More common than a complete absence of pigment cells is localized or incomplete  hypopigmentation , resulting in irregular patches of white on an animal that otherwise has normal coloring and patterning. This partial leucism is known as a "pied" or " piebald " effect; and the ratio of white to normal-colured skin can vary considerably not only between generations, but between different offspring from the same parents, and even between members of the same litter. This is notable in  horses ,  cows ,  cats ,  dogs , the urban  crow [ 7 ]  and the  ball python [ 8 ]  but is also found in many other species.


Due to the lack of melanin production in both the  retinal  pigmented epithelium (RPE) and  iris , those affected by  albinism  sometimes have pink pupil due to the underlying blood vessels showing through. However, this is not always the case and many albino animals do not have pink pupils. [ 9 ]  The common belief that all albinos have pink pupils results in many albinos being incorrectly labeled as 'leucistic'. The neural crest disorders that cause leucism do not result in pink pupils and therefore most leucistic animals have normally colored eyes. This is because the melanocytes of the RPE do not derive from the  neural crest . Instead, an out-pouching of the  neural tube  generates the  optic cup  that, in turn, forms the  retina . As these cells are from an independent developmental origin, they are typically unaffected by the genetic cause of leucism.


Genes  that, when  mutated , can cause leucism include  c-kit , [ 11 ]   mitf [ 12 ]  and  EDNRB . [ 13 ]


The terms  leucistic  and  leucism  are derived from the stem  leuc-  +  -ism , from Latin  leuco-  in turn derived from  Greek   leukos  meaning  white .


A  lichenoid eruption  is a  skin disease  characterized by damage and  infiltration  between the  epidermis  and  dermis . [ 1 ]


Examples include  lichen planus ,  lichen sclerosus  and  lichen nitidus . It can also be associated with abrasion or drug use. [ 2 ]  It has been observed in conjunction with the use of  proton pump inhibitors , and might be a sign and/or symptom of  lupus  such as  subacute cutaneous lupus erythematous , according to the  case reports  and reviews. [ 3 ] [ 4 ] [ 5 ] [ 6 ]


The term "lichenoid" derives from a resemblance to a  lichen .


A  maculopapular rash  is a type of  rash  characterized by a flat, red area on the skin that is covered with small confluent bumps. It may only appear red in lighter-skinned people. The term "maculopapular" is a compound:  macules  are small, flat discolored spots on the surface of the skin; and  papules  are small, raised bumps. It is also described as  erythematous , or red.


This type of rash is common in several diseases and medical conditions, including  scarlet fever ,  measles ,  Ebola virus disease ,  rubella ,  HIV , secondary  syphilis  (Congenital syphilis, which is asymptomatic, the newborn may present this type of rash),  erythrovirus  ( parvovirus B19 ),  chikungunya  (alphavirus),  zika ,  smallpox  (which has been eradicated),  varicella  (when vaccinated persons exhibit symptoms from the modified form),  heat rash , and sometimes in  Dengue fever . It is also a common manifestation of a skin reaction to the antibiotic  amoxicillin  or  chemotherapy  drugs. [ 1 ]   Cutaneous infiltration of  leukemic  cells may also have this appearance. Maculopapular rash is seen in  graft-versus-host disease  (GVHD) developed after a hematopoietic stem cell transplant (bone marrow transplant), which can be seen within one week or several weeks after the transplant. In the case of GVHD, the maculopapular lesions may progress to a condition similar to  toxic epidermal necrolysis . [ 2 ]  In addition, this is the type of rash that some patients presenting with  Ebola virus  hemorrhagic (EBO-Z) fever will reveal but can be hard to see on dark skin people. [ 3 ]  It is also seen in patients with  Marburg hemorrhagic fever , a  filovirus  not unlike Ebola.


This type of rash can be as a result of large doses of  niacin  or no-flush niacin (2000 – 2500 mg), [ citation needed ]  used for the management of low HDL cholesterol. [ 4 ]


This type of rash can also be a symptom of  Sea bather's eruption . This stinging, pruritic, maculopapular rash affects swimmers in some Atlantic locales (e.g., Florida, Caribbean, Long Island). It is caused by hypersensitivity to stings from the larvae of the sea anemone (e.g.,  Edwardsiella lineate ) or the thimble jellyfish ( Linuche unguiculata ). The rash appears where the bathing suit contacts the skin. [ 5 ]


This type of rash can also be a symptom of acute arsenic intoxication, appearing 2 weeks later. [ 6 ]


A  malar rash  (from  Latin    mala  'jaw, cheek-bone'), also called  butterfly rash , [ 1 ]  is a  medical sign  consisting of a characteristic form of facial  rash . It is often seen in  lupus erythematosus . More rarely, it is also seen in other diseases, such as  pellagra ,  dermatomyositis , and  Bloom syndrome .


There are many conditions which can cause rashes with a similar appearance to a malar rash. A malar rash is present in approximately 46–65% of people with lupus.


A malar rash of lupus is red or purplish and mildly scaly. It has the characteristic shape of a butterfly, and involves the bridge of the nose. Notably, the rash spares the  nasolabial folds  of the face, which contributes to its characteristic appearance. It is usually macular with sharp edges, and not itchy. The rash can be transient or progressive with involvement of other parts of the facial skin. [ citation needed ]


While some literature has described the slapped-cheek rash of  fifth disease  as a malar rash, it differs slightly in that the nose is typically spared. [ 2 ]


There are many conditions which can cause rashes with a similar appearance to a malar rash. [ 1 ]  These include:


Lupus causes up to 96% of all cases of malar rash. [ 3 ]  Where lupus is suspected, further  medical tests  and a detailed history and examination are necessary to  differentiate  it from other conditions. [ citation needed ]  These tests may include a test for the presence of  anti-nuclear antibody  in the blood as a  screening  test, which is not specific for lupus erythematosus. [ citation needed ]


A malar rash is present in approximately 46–65% of people with lupus, [ 7 ] [ 8 ]  with an average of 57% of lupus patients having it across all populations. [ 3 ]  This percentage varies between different populations. [ 7 ] [ 8 ]


A malar rash is often known more  colloquially  as a butterfly rash due to its distinctive appearance. [ 1 ]


The  Malpighian layer  ( stratum mucosum  or  stratum malpighii ) of the  epidermis  is generally defined as both the  stratum basale  (basal layer) and the thicker  stratum spinosum  (spinous layer/prickle cell layer) immediately above it as a single unit, [ 1 ] [ 2 ]  although it is occasionally defined as the stratum basale specifically, [ 3 ]  or the stratum spinosum specifically. [ 4 ]


It is named after the Italian biologist and physician  Marcello Malpighi .


Basal cell carcinoma  originates from the basal layer of the stratum malpighii.


This layer is where almost all of the  mitotic  activity in the  epidermis  occurs. The activity of these cells is increased by IL-1 ( interleukin-1 ) and  epidermal growth factor . The activity is decreased by  transforming growth factor beta . [ 5 ]


Melanism  is the  congenital  excess of  melanin  in an organism resulting in dark  pigment .


Pseudomelanism, also called abundism, is another variant of pigmentation, identifiable by dark spots or enlarged stripes, which cover a large part of the body of the animal, making it appear melanistic. [ 2 ]


The morbid deposition of black matter, often of a malignant character causing pigmented  tumors , is called  melanosis . [ 3 ]


Melanism related to the process of  adaptation  is called adaptive. Most commonly, dark individuals become  fitter  to survive and reproduce in their environment as they are better camouflaged. This makes some species less conspicuous to predators, while others, such as  leopards , use it as a foraging advantage during night hunting. [ 4 ]  Typically, adaptive melanism is  heritable : A  dominant   allele , which is entirely or nearly entirely expressed in the  phenotype , is responsible for the excessive amount of melanin. By contrast, adaptive melanism associated with Batesian mimicry in  Zelandoperla fenestrata   stoneflies  is controlled by a  recessive allele  at the ebony locus. [ 5 ] [ 6 ]


Adaptive melanism has been shown to occur in a variety of animals, including mammals such as  squirrels , many  cats  and  canids , and  coral snakes . Adaptive melanism can lead to the creation of  morphs , a notable example being the  peppered moth , whose evolutionary history in the  United Kingdom  is offered as a classic instructional tool for teaching the principles of  natural selection . [ 7 ]  A more replicated example of human-induced shifts in  melanism  has arisen from repeated selection against melanic  Zelandoperla fenestrata  stonefly phenotypes following widespread  deforestation in New Zealand . [ 5 ] [ 6 ]


Industrial melanism is an  evolutionary  effect in insects such as the peppered moth,  Biston betularia  in areas subject to  industrial pollution . Darker pigmented individuals are favored by  natural selection , apparently because they are better  camouflaged  against polluted backgrounds. When pollution was later reduced, lighter forms regained the advantage and melanism became less frequent. [ 8 ] [ 9 ] [ 10 ] [ 11 ] [ 12 ] [ 13 ]  Other explanations have been proposed, such as that the melanin pigment enhances function of immune defences, [ 14 ]  or a thermal advantage from the darker coloration. [ 15 ] [ 16 ] [ 17 ]


Melanistic coat coloration occurs as a common  polymorphism  in 11 of 37  felid  species and reaches high population frequency in some cases but never achieves complete  fixation . The  black panther , a melanistic  leopard , is common in the  equatorial rainforest  of  Malaya  and the  tropical rainforest  on the slopes of some African mountains, such as  Mount Kenya . The  serval  also has melanistic forms in certain areas of  East Africa . In the  jaguarundi , coloration varies from dark brown and gray to light reddish. Melanic forms of  jaguar  are common in certain parts of  South America . [ 18 ]  In 1938 and 1940, two melanistic  bobcats  were trapped alive in sub-tropical  Florida . [ 19 ]


In 2003, the  dominant  mode of inheritance of melanism in jaguars was confirmed by performing  phenotype -transmission analysis in a 116-individual captive  pedigree . Melanistic animals were found to carry at least one copy of a mutant  MC1R  sequence  allele , bearing a 15- base pair  inframe deletion. Ten unrelated melanistic jaguars were either  homozygous  or  heterozygous  for this allele. A 24-base pair deletion causes the incompletely dominant allele for melanism in the jaguarundi. Sequencing of the  agouti signalling peptide  in the  agouti gene  coding region revealed a 2-base pair deletion in black  domestic cats . These variants were absent in melanistic individuals of  Geoffroy's cat ,  oncilla ,  pampas cat  and  Asian golden cat , suggesting that melanism arose independently at least four times in the cat family. [ 20 ]


Melanism in leopards is inherited as a  Mendelian ,  monogenic   recessive trait  relative to the spotted form. Pairings of black animals have a significantly smaller litter size than other possible pairings. [ 21 ]  Between January 1996 and March 2009,  Indochinese leopards  were photographed at 16 sites in the  Malay Peninsula  in a sampling effort of more than 1000 trap nights. Of 445 photographs of melanistic leopards, 410 were taken south of the  Kra Isthmus , where the non-melanistic morph was never photographed. These data suggest the near fixation of the dark allele in the region. The expected time to fixation of this recessive allele due to  genetic drift  alone ranged from about 1,100 years to about 100,000 years. [ 22 ]
Melanism in leopards has been hypothesized to be causally associated with a selective advantage for ambush. [ 23 ]  Other theories are that genes for melanism in felines may provide resistance to viral infections, or a high-altitude adaptation, since black fur absorbs more light for warmth. [ 24 ]


The chicken breeds  Silkie  and  Ayam Cemani  commonly exhibit this trait.  Ayam Cemani  is an uncommon and relatively modern breed of chicken from Indonesia. They have a dominant gene that causes hyperpigmentation (Fibromelanosis), making the chicken entirely black; including feathers, beak, and internal organs.


