  is thinning of the skin as a result of prolonged exposure to  topical steroids . In people with  psoriasis  using topical steroids it occurs in up to 5% of people after a year of use. [ 5 ]  Intermittent use of topical steroids for  atopic dermatitis  is safe and does not cause skin thinning. [ 6 ] [ 7 ] [ 8 ]


Skin atrophy can occur with both prescription and over the counter steroids creams. [ 9 ]  Low doses of  prednisone  by mouth can also result in skin atrophy.


It can also present with  telangiectasia , easy bruising,  purpura , and  striae . Occlusive dressings and fluorinated steroids both increase the likelihood of developing atrophy. [ 10 ]


In general, use a potent preparation short term and weaker preparation for maintenance between flare-ups. While there is no proven best benefit-to-risk ratio, [ 11 ]  if prolonged use of a topical steroid on a skin surface is required, a pulse therapy should be undertaken.


Pulse therapy refers to the application of a corticosteroid for 2 or 3 consecutive days each week or two. This is useful for maintaining control of chronic diseases. Generally a milder topical steroid or non-steroid treatment is used on the in-between days. [ 12 ]


For treating  atopic dermatitis , newer (second generation) corticosteroids, such as  fluticasone propionate  and  mometasone furoate , are more effective and safer than older ones. They are also generally safe and do not cause skin thinning when used in intermittently to treat atopic dermatitis flare-ups. They are also safe when used twice a week for preventing flares (also known as weekend treatment). [ 6 ] [ 7 ] [ 8 ]  Applying once daily is enough as it is as effective as twice or more daily application. [ 13 ]


Strong steroids should be avoided on sensitive sites such as the face, groin and armpits. Even the application of weaker or safer steroids should be limited to less than two weeks on those sites.


The obvious priority is immediate discontinuation of any further topical corticosteroid use. Protection and support of the impaired skin barrier is another priority. Eliminating harsh skin regimens or products will be necessary to minimize potential for further purpura or trauma, skin sensitivity, and potential infection. Steroid-induced skin atrophy [ 14 ] [ 15 ]  is often permanent, though if caught soon enough and the topical corticosteroid discontinued in time, the degree of damage may be arrested or slightly improve. However, while the accompanying  telangiectasias  may improve marginally, the  stretch marks  are permanent and irreversible. [ 16 ]


Tegumental angiomyxoma-neurothekeoma  ( TAN syndrome ) [ 1 ]  is a  syndrome , an  acronym , and  eponym [ citation needed ]  proposed by  Malaysian   ophthalmologist  of Chinese Descent, Tan Aik Kah (b. June 1975). [ 1 ]  Angiomyxomas are associated with  LAMB  (lentigines, atrial myxomas, muco-cutaneous myxomas, and blue naevi) syndrome, [ 2 ]  NAME (nevi, atrial myxoma, myxoid neurofibromas, and ephelides) [ 3 ]  syndrome and  Carney syndrome  (atrial, cutaneous and mammary myxomas, lentigines, blue naevi, endocrine disorders and  testicular tumours ). [ 4 ]


TAN syndrome is characterized by multiple superficial  angiomyxoma  and  neurothekeoma  confined only to the skin (tegument). [ 1 ]   TAN syndrome  may be used to describe myxomas confined to the skin without visceral involvement. [ citation needed ]


Tan et al. reported a 10-year-old girl with multiple superficial angiomyxoma associated with neurothekeoma palpebrae. [ 1 ]  There was no evidence of visceral involvement. The lesions were excised with no recurrence during follow up. [ 1 ]


Circulating auto-antibodies in the human body can target normal parts of the skin leading to disease.  This is a list of antigens in the skin that may become targets of circulating auto-antibodies leading to the various types of  pemphigoid .


Of note, there are also several other diseases that are caused by auto-antibodies that target the same anatomic area of the skin which is termed the  basement membrane zone .  These diseases include:


Circulating auto-antibodies in the human body can target normal parts of the skin leading to disease.  This is a list of antigens in the skin that may become targets of circulating auto-antibodies leading to the various types of  pemphigus .