Melanism in feral  rock doves  are actually quite common,to some extent, especially if the area is abundant with the species. The amount of pigmentation is varied, from a slight darker pigmentation in the pigeon’s wings, to being almost completely black.


In April 2015, an extremely rare black  flamingo  was spotted on the Mediterranean island of  Cyprus . [ 25 ]


The  alpine salamander ,  Salamandra atra , has one subspecies ( S. atra atra ) that is completely black. [ 26 ]  The pigment comes from a specific cell called a melanophore, which produce the compound melanin. [ 27 ] [ 28 ]


There are four other subspecies of this salamander, [ 29 ]  and they have varying levels of melanin pigmentation. [ 28 ] [ 30 ] [ 31 ]  The subspecies have yellow spots in different concentrations or proportions. The  pigment-producing cells  that contribute to the yellow spots of some sub-species are called xanthophores. [ 30 ]  It appears that the fully-black phenotypes do not ever develop these xanthophores. [ 31 ]  Alpine salamanders produce a toxin from their skin, and both fully melanistic, black salamanders and spotted individuals produce the compound. [ 32 ]


Studies done that traced DNA histories have suggested that the original alpine salamander phenotype was black with some yellow spots, meaning that the fully black color evolved over time and was thus selected for over many generations. [ 31 ]


Melanism, meaning a mutation that results in completely dark skin, does not exist in humans. In humans, the amount of melanin is determined by three dominant alleles (AABBCC), and different ethnicities have varying amounts. [ 33 ]  Melanin is the primary determinant of the degree of skin pigmentation and protects the body from harmful  ultraviolet radiation . The same ultraviolet radiation is essential for the synthesis of  vitamin D  in skin, so lighter colored skin – less melanin – is an adaptation related to the prehistoric movement of humans away from equatorial regions, as there is less exposure to sunlight at higher latitudes. People from parts of Africa,  South Asia ,  Southeast Asia , Australia,  Papua New Guinea ,  Fiji ,  Vanuatu ,  New Caledonia , and the  Solomon Islands  may have very dark skin, but this is not melanism.


This rare  genetic disorder  is characterized by the development of  macules  with  hyperpigmentation  on the lips and  oral mucosa  ( melanosis ), as well as benign polyps in the gastrointestinal tract. [ 34 ]


The term  melanism  has been used on  Usenet ,  internet forums  and  blogs  to mean an  African-American   social movement  holding that dark-skinned humans are the original people from which those of other  skin color  originate. The term  melanism  has been used in this context as early as the mid-1990s [ 35 ]  and was promoted by some  Afrocentrists , such as  Frances Cress Welsing .


Melanosis  is a form of  hyperpigmentation  associated with increased  melanin . [ 1 ]


It can also refer to:


The term  morbilliform  refers to a  rash  that looks like  measles . [ 1 ] [ 2 ]  The rash consists of  macular   lesions  that are red and usually 2–10 mm in diameter but may be confluent in places. [ 3 ]  A morbilliform rash is a rose-red flat ( macular ) or slightly elevated ( maculopapular ) eruption, showing circular or elliptical lesions varying in diameter from 1 to 3 mm, with healthy-looking skin intervening. [ citation needed ]


Patients with measles will have the rash but there are other syndromes and infections that will display the same symptom such as patients with  Kawasaki disease , [ 4 ]   meningococcal   petechiae  or  Waterhouse-Friderichsen syndrome , [ 4 ]   Dengue ,  Roseola , congenital syphilis, [ 5 ]   rubella , [ 4 ]   Echovirus 9 , [ 4 ]  drug hypersensitivity reactions (in particular with certain classes of  antiretroviral drugs , such as  abacavir  and  nevirapine , and also the antiepileptic drug  phenytoin ), or other conditions may also have a morbilliform rash. It has also been mentioned as a possible manifestation of onset or recovery from  COVID-19 . [ 6 ]


One cause of morbilliform rash is an allergic reaction to transfused blood/blood components. In such a case, the skin lesions would develop within a few hours (Approx. 4hours) of transfusion along with pruritus. The condition may even present with other symptoms, such as conjunctival oedema, oedema in the lips and tongue, and even localised angioedema. On rare occasions, the condition may even escalate to anaphylactic shock where pulmonary restrictions are seen. The associated cause for this is a reaction against an allergen that is seldom identified during testing. Transfusing products with anti-IgA antibodies to IgA-deficient patients has also been a suspected cause for such reactions. Management usually relates to the stoppage of transfusion for around 30minutes, until given antihistamines take effect. Transfusion may even be continued after, if no further progression is seen.


Nevi and melanomas  are a group of neoplasia.


Although a  nevus  and a  melanoma  are often treated as independent entities, there is evidence that a nevus can be a precursor for a melanoma. [ 1 ]


Common mutations have been identified in nevi and melanomas. [ 2 ] [ 3 ] [ 4 ]


Nevus  ( pl. :  nevi ) is a nonspecific medical term for a visible, circumscribed,  chronic   lesion  of the  skin  or  mucosa . [ 1 ]  The term originates from  nævus , which is Latin for " birthmark "; however, a nevus can be either congenital (present at birth) or acquired. Common terms, including  mole ,  birthmark , and  beauty mark , are used to describe nevi, but these terms do not distinguish specific types of nevi from one another.


The term  nevus  is applied to a number of conditions caused by  neoplasias  and  hyperplasias  of  melanocytes , [ 2 ]  as well as a number of pigmentation disorders, both hypermelanotic (containing increased  melanin , the pigment responsible for skin color) and hypomelanotic (containing decreased melanin). [ 3 ]  Suspicious skin moles which are multi-colored or pink may be a finding in  skin cancer . [ 4 ]


Additional types of nevi do not involve disorders of pigmentation or melanocytes. These additional nevi represent hamartomatous proliferations of the epithelium, [ 8 ]  connective tissue, [ 9 ]  and vascular malformations. [ 10 ]


These nevi represent excess growth of specific cells types found in the skin, including those that make up oil and sweat glands. [ 8 ]


Connective tissue nevi  represent abnormalities of  collagen  in the dermis, the deep layer of the skin. [ 9 ]


These nevi represent excess growth of blood vessels, including capillaries. [ 11 ]


An  intramucosal nevus  is a nevus within the  mucosa  as found in for example the mouth and genital areas. In the mouth, they are found most frequently on the hard palate. They are typically light brown and dome-shaped. [ 12 ]  Intramucosal nevi account for 64% of all reported case of oral nevi. [ 13 ]


Nevi are typically diagnosed clinically with the naked eye or using  dermatoscopy . More advanced imaging tests are available for distinguishing melanocytic nevi from melanoma, including computerized dermoscopy and image analysis. [ 14 ]  The management of nevi depends on the type of nevus and the degree of diagnostic uncertainty. Some nevi are known to be benign, and may simply be monitored over time. Others may warrant more thorough examination and  biopsy  for histopathological examination (looking at a sample of skin under a microscope to detect unique cellular features). For example, a clinician may want to determine whether a pigmented nevus is a type of melanocytic nevus, dysplastic nevus, or melanoma as some of these skin lesions pose a risk for malignancy. The ABCDE criteria (asymmetry, border irregularity, color variegation, diameter > 6 mm, and evolution) are often used to distinguish nevi from melanomas in adults, while modified criteria (amelanosis, bleeding or bumps, uniform color, small diameter or de novo, and evolution) can be used when evaluating suspicious lesions in children. [ 15 ]   In addition to histopathological examination, some lesions may also warrant additional tests to aid in diagnosis, including special stains,  immunohistochemistry , and electron microscopy. [ 16 ]  Typically, the nevi that exist since childhood are harmless.


Hypermelanotic nevi must be differentiated from other types of pigmented skin lesions, including: [ 6 ] [ 7 ]


The management of a nevus depends on the specific diagnosis, however, the options for treatment generally include the following modalities:


The decision to observe or treat a nevus may depend on a number of factors, including cosmetic concerns, irritative symptoms (e.g., pruritus), ulceration, infection, and concern for potential malignancy. [ 2 ]


The term nevus is included in the names of multiple dermatologic syndromes:


Orthokeratosis  is  hyperkeratosis  without  parakeratosis . No nucleus is seen in the cells. There is also formation of an anuclear keratin layer, [ 1 ]  as in the normal epidermis.


Pagetoid  is a term used in dermatology to refer to "upward spreading" of abnormal cells in the epidermis (ie from bottom to top). It is uncommon and a possible indication of a precancerous or cancerous condition. Cells display pagetoid growth when they invade the upper epidermis from below.  Squamous cell carcinoma ,  melanoma   in situ , Pagetoid  Bowen's disease , ocular sebaceous carcinoma, and other  carcinomas  can all display pagetoid growth.


The term  pagetoid  (i.e., 'Paget-like') is derived from the  extramammary Paget's disease , wherein the large tumour cells are arranged singly or in small clusters within the epidermis and its appendages. These cells are distinguished by a clear halo from the surrounding epithelial cells and a finely granular cytoplasm. [ 1 ]  This proliferation of cells in the epidermis is responsible for the "buckshot scatter" pattern. [ 2 ]  This is a typical feature of superficial spreading type of  melanoma .


Pallor  is a pale color of the  skin  that can be caused by illness, emotional shock or stress, stimulant use, or  anemia , and is the result of a reduced amount of  oxyhaemoglobin  and may also be visible as pallor of the  conjunctivae of the eyes  on physical examination.


Pallor is more evident on the  face  and  palms . It can develop suddenly or gradually, depending on the cause. It is not usually clinically significant unless it is accompanied by a general pallor (pale  lips ,  tongue , palms,  mouth  and other regions with  mucous membranes ). It is distinguished from similar presentations such as  hypopigmentation  (lack or loss of skin  pigment ) or simply a fair complexion.


Papillomatosis  is skin surface elevation caused by  hyperplasia  and enlargement of  contiguous   dermal papillae . [ 1 ]  These papillary projections of the epidermis form an undulating surface under microscopic examination.


A  papule  is a small, well-defined bump in the  skin . [ 2 ]  It may have a rounded, pointed or flat top, and may have a  dip . [ 2 ]  It can appear with a  stalk , be thread-like or look  warty . [ 3 ]  It can be soft or firm and its surface may be rough or smooth. [ 2 ]  Some have  crusts  or  scales . [ 2 ]  A papule can be flesh colored, yellow, white, brown, red, blue or purplish. [ 4 ]  There may be just one or many, and they may occur irregularly in different parts of the body or appear in clusters. [ 2 ]  It does not contain fluid but may progress to a  pustule  or  vesicle . [ 2 ]  A papule is smaller than a  nodule ; it can be as tiny as a pinhead and is typically less than 1 cm in width, according to some sources, [ 2 ] [ 3 ]  and 0.5 cm according to others. [ 4 ]  When merged together, it appears as a plaque. [ 4 ]


A papule's colour might indicate its cause, such as white in  milia , red in  eczema ,  yellowish  in  xanthoma  and black in  melanoma . [ 2 ]  They may open when scratched and become infected and crusty. [ 5 ]


A papule is a small, well-defined bump in the  skin . [ 2 ]  It is smaller than a  nodule ; it can be as tiny as a pinhead and is typically less than 1 cm in width, according to some sources, [ 2 ] [ 3 ]  and 0.5 cm according to others. [ 4 ]


A papule may have a rounded, pointed or flat top, and may have a dip. [ 2 ]   It can be polygonal but is never rectangular or square. [ 6 ]  It can appear with a  stalk , be thread-like or look  warty . [ 3 ]  Ulceration, oozing, bleeding or thin blood vessels may be present in a papule. [ 6 ]  It can be soft or firm and its surface may be rough or smooth. [ 2 ]  Some have  crusts  or  scales . [ 2 ]  A papule can be flesh colored, yellow, white, brown, black, blue or purplish, or varying shades of red. [ 4 ] [ 6 ]  The intensity of redness might indicate how long the papule has been present. [ 6 ]  There may be just one or many, and they may occur irregularly in different parts of the body or appear in clusters. [ 2 ]  It may progress to a pustule or vesicle. [ 2 ]


Angiofibromas  are papules, types of which include the usually solitary  fibrous papule of the nose  and  periungual angiofibroma , and multiple in  pearly penile papules , and the  facial angiofibromas  as may be seen in  tuberous sclerosis . [ 7 ]


Papules with scale on the palms and soles may occur in  secondary syphilis ,  psoriasis ,  eczema ,  tinea manuum ,  mycosis fungoides . [ 6 ]  In  lichen planus  papules may be itchy, flat-topped, polygonal, purplish with white streaks, and can be solitary, or occur in clusters or in a line. [ 6 ]


A  papulopustular  condition is a condition composed of both  papule  and  pustules . [ 1 ]


Examples of papulopustular conditions include:


A  papulosquamous disorder  is a condition which presents with both  papules  and  scales , [ 1 ]  or both scaly papules and  plaques . [ 2 ]


Examples include  psoriasis ,  lichen planus , [ 3 ]  and  pityriasis rosea . [ 4 ]


Parakeratosis  is a mode of  keratinization  characterized by the retention of nuclei in the  stratum corneum . [ 1 ]  In  mucous membranes , parakeratosis is normal. [ 2 ]   In the skin, this process leads to the abnormal replacement of  annular   squames  with  nucleated  cells. Parakeratosis is associated with the thinning or loss of the  granular layer  and is usually seen in diseases of increased cell turnover, whether  inflammatory  or  neoplastic . Parakeratosis is seen in the plaques of  psoriasis  and in  dandruff .


Granular parakeratosis (originally termed axillary granular parakeratosis) is an  idiopathic , benign, nondisabling cutaneous disease that manifests with  intertriginous   erythematous , brown or red, scaly or keratotic  papules  and  plaques . It presents in all age groups and has no established clinical associations. [ 3 ]


Paraneoplastic keratoderma  is a cutaneous condition characterized by a hornlike skin texture associated with an internal malignancy. [ 1 ]


Pathergy  is a skin condition in which a minor trauma such as a bump or bruise leads to the development of skin lesions or ulcers that may be resistant to healing.  Pathergy can also lead to ulcerations at the site of surgical incisions. Pathergy is seen with both  Behçet's disease  and  pyoderma gangrenosum . [ 1 ]   A highly similar phenomenon known as the  Koebner phenomenon  occurs in  autoimmune diseases  such as  psoriasis  and  systemic lupus erythematosus , among others.


Doctors looking toward a diagnosis of Behçet's disease may attempt to induce a pathergy reaction with a test known as a "skin prick test". [ 2 ]  The inflammation and ulceration that occurs as a result of pathergy in pyoderma gangrenosum often responds to systemic steroid therapy.


The pathergy reaction is a unique feature of Behçet's disease and, according to the International Study Group for Behcet's Disease, is among the major criteria required for the diagnosis. Different positive pathergy reaction rates in BD have been reported worldwide. When BD-positive groups are studied for pathergy reaction, the pathergy-positive and pathergy-negative BD groups showed a similar male: female ratio, age at disease onset, and mean disease duration. They also exhibited similar  HLA-B51  levels and a similar frequency of oral ulcerations in close family members. The mucocutaneous manifestations, systemic disease expression, and severity score were similar in patients with and without the pathergy reaction. The presence of a positive pathergy reaction is not associated with an increased risk for specific mucocutaneous or systemic manifestations of the disease, and probably does not predict a more severe disease course. [ 3 ]


It is also important to note that, while a positive pathergy reaction helps to confirm a specific Behçet's disease diagnosis, a negative reaction does not invalidate a BD diagnosis, because the disease process has to be active at the time of the skin prick test to produce a pathergy reaction. Differences in positive/negative pathergy and severity of the reaction depend on disease activity, ethnicity, type of needle used for the prick test, among other factors. [ 2 ]


Pathergy test is done both orally and cutaneous.


Orally, the lower lip is the site of testing. Appearance of any ulcer or papule indicates a positive pathergy reaction.


Cutaneous sites are the flexor forearm.


Physical urticaria  is a distinct subgroup of  urticaria  (hives) that are induced by an exogenous physical stimulus rather than occurring spontaneously. [ 1 ]  There are seven subcategories that are recognized as independent diseases. [ 2 ] [ 3 ]  Physical urticaria is known to be painful, itchy and physically unappealing; it can recur for months to years. [ 4 ]


Urticaria are characterized by dermal  edema  (wheal, swollen) and  erythema  (flare, red), [ 2 ]  also known as hives. [ 5 ]  Hive lesions typically last less than 24 hours and are usually  itchy  (pruritic). [ 2 ]  Hives can appear anywhere on the body and they may change shape, move around, disappear and reappear over short periods of time. [ 5 ]


Acute urticaria (short-term): can develop suddenly and will last less than six weeks. [ 6 ]  About one in six people will have acute hives at one point in their life. [ 6 ]


Chronic urticaria (long-term): can develop suddenly and will persist more than six weeks. [ 6 ]  This type of urticaria is uncommon [ 6 ]  and occurs in only 0.1% of the population. [ 7 ]  20% of people with chronic urticaria report still having problems 10 years after its onset. [ 7 ]


The cause of physical urticaria is unknown but it has been suggested to be an  autoimmune  disease, suggesting that antibodies, which are produced by the immune system to protect humans from foreign microbes, are binding to body tissue and damaging it. [ 8 ]


In some cases physical urticaria can be a symptom of an underlying health issue such as: [ 9 ] [ 10 ]


There are seven sub-categories of physical urticaria:


Antihistamine  agents are the typically prescribed drug for the treatment of physical urticaria. [ 2 ]  They block the effect of histamine, a compound produced by the body which forms a part of the local immune response consequently causing inflammation. [ 6 ]  Some research has suggested that the use of antihistamines and  antagonists  in synergy are better for the treatment of physical urticarias. [ 11 ] [ 12 ] [ better source needed ]


The cascade of events that link the autoantibody-antigen reaction with the production and release of histamine is not well characterized. Therefore, the focus of treatment for physical urticaria has been on characterizing the effectiveness of antihistamines rather than analysis of receptor binding or the pathomechanisms. [ 10 ]


A  pimple  or  zit  is a kind of  comedo  that results from excess  sebum  and dead skin cells getting trapped in the pores of the skin. In its aggravated state, it may evolve into a  pustule  or  papule . [ 1 ]  Pimples can be treated by  acne  medications,  antibiotics , and  anti-inflammatories  prescribed by a physician, or various  over the counter  remedies purchased at a pharmacy.


Sebaceous glands  inside the pore of the skin produce  sebum . When the outer layers of skin shed (a natural and continuous process, normally), dead skin and oily sebum left behind may bond together and form a blockage of the  sebaceous gland  at the base of the skin. This is most common when the skin becomes thicker at  puberty . [ 2 ]  The sebaceous gland continues to produce sebum, which builds up behind the blockage, allowing  bacteria  to grow in the area, including the species  Staphylococcus aureus  and  Cutibacterium acnes , which causes inflammation and infection. Other causes of pimples include family history,  stress , fluctuations in  hormone  levels, hair and skincare products, medication  side effects , and un-diagnosed or underlying medical conditions. [ 3 ]  Pimples can be part of the presentation of  rosacea . [ 4 ]


The American Academy of Dermatology recommends that adults with acne use products labeled as "non-comedogenic", "non-acnegenic", "oil-free" or "won’t clog pores", as they are "least likely" to cause skin irritation or acne. [ 3 ]


Common  over-the-counter medications  for pimples are  benzoyl peroxide ,  salicylic acid ,  adapalene , and antibacterial agents such as  triclosan . These topical medications, which can be found in many creams and gels used to treat acne (acne vulgaris), induce skin to slough off more easily, helping to remove bacteria faster. Before application, the face should be washed with warm water or a topical cleanser and then dried.


A regimen of keeping the affected skin area clean, plus the regular application of these topical medications is usually enough to keep acne under control, if not at bay altogether. The most common product is a topical treatment of benzoyl peroxide, which has minimal risk apart from minor skin irritation that may present similar as a mild allergy. [ 6 ]  Recently,  nicotinamide  (vitamin B 3 ), applied topically, has been shown to be more effective in treatment of pimples than  antibiotics  such as  clindamycin . [ 7 ]  Nicotinamide is not an antibiotic and has no  side effects  typically associated with antibiotics. It has the added advantage of reducing skin  hyperpigmentation  which results in pimple scars. [ 8 ]


Severe acne usually indicates the necessity of prescription medication to treat the pimples. Prescription medications used to treat acne and pimples include  isotretinoin , which is a  retinoid , anti-seborrheic medications, anti-androgen medications, hormonal treatments,  alpha hydroxy acid ,  azelaic acid , and  keratolytic  soaps. [ 9 ]


Historically,  antibiotics  such as  tetracyclines  and  erythromycin  were prescribed. While they were more effective than topical applications of benzoyl peroxide, the bacteria eventually grew resistant to the antibiotics and the treatments became less and less effective. Also, antibiotics had more side effects than topical applications, such as stomach cramps and severe discoloration of teeth. Common antibiotics prescribed as of 2001 by dermatologists included  doxycycline  and minocycline. [ 10 ]


Isotretinoin  is used primarily for severe cystic acne and acne that has not responded to other treatments. [ 11 ] [ 12 ] [ 13 ] [ 14 ]  Many dermatologists also support its use for treatment of lesser degrees of acne that prove resistant to other treatments, or that produce physical or psychological scarring. [ 15 ]  It is  teratogenic , and requires strict prevention of pregnancy during its use.


Expression, the manual bursting of pimples which have evolved into  whiteheads  with one's fingers (colloquially, "popping"), can allow bacteria to be introduced into the open wound this creates. This can result in infection and permanent scarring. Thus expression is generally recommended against by  dermatologists  and  estheticians  in favour of allowing pimples to run through their natural lifespans. [ 16 ] [ 17 ] [ 18 ] [ 19 ] [ 20 ]  Some dermatologists offer incision and drainage services to sterilely drain the pimple. [ 21 ]


Pityriasis  commonly refers to flaking (or scaling) [ 1 ]  of the  skin . The word comes from the Greek πίτυρον ' bran '.


Poliosis circumscripta , commonly referred to as a "white  forelock ", is a condition characterized by localized patches of white hair due to a reduction or absence of  melanin  in hair follicles. Although traditionally associated with the scalp, poliosis can affect any hairy area on the body, including eyebrows, eyelashes, and beards. Microscopically, poliosis is marked by the lack of melanin or  melanocytes  in the  hair bulbs , though  epidermal  melanocytes typically remain unaffected unless associated with conditions like  vitiligo . [ 1 ]


Poliosis can be congenital and often occurs in the context of various genetic syndromes. These disorders are typically linked to other systemic manifestations.