Tetter  refers to any skin condition characterized by reddish  vesicular  eruptions and intense  itching . Common diseases called tetter include:


Topical steroid withdrawal , also known as  red burning skin  and  steroid dermatitis , has been reported in people who apply  topical steroids  for 2 weeks or longer and then discontinue use. [ 4 ] [ 5 ] [ 2 ] [ 1 ]  Symptoms affect the skin and include redness, a burning sensation, and itchiness, [ 2 ]  which may then be followed by peeling. [ 2 ]


This condition generally requires the daily application of a topical steroid for more than 2 weeks but sometimes can occur with even less steroid use. It appears to be a specific adverse effect of topical corticosteroid use. [ 6 ]  People with  atopic dermatitis  are most at risk. [ 3 ]


Treatment involves discontinuing the use of topical steroids, [ 2 ]  either gradually or suddenly. [ 2 ]  Counselling and cold compresses may also help. [ 2 ]  Thousands of people congregate in online communities to support one another throughout the healing process, and cases have been reported in both adults and children. [ 2 ] [ 1 ]  It was first described in 1979. [ 3 ]


Topical steroid addiction (TSA) is characterised by uncontrollable, spreading dermatitis and worsening skin  inflammation , which requires a stronger topical steroid to get the same result as the first prescription. This cycle is known as steroid addiction syndrome. [ 7 ]  When topical steroid medication is stopped, the skin experiences redness, burning, a deep and uncontrollable itch, scabs, hot skin, swelling, stinging, hives and/or oozing for a length of time. This is also called 'red skin syndrome' or 'topical steroid withdrawal' (TSW). After the  withdrawal  period is over, the  atopic dermatitis  can cease or is less severe than it was before. [ 8 ]  Topical steroid addiction has also been reported in the male scrotum area. [ 9 ]  Other symptoms include nerve pain, insomnia, excessive sweating, anxiety, severe depression, fatigue, eye problems, and frequent infections.


The duration of acute topical corticosteroid withdrawal is variable; the skin can take months to years to return to its original condition. [ 2 ] [ 10 ]  The duration of steroid use may influence the recovery factor time, with the patients who used steroids for the longest reporting the slowest recovery.


To experience this withdrawal, it generally requires the misuse and/or application of a topical steroid daily for 2 to 4 months, depending on the potency of the topical corticosteroid. In some cases, this has been reported after as little as 2 weeks of use. [ 11 ] [ 1 ]


Historically, it was believed that  cortisol  was only produced by the  adrenal  glands, but research has shown that  keratinocytes  in human skin also produce cortisol. [ 12 ]  Prolonged topical steroid (TS) application changes the glucocorticoid receptor (GR) expression pattern on the surface of lymphocytes; a patient experiencing resistance to a TS has a low ratio of GR-α to GR-β. In addition, the erythema characteristic of ‘red skin syndrome’ is due to a release of stored endothelial nitric oxide (NO) and subsequent vasodilation of dermal vessels. [ 1 ]


Diagnosis is based on a rash occurring within weeks of stopping long-term topical steroids. [ 2 ]  Specific signs include ‘headlight sign’ (redness of the lower part of the face but not the nose or the area around the mouth); ‘red sleeve’ (a rebound eruption stopping abruptly at the lower arms and hands); and ‘elephant wrinkles’ (reduced skin elasticity). [ 3 ]


Differentiating this condition from the skin condition that the steroids were originally used to treat can be difficult. [ 2 ]  Red, burning skin may be misdiagnosed. [ 8 ]


This condition can be avoided by not using steroid creams for periods of time longer than 2 weeks. [ 2 ] [ 3 ]


Treatment involves ceasing all use of topical steroids, either gradually or suddenly. [ 2 ]  Keeping affected areas dry and disinfected will speed healing. [ citation needed ] [ dubious  –  discuss ]  Avoid moisturizer, as any dampness elongates the healing process and encourages bacterial growth. [ citation needed ] [ dubious  –  discuss ]  Antihistamines may help for itchiness. [ 3 ]  Immunosuppressants and light therapy may also help some people. [ 3 ]  Psychological support is often recommended. [ 2 ] [ 3 ] [ 11 ]  At this time, treatment options that have been documented in literature include  Tacrolimus ,  Pimecrolimus , and  Dupixent . Some physicians have also seen positive outcomes with oral  Doxycycline  and/or topical  Clindamycin . [ 13 ]