In addition to genetic factors, poliosis can develop due to various inflammatory, autoimmune, or  neoplastic  conditions, or as a side effect of medication.


Several genetic and acquired disorders can mimic poliosis, and they should be considered during diagnosis:


Poliosis occurs in several genetic syndromes such as  piebaldism ,  Waardenburg syndrome ,  neurofibromatosis type I , and  tuberous sclerosis . [ 16 ]  It can also occur in conditions such as  vitiligo ,  Vogt–Koyanagi–Harada disease ,  alopecia areata , and  sarcoidosis , and in association with  neoplasms  and some medications. [ 17 ]


Psoriasis Area and Severity Index  ( PASI ) is the most widely used tool for the measurement of severity of  psoriasis . PASI combines the assessment of the severity of  lesions  and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease). [ 1 ]


The body is divided into four sections ( head  (H) (10% of a person's  skin );  arms  (A) (20%);  trunk  (T) (30%);  legs  (L) (40%)). Each of these areas is scored by itself, and then the four scores are combined into the final PASI. For each section, the percent of area of skin involved, is estimated and then transformed into a grade from 0 to 6:


Within each area, the severity is estimated by three clinical signs:  erythema  (redness),  induration  (thickness) and  desquamation  (scaling). Severity parameters are measured on a scale of 0 to 4, from none to maximum.


The sum of all three severity parameters is then calculated for each section of skin, multiplied by the area score for that area and multiplied by weight of respective section (0.1 for head, 0.2 for arms, 0.3 for body and 0.4 for legs).


PASI is widely used in clinical trials of therapies to treat psoriasis. Although absolute PASI score is often used to define entry into a trial, it is response to treatment that is important to measure efficacy and outcomes. This is usually presented as a percentage response rate; e.g., PASI 50, PASI 75, PASI 90, PASI 100.


PASI 75, for example, represents the percentage (or number) of patients who have achieved a 75% or more reduction in their PASI score from baseline. PASI 100 indicates patients who have achieved a complete resolution of all disease. By definition a patient who has achieved PASI 75 has also achieved PASI 50. There is a gradual tendency, as therapies become more effective to report higher efficacy rates in clinical trials - but aiming high may not be without risk of over-treating some patients. [ 2 ]


Psoriatic  area  assessment and  severity  assessments were found to be non-reproducible. Several automated procedure for more reproducible measurement of psoriatic area were developed, but were not suitable for large-scale  trials .  A method where the advantage of accurate computerized measurement of the area on the digital photograph was combined with physician's proficiency in determination of the edge of psoriatic lesion was published. [ 3 ]  The patients were examined and photographed before and after the therapy with calcipotriol ointment or placebo. The psoriatic area was manually outlined on the patient's photographs by physician and the area was automatically measured by a computer. For comparison, the physicians also made standard psoriatic area assessment.  Computer-aided measurement of psoriatic lesion area was found to improve the power of the clinical trial, compared to the standard approach.  The physician's estimations of the psoriatic lesion area tend to overestimate. The adapted PASI index, where the psoriatic area was not converted into an area grade, but was maintained as a continuous variable, also improved the power of the clinical trial.  The modified PASI which involves computer-aided area measurement as a continuous variable is named  Computer aided  psoriasis  continuous  area and severity score cPcASI.


PASI can be too unwieldy to use outside of trials, which has led to attempts to simplify the index (SPASI) for clinical use. [ 4 ]


While higher PASI scores indicate more severe psoriasis, it is difficult for patients or doctors to describe the clinical severity for any specific PASI number.  Attempts have been made to address this problem by providing descriptions of psoriasis severity in evaluation systems, including the Psoriasis Global Assessment (PGA) and the Lattice-System Physician's Global Assessment (LS-PGA); a study compared and validated PASI, PGA, and LS-PGA. [ 5 ]


Purpura  ( / ˈ p ɜːr p jʊər ə / [ 1 ] ) is a condition of  red or purple discolored spots on the  skin  that do not  blanch  on applying pressure. The spots are caused by  bleeding  underneath the skin secondary to platelet disorders, vascular disorders, coagulation disorders, or other causes. [ 2 ]  They measure 3–10 mm, [ 3 ]  whereas  petechiae  measure less than 3 mm, and  ecchymoses  greater than 1 cm. [ 4 ]


Purpura is common with  typhus  and can be present with  meningitis  caused by meningococci or  septicaemia .  In particular, meningococcus ( Neisseria meningitidis ), a  Gram-negative  diplococcus organism, releases endotoxin when it  lyses .  Endotoxin activates the Hageman factor (clotting factor XII), which causes  disseminated intravascular coagulation  (DIC).  The DIC is what appears as a rash on the affected individual.


Purpura are a common and nonspecific medical sign; however, the underlying mechanism commonly involves one of:


Cases of  psychogenic  purpura are also described in the medical literature, [ 6 ]  some claimed to be due to "autoerythrocyte sensitization". Other studies [ 7 ]  suggest the local (cutaneous) activity of  tissue plasminogen activator  can be increased in psychogenic purpura, leading to substantial amounts of localized plasmin activity, rapid degradation of fibrin clots, and resultant bleeding. Petechial rash is also characteristic of a  rickettsial  infection.


The word  purpura  ( / ˈ p ɜːr p ɜːr ə / ) comes from Latin  purpura , " purple ", which came from ancient Greek πορφύρα.  Purpura  is a  mass noun  naming the condition or state, not the name of an individual spot (thus there is no * purpurum , * purpura  or * purpura , * purpurae  count declension).


Pyoderma  means any  skin disease  that is  pyogenic  (has pus). These include superficial bacterial infections such as  impetigo ,  impetigo contagiosa ,  ecthyma ,  folliculitis ,  Bockhart's impetigo ,  furuncle ,  carbuncle ,  tropical ulcer , etc. [ 1 ] [ 2 ]   Autoimmune  conditions include  pyoderma gangrenosum . Pyoderma affects more than 111 million children worldwide, making it one of the three most common skin disorders in children along with  scabies  and  tinea . [ 1 ]


A  rash  is a change of the  skin  that affects its color, appearance, or texture.


A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color,  itch , become warm, bumpy,  chapped , dry, cracked or  blistered , swell, and may be painful.
The causes, and therefore treatments for rashes, vary widely. Diagnosis must take into account such things as the appearance of the rash, other symptoms, what the patient may have been exposed to, occupation, and occurrence in family members. The diagnosis may confirm any number of conditions.
The presence of a rash may aid diagnosis; associated signs and symptoms are diagnostic of certain diseases. For example, the rash in  measles  is an  erythematous ,  morbilliform ,  maculopapular rash  that begins a few days after the fever starts. It classically starts at the head, and spreads downwards.


Common causes of rashes include:


Uncommon causes:


The causes of a rash are numerous, which may make the evaluation of a rash extremely difficult. An accurate evaluation by a provider may only be made in the context of a thorough history, i.e. medications the patient is taking, the patient's occupation, where the patient has been and complete physical examination. [ citation needed ]


Points typically noted in the examination include: [ citation needed ]


A  patch test  may be ordered, for diagnostic purposes. [ 9 ]


Treatment differs according to which rash a patient has been diagnosed with. Common rashes can be easily remedied using steroid topical creams (such as  hydrocortisone ) or non-steroidal treatments. Many of the medications are available over the counter in the United States. [ 10 ]


The problem with steroid topical creams i.e. hydrocortisone; is their inability to penetrate the skin through absorption and therefore not be effective in clearing up the affected area, thus rendering the hydrocortisone almost completely ineffective in all except the most mild of cases. [ 11 ]


The  SCORAD  ("SCORing Atopic Dermatitis") index is a clinical tool for assessing the extent of the disease, disease intensity, and subjective symptoms of  atopic dermatitis . [ 1 ]  It gives approximate weights of 60% to intensity and 20% each to extent and subjective symptoms. These are used to calculate a maximum total score of 103, however, the scores for each category can be used individually if clinically appropriate. [ 2 ]


The SCORAD index was developed by the European Task Force on Atopic Dermatitis in 1993. [ 3 ]  The index was the most widely used disease-severity scale for atopic dermatitis between its development and 2010. [ 4 ]


To calculate the SCORAD index, the extent of disease is determined using the  rule of nines  to estimate percentage of the affected body surface area. The maximum value for the extent of the disease is 100%.


Disease intensity is then calculated based on six characteristics:  erythema ,  edema , oozing/crusts, excoriations,  lichenification , and dryness. Each characteristic is given a score between 0 and 3, where 0 is absent and 3 is severe. The scores for each characteristic are added together for a total intensity score of up to 18.


Subjective symptoms including sleep loss and  pruritus  are measured using a 10 cm  visual analogue scale  with a total maximum score of 20.


The SCORAD index is then calculated with the following formula:


The  SCORTEN scale  (SCORe of Toxic Epidermal Necrosis) is a severity-of-illness scale with which the severity of certain  bullous  conditions can be systematically determined. It was originally developed for  toxic epidermal necrolysis , [ 1 ]  but can be used with burn victims, sufferers of  Stevens–Johnson syndrome , cutaneous drug reactions, or exfoliative wounds. [ citation needed ]  These conditions have in common that they compromise the integrity of the skin and/or mucous membranes.


In the SCORTEN Scale 7 independent risk factors for high mortality are systematically scored, so as to determine the  mortality rate  for that particular patient.


The more risk factors present, the higher the SCORTEN score, and the higher the mortality rate, as shown in the following table.


A  skin fissure  is a  cutaneous condition  in which there is a linear-like cleavage of  skin , sometimes defined as extending into the  dermis . [ 1 ]  It is smaller than a skin  laceration .


A skin area on which there are many skin fissures is called  cracked skin , and is most commonly a result of  skin dryness .  Ichthyosis  is a  genetic disorder  where there is often severe skin cracking.


Spongiosis  is mainly intercellular [ 1 ]   edema  (abnormal accumulation of fluid) in the  epidermis , [ 2 ]  and is characteristic of eczematous  dermatitis , manifested clinically by intraepidermal  vesicles  (fluid-containing spaces), "juicy"  papules , and/or  lichenification . [ 3 ]  It is a severe case of eczema that affects the epidermis, dermis or subcutaneous skin tissues. [ 4 ]  The three types of spongiotic dermatitis are acute, subacute and chronic. [ 4 ]  A dermatologist can diagnose acute spongiotic dermatitis by examining the skin during an office visit, but a biopsy is needed for an accurate diagnosis of the type. [ medical citation needed ]


It can be caused by several internal or external factors, such as food, an insect bite, stress, medication or cosmetics. The treatment varies depending on the type and severity; it is normally treated with topical corticosteroid cream. [ medical citation needed ]


Telangiectasias  (from   tel-  'end'   angi-  ' blood vessel ' and    ectasia  'the expansion of a hollow or tubular organ'), also known as  spider veins , are small  dilated  blood vessels [ 1 ]  that can occur near the surface of the skin or  mucous membranes , measuring between 0.5 and 1 millimeter in diameter. [ 2 ]  These dilated blood vessels can develop anywhere on the body, but are commonly seen on the face around the nose, cheeks and chin. Dilated blood vessels can also develop on the legs, although when they occur on the legs, they often have underlying  venous reflux  or "hidden varicose veins" (see  Venous hypertension  section below). When found on the legs, they are found specifically on the upper thigh, below the  knee joint  and around the ankles.


Many patients with spider veins seek the assistance of physicians who specialize in vein care or peripheral vascular disease. These physicians are called  vascular surgeons  or  phlebologists . More recently,  interventional radiologists  have started treating venous problems.


Some telangiectasias are due to developmental abnormalities that can closely mimic the behaviour of  benign   vascular neoplasms . They may be composed of abnormal aggregations of  arterioles ,  capillaries  or  venules . Because telangiectasias are vascular lesions, they  blanch  when tested with  diascopy .


Telangiectasias, aside from presenting in many other conditions, are one of the features of the acronymically named  CREST syndrome , a form of  systemic scleroderma . The syndrome recognises the significantly co-presenting symptoms of  calcinosis ,  Raynaud's phenomenon ,  esophageal dysmotility ,  sclerodactyly  and telangiectasia.


The causes of telangiectasia can be divided into  congenital  and acquired factors.


Goldman states that "numerous inherited or congenital conditions display cutaneous telangiectasia". [ 2 ]  These include:


In the past, it was believed that leg varicose veins or telangiectasia were caused by high venous pressure or "venous hypertension". However it is now understood that venous reflux disease is usually the cause of these problems. [ 4 ] [ full citation needed ]


Telangiectasia in the legs is often related to the presence of venous reflux within underlying  varicose veins . Flow abnormalities in smaller veins known as  reticular veins  or  feeder veins  under the skin can also cause spider veins to form, thereby making a recurrence of spider veins in the treated area less likely.


Factors that predispose to the development of  varicose  and telangiectatic leg veins include


Acquired telangiectasia, not related to other venous abnormalities, for example on the face and trunk, can be caused by factors such as


Before any treatment of leg telangiectasia is considered, it is essential to have  duplex ultrasonography , the test that has replaced Doppler ultrasound. The reason for this is that there is a clear association between leg telangiectasia and underlying venous reflux. [ 12 ]  Research has shown that 88–89% of women with telangiectasia have refluxing reticular veins close, [ 13 ]  and 15% have incompetent  perforator veins  nearby. [ 14 ]  As such, it is essential to both find and treat underlying venous reflux before considering any treatment at all.


Sclerotherapy  is the "gold standard" and is preferred over laser for eliminating telangiectasiae and smaller varicose leg veins. [ 15 ]  A sclerosant medication is injected into the diseased vein so it hardens and eventually shrinks away. Recent evidence with foam sclerotherapy shows that the foam containing the irritating sclerosant quickly appears in the patient's heart and lungs, and then in some cases travels through a patent foramen ovale to the brain. [ 16 ]  This has led to concerns about the safety of sclerotherapy for telangiectasias.


In some cases  stroke  and  transient ischemic attacks  have occurred after sclerotherapy. [ 17 ]   Varicose veins  and reticular veins are often treated before treating telangiectasia, although treatment of these larger veins in advance of sclerotherapy for telangiectasia may not guarantee better results. [ 18 ] [ 19 ] [ 20 ]  Varicose veins can be treated with foam sclerotherapy,  endovenous laser treatment ,  radiofrequency ablation , or open surgery.  The biggest risk, however, seems to occur with sclerotherapy, especially in terms of  systemic risk  of  DVT ,  pulmonary embolism , and stroke. [ citation needed ]
Other issues which arise with the use of sclerotherapy to treat spider veins are staining, shadowing, telangiectatic matting, and ulceration.  In addition, incompleteness of therapy is common, requiring multiple treatment sessions. [ 21 ]


Telangiectasias on the face are often treated with a laser. Laser therapy uses a light beam that is pulsed onto the veins in order to seal them off, causing them to dissolve. These light-based treatments require adequate heating of the veins.  These treatments can result in the destruction of  sweat glands , and the risk increases with the number of treatments. [ citation needed ]


The  triple response of Lewis  is a cutaneous response that occurs from firm stroking of the  skin . This produces an initial  red  line, followed by a flare around that line, and then finally a  wheal .


The triple response consists of three aspects:


The red spot emerges within 15  seconds . [ 4 ]  Flare can take up to 45 seconds to begin. [ 4 ]  Wheal can take up to 3  minutes  to begin. [ 4 ] [ 5 ]


The triple response is caused by firm stroking of the skin with a pointed object. [ 5 ]   but some time at caused by capillary vasodilation. [ citation needed ]
The triple response of Lewis is particularly sensitive in people with  dermatographia urticaria . [ 4 ] [ 5 ]  Some form of dermatographia is present in around 5% of the population. [ 4 ]


The triple response of Lewis is due to the release of  histamine .  Histamine , or 2-(imidazol-4-yl)ethanamine, is a dibasic  vasoactive   amine  that is located in most body tissues but is highly concentrated in the lungs, skin, and gastrointestinal tract. Histamine is a  small molecule , stored in granules of  mast cells  and  basophils . Mast cells and basophils are the effector cells involved in the immediate hypersensitivity response. Found in tissues throughout the body, they are particularly associated with blood vessels and nerves, and are in proximity to surfaces that border the external environment.


The underlying  pathophysiology  of  frostbite  is a combination of freezing, vascular insufficiency (constriction and occlusion) and damage due to inflammatory mediators. As extremities cool, the ‘hunting response of Lewis’ (alternating vasoconstriction and vasodilation) occurs, ending with vasoconstriction. [ 1 ]


An  ulcer  is a sore on the  skin  or a  mucous membrane , accompanied by the disintegration of tissue. Ulcers can result in complete loss of the  epidermis  and often portions of the  dermis  and even  subcutaneous fat . Ulcers are most common on the skin of the  lower extremities  and in the  gastrointestinal tract . An ulcer that appears on the skin is often visible as an inflamed tissue with an area of reddened skin. A skin ulcer is often visible in the event of exposure to heat or cold, irritation, or a problem with  blood circulation .


They can also be caused due to a lack of mobility, which causes prolonged pressure on the tissues. This stress in the blood circulation is transformed to a skin ulcer, commonly known as  bedsores or decubitus ulcers . [ 1 ]  Ulcers often become  infected , and  pus  forms.


Skin ulcers appear as open craters, often round, with layers of skin that have eroded. The skin around the ulcer may be red, swollen, and tender. Patients may feel pain on the skin around the ulcer, and fluid may ooze from the ulcer. In some cases, ulcers can  bleed  and, rarely, patients experience  fever . Ulcers sometimes seem not to heal; healing, if it does occur, tends to be slow. Ulcers that heal within 12 weeks are usually classified as  acute , and longer-lasting ones as  chronic . [ 2 ]


Ulcers develop in stages. In stage 1 the skin is red with soft underlying  tissue . In the second stage the redness of the skin becomes more pronounced, swelling appears, and there may be some  blisters  and loss of outer skin layers. During the next stage, the skin may become  necrotic  down through the deep layers of skin, and the  fat  beneath the skin may become exposed and visible. In stage 4, deeper necrosis usually occurs, the fat underneath the skin is completely exposed, and the  muscle  may also become exposed. In the last two stages the sore may cause a deeper loss of fat and necrosis of the muscle; in severe cases it can extend down to  bone  level, destruction of the bone may begin, and there may be  sepsis  of  joints .


Chronic ulcers may be  painful . Most patients complain of constant pain at night and during the day. Chronic ulcer symptoms usually include increasing pain, friable granulation tissue, foul odour, and wound breakdown instead of healing. [ 3 ]  Symptoms tend to worsen once the wound has become infected.


Venous skin ulcers  that may appear on the lower leg, above the  calf  or on the lower  ankle  usually cause achy and swollen legs. If these ulcers become infected they may develop an unpleasant odour, increased tenderness and redness. Before the ulcer establishes definitively, there may be a dark red or purple skin over the affected area as well as a thickening, drying, and itchy skin.


Although skin ulcers do not seem of great concern at a first glance, they are worrying conditions especially in people with  diabetes , as they are at risk of developing diabetic  neuropathy .


Ulcers may also appear on the  cheeks ,  soft palate , the  tongue , and on the inside of the lower  lip . These ulcers usually last from 7 to 14 days and can be painful. [ 4 ]


Different types of discharges from ulcer are: [ 5 ]


The wounds from which ulcers arise can be caused by a wide variety of factors, but the main cause is impaired blood circulation. Especially,  chronic wounds  and ulcers are caused by poor circulation, either through cardiovascular issues or external pressure from a  bed  or a  wheelchair . [ 3 ]  A very common and dangerous type of skin ulcer is caused by what are called pressure-sensitive sores, more commonly called bed sores, which are frequent in people who are bedridden or who use wheelchairs for long periods. [ citation needed ]


Other causes producing skin ulcers include  bacterial  and  viral infections ,  fungal infections   [ 6 ]  and  cancers . Blood disorders and chronic wounds can result in skin ulcers as well. [ 7 ]  Venous leg ulcers due to impaired circulation or a blood flow disorder are more common in the  elderly .


Rare causes of skin ulcers include pyoderma gangraenosum, lesions caused by Crohn's disease or ulcerative colitis, granulomatosis with polyangiitis, morbus Behçet and infections that are usually seen in those who are immunocompromised, for example ecthyma gangraenosum. It is important to consider such causes if the skin ulcerations don't show improvement with antibiotic treatments and when other systemic symptoms are present. It is advised not to use surgical procedures on ulcerations caused by Behçet or pyoderma gangraenosum since those diseases usually exhibit  pathergy .


Wagner's grading of ulcer follows: [ 5 ]


Some of the investigations done for ulcer are: [ 5 ] : 19


Skin ulcers may take a very long time to heal. Treatment is typically to avoid the ulcer getting infected, remove any excess discharge, maintain a moist wound environment, control the  edema , and ease pain caused by  nerve  and tissue damage.


Topical antibiotics  are normally used to prevent the ulcer getting infected, and the wound or ulcer is usually kept clear of dead tissue through surgical  debridement .


Commonly, as a part of the treatment, patients are advised to change their lifestyle if possible and to change their  diet . Improving the  circulation  is important in treating skin ulcers, and patients are consequently usually recommended to  exercise , stop  smoking , and lose weight.


In recent years, advances have been made in accelerating healing of  chronic wounds  and ulcers. Chronic wounds produce fewer growth  hormones  than necessary for healing tissue, and healing may be accelerated by replacing or stimulating growth factors while controlling the formation of other substances that work against them. [ 8 ]


Leg ulcers can be prevented by using  compression stockings  to prevent blood pooling and back flow. It is likely that a person who has had a skin ulcer will have it again; use of compression stockings every day for at least five years after the skin ulcer has healed may help to prevent recurrence.


There is limited evidence that  negative-pressure wound therapy  may be effective in reducing the time to healing of leg ulcers. [ 9 ]


Ulerythema  means "scar plus redness," and refers to several different cutaneous conditions, including  atrophoderma vermiculatum  and  keratosis pilaris atrophicans faciei . [ 1 ] : 1511


This  Genodermatoses  article is a  stub . You can help Wikipedia by  expanding it .