The prevalence of the condition is unknown. [ 14 ]  Many cases ranging from mild to severe have been reported in both adults and children. One survey of atopic dermatitis patients treated with topical corticosteroids in Japan estimated that approximately 12% of adult patients may appear to be uncontrolled cases, although they are in fact addicted to a topical corticosteroid (TCS). [ 8 ]


A systematic review ( meta-analysis ) in accordance with  evidence-based medicine  frameworks and current research standards for clinical decision-making was performed in 2016 and was republished with updates in 2020. [ 15 ]


Two feet-one hand syndrome  ( TFOHS ), is a long-term  fungal condition  where  athlete's foot  or  fungal toe nail infections  in both feet is associated with  tinea manuum  in one hand. [ 3 ] [ 7 ]  Often the feet are affected for several years before symptoms of a diffuse scaling rash on the palm of one hand appear, which is when most affected people then seek medical help. [ 7 ]


The most common causative organism is  Trichophyton rubrum . [ 3 ]  The condition is more likely to occur in people who  sweat more . [ 4 ]  Diagnosis is by visualization,  microscopy  and  culture . [ 4 ]  It may appear similar to  dermatitis ,  psoriasis ,  keratoderma ,  hyperkeratosis  and  allergic contact dermatitis . [ 5 ]  Treatment is with long-term systemic  antifungals , typically oral  terbinafine  or  itraconazole . [ 4 ] [ 8 ]


The condition is frequently seen in  skin  clinics. [ 9 ]  Males are affected more frequently than females. [ 3 ]  One study showed that 65% of cases with tinea manuum were part of TFOHS. [ 6 ] [ 10 ]  TFOHS was first described by Curtis in 1964. [ 11 ]


TFOHS is a long-term  fungal condition  where  athlete's foot  or  fungal toe nail infections  in both feet is associated with  tinea manuum  in one hand. [ 3 ] [ 7 ]  It typically presents with a diffuse scaling rash on the palm of one hand, which is preceded, sometimes by several years, by fungal infection in both feet. [ 3 ]  Palmar creases appear prominent. [ 1 ]  There is typically a sharp demarcation at the wrist. [ 12 ]  Signs in a hand therefore require an examination of feet. [ 13 ]


TFOHS may follow scratching feet infected by  fungi  or occur after a pedicure. [ 3 ]  The most common causative organism is  Trichophyton rubrum . [ 3 ] [ 2 ]  Typically, the hand that is used to scratch the infected feet or toes is the one that contracts tinea manuum. [ 14 ]  Why the other hand is spared is not clear. [ 15 ] [ 16 ]  In a case-control study that also looked at scratching habits, despite concluding that it was likely that tinea manuum develops in the hand that scratches the feet, some cases of TFOHS occurred in the hand that did not scratch the feet. [ 9 ]


Risk factors are the same as for athlete's foot and include excessive sweating and  weakened immune system . [ 4 ] [ 6 ]  Reinfection from contaminated socks may be possible. [ 4 ]


Diagnosis of TFOHS is by visualisation,  microscopy  and culture from skin scrapings of the edge of the rash. [ 2 ] [ 11 ]  The condition may appear similar to  dermatitis ,  psoriasis ,  keratoderma ,  hyperkeratosis  and  allergic contact dermatitis . [ 5 ]  It is sometimes misdiagnosed as  hand eczema . [ 17 ]


Treatment is with long-term systemic  antifungals , typically oral  terbinafine  or  itraconazole . [ 4 ] [ 8 ]  Other options include  fluconazole  and  griseofulvin . [ 4 ]  Prevention is focused on  hygiene  measures such as keeping feet dry and applying antiseptic powder. [ 4 ]  Using intermittent antifungal treatment in susceptible people, and avoiding scratching the feet or picking at  fungal toenail infections  are further preventative measures. [ 6 ]  Avoiding washing socks in cold water may help, as well as dusting feet with  Tolnaftate  powder. [ 4 ]  Dusting socks with talc, cornstarch or rice powder may help keep feet dry. [ 4 ]