Vacuolar interface dermatitis  ( VAC , also known as  liquefaction degeneration ,  vacuolar alteration  or  hydropic degeneration ) is a  dermatitis  with  vacuolization  at the  dermoepidermal junction , with lymphocytic inflammation at the epidermis and dermis. [ 1 ]


An interface dermatitis with  vacuolar  alteration, not otherwise specified, may be caused by viral  exanthems ,  phototoxic dermatitis , acute  radiation dermatitis ,  erythema dyschromicum perstans ,  lupus erythematosus  and  dermatomyositis . [ 2 ]


The  vermilion border  (sometimes spelled  vermillion border ), also called margin or zone, is the normally sharp demarcation between the  lip  and the adjacent normal  skin . It represents the change in the  epidermis  from highly  keratinized  external skin to less keratinized internal skin. It has no  sebaceous glands ,  sweat glands , or  facial hair . [ 1 ] [ 2 ]


It has a prominence on the face, creating a focus for  cosmetics  (it is where  lipstick  is sometimes applied) and is also a location for several skin diseases. Its functional properties, however, remain unknown. [ 3 ]


The lips are composed wholly of soft tissue. The skin of the face is thicker than the skin overlying the lips where blood vessels are closer to the surface. As a consequence, the margin of the lips shows a transition between the thicker and thinner skin, represented by the vermilion border. It therefore has the appearance of a sharp line between the coloured edge of the lip and adjoining skin. [ 4 ]


It has been described as a pale, white rolled border and also as being a red line. [ 1 ] [ 5 ]


This fine line of pale skin accentuates the colour difference between the  vermilion  and normal skin. Along the upper lip, two adjacent elevations of the vermilion border form the  Cupid's bow . [ 6 ]


The vermilion border represents the change in the epidermis from highly  keratinized  external skin to less keratinized internal skin. It has no  sebaceous glands ,  sweat glands , or  facial hair . [ 2 ] [ 1 ]


There are two reasons that the border appears red in some people:


The  vermilion border  is important in  dentistry  and  oral pathology  as a marker to detect  disease , such as in  actinic cheilitis . [ 9 ]


A  vermilionectomy  (sometimes spelled  vermillionectomy ) is the surgical removal of the vermilion border. It is sometimes performed to treat  carcinoma  of the lip. [ 16 ]


Close attention is given when repairing any injury to the vermilion border. Even 1 mm of vermilion misalignment could be noticeable. [ 5 ]


Xanthosis  is a yellowish discoloration of degenerating  tissues , especially seen in malignant  neoplasms . It can be differentiated clinically from  jaundice  as the  sclerae  are colored yellow in jaundice, but are not discolored in xanthosis. [ 1 ]


Xanthosis, or yellows, is a mid 20th century term for  strawberry mild yellow-edge virus , a disease in strawberries, cause by the  strawberry aphid . The disease is prevalent throughout the Americas. [ 2 ]


Xanthosis is a brown pigmentation of  skeletal  and  heart muscles  of cattle. The condition is particularly seen in older animals, and in some wasting diseases. [ 3 ]  Prevalent in  Ayrshire cattle  and their crosses. [ 4 ]


It was the championship word used in the 1995  Scripps National Spelling Bee , and was also featured in the film  Akeelah and the Bee . [ 5 ]


Xeroderma ,  xerosis  or  xerosis cutis , or simply  dry skin , is a  skin condition  characterized by excessively dry  skin . [ 2 ]  The term derives from  Greek     ξηρός  (xeros)  'dry' and    δέρμα  (derma)  'skin'.


In most cases, dry skin can safely be treated with  moisturizers  (also called emollients). Xeroderma occurs most commonly on the  scalp , lower  legs ,  arms , hands,  knuckles , the sides of the  abdomen , and  thighs . Symptoms most associated with xeroderma are such  skin conditions  as scaling (the visible peeling of the outer skin layer),  itching , and  skin fissures  (cracked skin). [ 3 ]


Xeroderma is a very common condition. It happens more often in the winter when the cold air outside and the hot air inside create a low  relative humidity . This causes the skin to lose moisture and it may crack and peel.  Bathing  or  hand washing  too frequently, especially if one is using harsh  soaps , can contribute to xeroderma. Xeroderma can be caused by a deficiency of  vitamin A ,  vitamin D ,  zinc ,  systemic illness , severe  sunburn , or some  medication . [ 4 ]  Xeroderma can be caused by  choline inhibitors .  Detergents  such as  washing powder  and  dishwashing liquid  can cause xeroderma. [ 5 ]


Today, many creams and lotions, commonly based on vegetable oils/butters, petroleum oils/jellies, and  lanolin  are widely available. As a preventive measure, such products may be rubbed onto the affected area as needed (often every other day) to prevent dry skin. The skin is then patted dry to prevent the removal of natural lipids from the skin. Taking a shower or washing hands with special moisturizing soaps or body washes can protect the skin from drying out further.


Repeated application (typically over a few days) of  emollients  or skin lotions/creams to the affected area will likely result in quick alleviation of xeroderma. In particular, the application of highly occlusive barriers to moisture, such as  petrolatum , vegetable oils/butters, and  mineral oil  have been shown to provide excellent results.  Many individuals find specific commercial skin creams and lotions (often comprising oils, butters, and or waxes emulsified in water) quite effective (although individual preferences and results vary among the wide array of commercially available creams). [ 6 ]


Lanolin , a natural mixture of lipids derived from sheep's wool, helps replace natural lipids in human skin and has been used since ancient times (and in modern medicine) as among the most powerful treatments for xeroderma. Some people may, however, have allergies to lanolin, producing the opposite of the desired effect. [ 7 ]  Also, pure lanolin is a thick waxy substance which, for many individuals, proves difficult and inconvenient for general use on dry skin (especially over large areas of the body).  As a result, many formulated lanolin products, having a softer consistency than pure lanolin, are available. [ citation needed ]


Many skin creams include common allergens such as fragrances,  parabens , and lanolin. [ 8 ]


Xerostomia , also known as  dry mouth , is a subjective complaint of dryness in the  mouth , which may be associated with a change in the composition of  saliva , or reduced salivary flow, or  have no identifiable cause . [ 1 ]


This symptom is very common and is often seen as a  side effect  of many types of medication. It is more common in older people (mostly because this group tend to take several medications) and in people who  breathe through their mouths .  Dehydration ,  radiotherapy  involving the  salivary glands ,  chemotherapy  and several diseases can cause reduced salivation (hyposalivation), or a change in saliva consistency and hence a complaint of xerostomia. Sometimes there is no identifiable cause, and there may sometimes be a  psychogenic  reason for the complaint. [ 1 ]


Xerostomia is the subjective sensation of dry mouth, which is often (but not always) associated with hypofunction of the salivary glands. [ 3 ]  The term is derived from the Greek words ξηρός ( xeros ) meaning "dry" and στόμα ( stoma ) meaning "mouth". [ 4 ] [ 5 ]  A drug or substance that increases the rate of salivary flow is termed a  sialogogue .


Hyposalivation  is a clinical diagnosis that is made based on the history and examination, [ 1 ]  but reduced salivary flow rates have been given objective definitions. Salivary gland hypofunction has been defined as any objectively demonstrable reduction in whole and/or individual gland flow rates. [ 6 ]  An unstimulated whole saliva flow rate in a normal person is 0.3–0.4 ml per minute, [ 7 ]  and below 0.1 ml per minute is significantly abnormal. A stimulated saliva flow rate less than 0.5 ml per gland in 5 minutes or less than 1 ml per gland in 10 minutes is decreased. [ 1 ]  The term subjective xerostomia is sometimes used to describe the symptom in the absence of any clinical evidence of dryness. [ 8 ]  Xerostomia may also result from a change in composition of saliva (from serous to mucous). [ 6 ]   Salivary gland dysfunction  is an  umbrella term  for the presence of xerostomia, salivary gland hyposalivation, [ 6 ]  and  hypersalivation . [ citation needed ]


Hyposalivation may give the following signs and symptoms:


However, sometimes the clinical findings do not correlate with the symptoms experienced. [ 9 ]  For example, a person with signs of hyposalivation may not complain of xerostomia. Conversely a person who reports experiencing xerostomia may not show signs of reduced salivary secretions (subjective xerostomia). [ 8 ]  In the latter scenario, there are often other oral symptoms suggestive of  oral dysesthesia  ("burning mouth syndrome"). [ 3 ]  Some symptoms outside the mouth may occur together with xerostomia.


These include:


There may also be other systemic signs and symptoms if there is an underlying cause such as  Sjögren's syndrome , [ 1 ]  for example, joint pain due to associated  rheumatoid arthritis .


The differential of hyposalivation significantly overlaps with that of xerostomia. A reduction in saliva production to about 50% of the normal unstimulated level will usually result in the sensation of dry mouth. [ 8 ]  Altered saliva composition may also be responsible for xerostomia. [ 8 ]


Salivary flow rate is decreased during sleep, which may lead to a transient sensation of dry mouth upon waking. This disappears with eating or drinking or with oral hygiene. When associated with halitosis, this is sometimes termed "morning breath". Dry mouth is also a common sensation during periods of anxiety, probably owing to enhanced  sympathetic  drive. [ 11 ]  During periods of stress, our body responds in a ‘fight or flight’ state that will interfere with the saliva flow in the mouth. [ 12 ]  Dehydration is known to cause hyposalivation, [ 1 ]  the result of the body trying to conserve fluid. Physiologic age-related changes in salivary gland tissues may lead to a modest reduction in salivary output and partially explain the increased prevalence of xerostomia in older people. [ 1 ]  However,  polypharmacy  is thought to be the major cause in this group, with no significant decreases in salivary flow rate being likely to occur through aging alone. [ 9 ] [ 13 ]


Aside from physiological causes of xerostomia,  iatrogenic  effects of medications are the most common cause. [ 1 ]  A medication which is known to cause xerostomia may be termed  xerogenic . [ 3 ]  Over 400 medications are associated with xerostomia. [ 8 ]  Although drug induced xerostomia is commonly reversible, the conditions for which these medications are prescribed are frequently chronic. [ 8 ]  The likelihood of xerostomia increases in relation to the total number of medications taken, whether the individual medications are xerogenic or not. [ 9 ]  The sensation of dryness usually starts shortly after starting the offending medication or after increasing the dose. [ 1 ]   Anticholinergic ,  sympathomimetic , or  diuretic  drugs are usually responsible. [ 1 ]


Xerostomia may be caused by autoimmune conditions which damage saliva-producing cells. [ 8 ]  Sjögren's syndrome is one such disease, and it is associated with symptoms including fatigue,  myalgia  and  arthralgia . [ 8 ]  The disease is characterised by inflammatory changes in the moisture-producing glands throughout the body, leading to reduced secretions from glands that produce saliva, tears and other secretions throughout the body. [ 8 ]  Primary Sjögren's syndrome is the combination of dry eyes and xerostomia. Secondary Sjögren's syndrome is identical to primary form but with the addition of a combination of other connective tissue disorders such as  systemic lupus erythematosus  or  rheumatoid arthritis . [ 8 ]


Xerostomia may be the only symptom of celiac disease, especially in adults, who often have no obvious digestive symptoms. [ 14 ]


Radiation therapy for  cancers of the head and neck  (including  brachytherapy  for  thyroid cancers ) where the salivary glands are close to or within the field irradiated is another major cause of xerostomia. [ 8 ]  A radiation dose of 52 Gy is sufficient to cause severe salivary dysfunction. Radiotherapy for oral cancers usually involves up to 70 Gy of radiation, often given along with chemotherapy which may also have a damaging effect on saliva production. [ 8 ]  This side effect is a result of radiation damage of the parasympathetic nerves. Formation of salivary gland ducts depends on the secretion of a  neuropeptide  from the parasympathetic nerves, while development of the end buds of the salivary gland depends on  acetylcholine  from the parasympathetic nerves. [ 15 ]


"Sicca" simply means dryness. Sicca syndrome is not a specific condition, and there are varying definitions, but the term can describe oral and eye dryness that is not caused by autoimmune diseases (e.g., Sjögren syndrome).


Oral dryness may also be caused by mouth breathing, [ 3 ]  usually caused by partial obstruction of the  upper respiratory tract . Examples include  hemorrhage ,  vomiting ,  diarrhea , and  fever . [ 1 ] [ 9 ]


Alcohol may be involved in the cause of salivary gland disease, liver disease, or dehydration. [ 3 ]


Smoking is another possible cause. [ 9 ]  Other recreational drugs such as  methamphetamine , [ 16 ]   cannabis , [ 17 ]   hallucinogens , [ 18 ]  or  heroin , [ 19 ]  may be implicated.


Hormonal disorders, such as poorly controlled diabetes, chronic graft versus host disease or low fluid intake in people undergoing  hemodialysis  for renal impairment may also result in xerostomia, due to dehydration. [ 8 ]


Nerve damage can be a cause of oral dryness. An injury to the face or surgery can cause nerve damage to the head and neck area which can effect the nerves that are associated with the salivary flow. [ 20 ]


Xerostomia may be a consequence of infection with hepatitis C virus (HCV) and a rare cause of salivary gland dysfunction may be  sarcoidosis . [ 8 ]


Infection with Human Immunodeficiency Virus/Acquired immunodeficiency Syndrome (AIDS) can cause a related salivary gland disease known as Diffuse Infiltrative Lymphocytosis Syndrome (DILS). [ 8 ]


Similar to taste dysfunction, xerostomia is one of the most prevalent and persistent oral symptoms associated with COVID-19. Despite a close association with COVID-19, xerostomia, dry mouth and hyposalivation tend to be overlooked in COVID-19 patients and survivors, unlike ageusia, dysgeusia and hypogeusia. [ 21 ]


A diagnosis of hyposalivation is based predominantly on the clinical signs and symptoms. [ 1 ]  The  Challacombe scale  maybe used to classify the extent of dryness. [ 22 ] [ 23 ]  The rate of the salivary flow in an individual's mouth can also be measured. [ 24 ]  There is little correlation between symptoms and objective tests of salivary flow, [ 25 ]  such as  sialometry . This test is simple and noninvasive, and involves measurement of all the saliva a patient can produce during a certain time, achieved by dribbling into a container. Sialometery can yield measures of stimulated salivary flow or unstimulated salivary flow. Stimulated salivary flow rate is calculated using a stimulant such as 10%  citric acid  dropped onto the tongue, and collection of all the saliva that flows from one of the  parotid papillae  over five or ten minutes. Unstimulated whole saliva flow rate more closely correlates with symptoms of xerostomia than stimulated salivary flow rate. [ 1 ]   Sialography  involves introduction of  radio-opaque  dye such as  iodine  into the duct of a salivary gland. [ 1 ]  It may show blockage of a duct due to a calculus. Salivary  scintiscanning  using  technetium  is rarely used. Other medical imaging that may be involved in the investigation include  chest x-ray  (to exclude sarcoidosis),  ultrasonography  and  magnetic resonance imaging  (to exclude Sjögren's syndrome or neoplasia). [ 1 ]  A minor salivary gland  biopsy , usually taken from the lip, [ 26 ]  may be carried out if there is a suspicion of  organic disease  of the salivary glands. [ 1 ]   Blood tests  and  urinalysis  may be involved to exclude a number of possible causes. [ 1 ]  To investigate xerophthalmia, the Schirmer test of lacrimal flow may be indicated. [ 1 ]   Slit-lamp examination  may also be carried out. [ 1 ]


The successful treatment of xerostomia is difficult to achieve and often unsatisfactory. [ 9 ]  This involves finding any correctable cause and removing it if possible, but in many cases it is not possible to correct the xerostomia itself, and treatment is  symptomatic , and also focuses on  preventing tooth decay through improving  oral hygiene . Where the symptom is caused by hyposalivation secondary to underlying chronic disease, xerostomia can be considered permanent or even progressive. [ 8 ]  The management of salivary gland dysfunction may involve the use of saliva substitutes and/or saliva stimulants:


Saliva substitutes can improve xerostomia, but tend not to improve the other problems associated with salivary gland dysfunction. [ citation needed ]  Parasympathomimetic drugs (saliva stimulants) such as pilocarpine may improve xerostomia symptoms and other problems associated with salivary gland dysfunction, but the evidence for treatment of radiation-induced xerostomia is limited. [ 27 ]  Both stimulants and substitutes relieve symptoms to some extent. [ 28 ]   Salivary stimulants are probably only useful in people with some remaining detectable salivary function. [ 3 ]  A systematic review compromising of 36  randomised controlled trials  for the treatment of dry mouth found that there was no strong evidence to suggest that a specific  topical  therapy is effective. [ 8 ]  This review also states that topical therapies can be expected to provide only short-term effects, which are reversible. [ 8 ]  The review reported limited evidence that oxygenated glycerol triester spray was more effective than electrolyte sprays. [ 8 ]  Sugar free  chewing gum  increases saliva production but there is no strong evidence that it improves symptoms. [ 8 ]   Plus, there is no clear evidence to suggest whether chewing gum is more or less effective as a treatment. [ 8 ]  There is a suggestion that intraoral devices and integrated mouthcare systems may be effective in reducing symptoms, but there was a lack of strong evidence. [ 8 ]  A systematic review of the management of radiotherapy-induced xerostomia with parasympathomimetic drugs found that there was limited evidence to support the use of pilocarpine in the treatment of radiation-induced salivary gland dysfunction. [ 6 ]  It was suggested that, barring any  contraindications , a trial of the drug be offered in the above group (at a dose of five mg three times per day to minimize side effects). [ 6 ]  Improvements can take up to twelve weeks. [ 6 ]  However, pilocarpine is not always successful in improving xerostomia symptoms. [ 6 ]  The review also concluded that there was little evidence to support the use of other parasympathomimetics in this group. [ 6 ]  Another systematic review showed, that there is some low-quality evidence to suggest that amifostine prevents the feeling of dry mouth or reduce the risk of moderate to severe xerostomia in people receiving radiotherapy to the head and neck (with or without chemotherapy) in the short- (end of radiotherapy) to medium-term (three months postradiotherapy). But, it is less clear whether or not this effect is sustained to 12 months postradiotherapy. [ 29 ]


A 2013 review looking at non-pharmacological interventions reported a lack of evidence to support the effects of electrostimulation devices, or acupuncture, on symptoms of dry mouth. [ 30 ]


Xerostomia is a very common symptom. A conservative estimate of prevalence is about 20% in the general population, with increased prevalences in females (up to 30%) and the elderly (up to 50%). [ 8 ]  Estimates of the prevalence of persistent dry mouth vary between 10 and 50%. [ 8 ]


Xerostomia has been used as a test to detect lies, which relied on emotional inhibition of salivary secretions to indicate possible incrimination. [ 31 ]


ATC code D   Dermatologicals  is a section of the  Anatomical Therapeutic Chemical Classification System , a system of alphanumeric codes developed by the  World Health Organization  (WHO) for the classification of  drugs  and other medical products. [ 1 ] [ 2 ] [ 3 ] [ 4 ]


Codes for  veterinary  use ( ATCvet codes ) can be created by placing the letter Q in front of the human ATC code: for example,  QD . [ 5 ]  ATCvet codes without corresponding human ATC codes are cited with the leading Q in the following list. National issues of the ATC classification may include additional codes not present in this list, which follows the WHO version.


Aluminium triacetate , formally named  aluminium acetate , [ 2 ]  is a  chemical compound  with composition  Al(CH 3 CO 2 ) 3 .  Under  standard conditions  it appears as a white,  water -soluble solid [ 1 ]  that decomposes on heating at around 200 °C. [ 3 ]   The triacetate  hydrolyses  to a mixture of basic hydroxide /  acetate   salts , [ 4 ]  and multiple species co-exist in  chemical equilibrium , particularly in aqueous solutions of the acetate ion; the name aluminium acetate is commonly used for this mixed system.


It has therapeutic applications for its anti-itching,  astringent , and  antiseptic  properties, [ 5 ]  and, as an  over-the-counter preparation  like  Burow's solution , [ 6 ]  it is used to treat  ear infections . [ 7 ] [ 8 ]  Burow's solution preparations have been diluted and modified with  amino acids  to make them more  palatable  for use as  gargles  for conditions like  aphthous ulcers  of the mouth. [ 9 ]   In  veterinary medicine , aluminium triacetate's astringency property is used for treating  Mortellaro disease  in hoofed animals such as cattle. [ 10 ]


Aluminium triacetate is used as a  mordant  agent with dyes like  alizarin , [ 11 ]  both alone and in combination. Together with  aluminium diacetate [ 12 ]  or with  aluminium sulfacetate [ 13 ]  it is used with  cotton , other  cellulose  fibres, [ 14 ]  and  silk . [ 13 ]   It has also been combined with  ferrous acetate  to produce different colours. [ 15 ]


According to the  formal rules for naming inorganic compounds , the name for  Al(CH 3 CO 2 ) 3  is aluminium acetate, [ 2 ]  though more formal names like aluminium(III) acetate and aluminium ethanoate are acceptable. [ 4 ]   The use of the "tri" multiplying prefix in the name aluminium triacetate, while not technically required, is regularly used to avoid potential confusion with related compounds with  hydroxo ligands .  Basic  aluminium diacetate , formally hydroxyaluminium diacetate ( CAS RN  142-03-0), [ 1 ]  has composition  HOAl(CH 3 CO 2 ) 2  with one hydroxo ligand in place of an acetate ligand, and dibasic  aluminium monoacetate , formally dihydroxyaluminium acetate (CAS RN 7360-44-3), has composition  (HO) 2 AlCH 3 CO 2  with only one acetate ligand.  These three compounds are distinct in the solid phase but are usually treated as a group and described collectively as aluminium acetate in solution, due to the triacetate  hydrolyzing  to a mixture which includes the other two forms. [ 4 ]   The abbreviation as AlAc, along with variants like  AlAc 2+  and  AlAc + 2 , are sometimes used in the discipline of  geochemistry , [ 16 ]  though these are inconsistent with standard practice in mainstream  chemistry . [a]


The formula  Al(CH 3 CO 2 ) 3  indicates the presence of aluminium centres in the +3  oxidation state  and  acetate  groups in a ratio of 1:3. Images used to represent this substance, such as those shown at left, represent two highly oversimplified approximations of the solid-state structure: the first is as a purely  ionic   salt  with a single aluminium(III)  cation  (Al 3+ ) surrounded by and associated  electrostatically  with three acetate anions ( CH 3 CO − 2 ), but this should not be taken to convey information about the  crystal structure . For example, sodium chloride (NaCl) has a cation-to-anion  stoichiometry  of 1:1, but it has a  cubic structure  with each ion surrounded  octahedrally  by six ions of the opposite charge. [ 17 ]


The other image is a  molecular  form with the three acetate groups  covalently bonded  to the metal centre in a  trigonal planar  geometry and  intermolecular interactions  holding the molecules together with each other in the crystal structure.  It is highly likely that the solid state structure is more complicated and includes both covalent and ionic characteristics and it is possible that multiple aluminium centres and / or  bridging acetate  groups might be present – both of these have been reported in aluminium acetate  solution [ 18 ]  and  aluminium chloride  is known to exist as a  Al 2 Cl 6   dimer . [ 19 ]


NMR  investigations of the aqueous aluminium(III) / acetate system show the presence of aluminium as a hexaaqua  complex ,  [Al(H 2 O) 6 ] 3+ , [ 20 ]  as well as mononuclear species with different substitutions. In addition, the investigations demonstrate that a significant solution-phase species is an  Al 13   tridecamer , [ 21 ]  a  moiety  reported in conflicting mechanisms of hydrolysis and  polymerisation  aluminium solutions. [ 22 ]   Other trivalent metal cations are known to form polynuclear species:  iron(III) acetate , for example, forms a trinuclear structure [ 23 ]  with a triply-bridged oxo centre [ 24 ]  with the cation  [Fe 3 ( μ 3 –O)(OAc) 6 (H 2 O) 3 ] + . [ 25 ]   The compound  chromium acetate hydroxide , Cr 3 (OH) 2 (OAc) 7 , has also been described as isostructural. [ 26 ]   Analogous  ruthenium(III), vanadium(III), rhodium(III), and iridium(III) compounds with trinuclear structures are known. [ 27 ]   Copper(II) acetate  and  chromium(II) acetate  both have dinuclear dihydrate structures, M 2 (OAc) 4 (H 2 O) 2 , [ 28 ]  as does  rhodium(II) acetate ; [ 29 ]  each shows significant metal-metal bonding interactions. [ 28 ] [ 29 ]


According to the  CRC Handbook of Inorganic Compounds,  aluminium triacetate is a white, water-soluble solid and is usually prepared from  aluminium chloride  or directly from  aluminium  by heating in an  acetic acid  solution with  acetic anhydride . [ 1 ]


Theoretically all of the aluminium / acetate / hydroxide  salts  can be prepared from  aluminium hydroxide  or  sodium aluminate  and acetic acid, but formation of the triacetate only occurs in the absence of water. [ 4 ]     In solutions, the diacetate is the major product formed, and is also produced when aluminium chloride is treated with a  sodium acetate  solution in basic conditions. [ 30 ]   The equations for these processes are:


An improved process using a combination of  aluminium chloride  and sodium aluminate with sodium acetate prepared  in situ  has been  patented : [ 31 ]


The  mordants  aluminium triacetate and  aluminium sulfacetate  can be prepared from  aluminium sulfate , the product formed being determined by the amount of  lead(II) acetate  used: [ 13 ]


On heating, aluminium triacetate decomposes above 200 °C in a process similar to that of  aluminium formate . [ 3 ]   The process begins with loss of acetic anhydride ( Ac 2 O ) between 120 and 140 °C [ 1 ]  to form the a mixture of the basic oxide acetates such as  Al 2 O(CH 3 CO 2 ) 4  and  Al 3 O(CH 3 CO 2 ) 7 , [ 30 ]  which are ultimately transformed to  Al 2 O 3  ( alumina ), first as an  amorphous   anhydrous  solid and then through other solid  phases  (γ-, δ-, and θ-  crystal forms ) to ultimately become  polymorphic  α- Al 2 O 3 : [ 3 ]


Aluminium triacetate hydrolyses to produce both the mono- and di-basic hydroxide acetates in solution or by  hygroscopy : [ 4 ]


According to the  National Cancer Institute , the aluminium acetates are used  topically  in humans as  antiseptic agents , which also cause  body tissues to shrink . [ 5 ]   Its astringency property is also used for treating  Mortellaro disease  in hoofed animals such as cattle. [ 10 ]   Aluminium acetate promotes healing of  infected skin  and also assists with  inflammation ,  itching , and stinging. [ 5 ]   The  Food and Drug Administration  has approved it for use for "temporary relief of minor skin irritations due to ... ' poison ivy ,' 'poison oak,' ' poison sumac ,' 'insect bites,' ' athlete's foot ,' or 'rashes caused by soaps, detergents, cosmetics, or jewelry.'" [ 32 ]   For these applications,  over-the-counter preparations  such as  Burow's solution  are typically used, [ 6 ]  while diluted forms are used as  gargles  for conditions like  aphthous ulcers  of the mouth, including with  amino acid  additives to improve  palatability  and  taste . [ 9 ]   The most common use of Burow's solution is in treating  ear infections [ 7 ] [ 8 ]  including  otomycosis , though it is generally not as effective as  clotrimazole  in these fungal infections. [ 33 ]   Topical astringent powder Domeboro contains  aluminium sulfate tetradecahydrate ,  [Al(H 2 O) 6 ] 2 (SO 4 ) 3 •2H 2 O , and  calcium acetate monohydrate ,  Ca(CH 3 CO 2 ) 2 •H 2 O , and forms an aluminium acetate solution similar to Burow's solution when dissolved. [ 34 ]   Domeboro solutions in warm water can be used in cases of  ingrown toenails , [ 35 ]  to reduce irritation and contain any infection which might be present.


A mordant is a substance used to set  dyes  on fabrics or tissue sections by forming a  coordination complex  with the dye, which subsequently attaches to the fabric or tissue. [ 37 ]   A mordant often contains a  polyvalent  metal ion, commonly aluminium or iron, [ 38 ]  as is the case with mixtures of aluminium triacetate with aluminium sulfacetate [ 13 ]  or with basic aluminium diacetate. [ 12 ]   Aluminium triacetate mordants have been used with  cotton , other  cellulose -based fibres, [ 14 ]  and  silk . [ 13 ]   They have also been combined with  ferrous acetate  to produce different colours. [ 15 ]


In the case of the dye  alizarin  (1,2-dihydroxy anthraquinone ,  H 2 Az ), mordanting was hypothesised to involve the formation of a dianion of alizarin. This would form a five-coordinate aluminium complex,  CaAl(OH)Az 2 , [ 39 ]  which can take up water to form a hydrate with a six-coordinate aluminium-centred dianion,  Ca[Al(H 2 O)(OH)Az 2 ]•2H 2 O . [ 40 ]   The proposal was based on  infrared spectroscopic  data, and was subsequently challenged by work suggesting a structure with two bridging hydroxyl ligands connecting a dinuclear core,  Az 2 Al(μ-OH) 2 AlAz 4− 2 , with two alizarin  moieties  each  chelating  to each aluminium centre. [ 36 ]  The structure was proposed by Soubayrol  et al.  based on  27 Al NMR spectroscopy and  electrospray ionisation   mass spectrometry  evidence. [ 41 ]   They reported that the degree of hydration was dependent on the identity of the counter-ion, with the sodium salt being a stable tetrahydrate with a monohydrate being formed from  potassium hydroxide . These were distinguishable based on their  chemical shifts , suggesting the waters are associating with the aluminium centres or the alizarin moieties, and not behaving as is typical for  waters of crystallisation . [ 41 ]


A related structure with calcium ions was reported in 1994, and in it the alizarins chelate to the calcium ions to form AzCaAz bridges between the aluminium centres (which are also bridged by hydroxo groups) and the aluminium centres subsequently bind to the deprotonated  phenol  residues of the dye; [ 11 ]  in the Soubayrol model, each alizarin is associated with a single aluminium cation. [ 41 ]   As with the structure of aluminium acetate itself, the forms it takes in applications has not been resolved.


a   This "Ac" is not referring to the element  actinium .  Used in this way, the convention in  organic chemistry  is for Ac to refer to the  acetyl  group, the  radical  form of which is  CH 3 CO , [ 42 ]  and OAc or AcO would be used for the  acetate  radical,  CH 3 CO 2 , [ 43 ]  sometimes also called "acetoxy."  The acetate ion would then be AcO − ,  CH 3 CO − 2 , and acetic acid would be AcOH or HOAc.  Under this convention, aluminium triacetate would be Al(OAc) 3 .  Publications in  geochemistry , however, are using Ac to refer to acetate rather than acetyl and thus  AlAc + 2  in geochemistry would be written under more usual chemistry conventions as  [Al(OAc) 2 ] +  or  [Al(CH 3 CO 2 ) 2 ] + .


Araroba powder , also known as  Bahia powder  and  Goa powder , is a drug occurring in the form of a yellowish-brown powder, varying considerably in tint, from the  Portuguese  colony of  Goa , where it appears to have been introduced about the year 1852. [ 1 ] [ 2 ]


The tree which yields it is the  Andira araroba  of the  family   Fabaceae . It is abundant in certain forests in the province of  Bahia  in Brazil as well as imported into India, preferring as a rule low and humid spots. The tree ranges from 80 to 100 ft. high and has large  imparipinnate , or feather shaped, leaves, the leaflets of which are oblong, about 12 in. long and 1 in. broad, and somewhat truncate at the apex. The flowers are  papilionaceous , of a purple color and arranged in  panicles . [ 1 ]


The Goa powder or araroba is contained in the trunk, filling crevices in the  heartwood . It is a morbid product in the tree, and yields to hot chloroform 50% of a substance known officially as  chrysarobin . It occurs as a  microcrystalline , odorless, tasteless powder, very slightly soluble in either water or alcohol; it also occurs in  rhubarb  root. This complex mixture contains pure chrysarobin, di-chrysarobin, and di-chrysarobin methylether. Chrysarobin is a  methyl trioxyanthracene  and exists as a  glucoside  in the plant, but is gradually  oxidized  to  chrysophanic acid  (a dioxy-methyl  anthraquinone ) and  glucose . This strikes a blood-red color in  alkaline  solutions, and may therefore cause much alarm if administered to a patient whose urine is alkaline. [ 1 ]


Dithranol  and  chrysophanic acid  are therapeutic substances in araroba powder that are responsible for success in treatment of  psoriasis  and chronic  eczema . [ 3 ]  It has been used as a treatment of  ringworm . Generally, when used for skin conditions, the powder is mixed into a zinc or petrolatum  ointment ,  paste , or  cream  base to contain it to the treatment area. [ 4 ]  The  British Pharmacopoeia  lists an ointment containing one part of chrysarobin and 24 parts of  benzoated   lard . [ 1 ]  The drug is a weak  antiparasitic .


Araroba powder stains skin, hair, and clothing a deep yellow or brown, a coloration which may be removed by caustic alkali in weak solution. [ 1 ]  Both internally and externally the drug is a powerful irritant. Reported  adverse effects  include inflammation of the  eyes ,  gastrointestinal tract , and  kidneys .  Contact allergy  has also been reported. [ 5 ] [ 6 ]


The  mechanism of action  of araroba powder is not yet confirmed, but is believed to effect  cell turnover .  Anti-inflammatory  properties are also present by  neutrophil  and  monocyte  function inhibition. [ 7 ]


Becaplermin , sold under the brand name  Regranex , is a  cicatrizant , available as a  topical gel .  Regranex is a human  platelet-derived growth factor  indicated along with good wound care for the treatment of lower extremity diabetic neuropathic ulcers. [ 1 ]  It is also known as "platelet-derived growth factor BB". [ 1 ]


Becaplermin is used for the treatment of  diabetic   foot ulcers . [ 2 ]  Studies of becaplermin showed that when used with good wound care, complete healing significantly increased and the ulcers healed on average 6 weeks faster. [ 3 ]  Pharmacoeconomic studies reinforce the cost effectiveness of becaplermin as an adjunct to good wound care. [ 4 ]