Pemphigus vulgaris can occur in any breed of dog irrespective of its sex or age. [ 4 ]  However, it appears to occur more often in male dogs than females, which differs slightly from its occurrence in humans. In humans, women are more likely to be affected than men. In terms of age, the disease usually begins when the dog is at least five to seven years old. This correlates to the typical age in which it begins in humans as well, generally occurring in  middle age . [ 15 ]


Since many autoimmune skin diseases have similar symptoms and usually affect the oral cavity, a biopsy must often be performed in order to correctly diagnose the disease. [ 18 ]  Due to the wide scale of clinical symptoms that can be present, along with the diverse variations of skin autoimmune dermatoses, a single symptom will more than likely not lead to a diagnosis. Instead, the results of the biopsy combined with the canine's history and other clinical signs can help in confirming the diagnosis of the disease. Breed predisposition and the age of the dog can also be indications of the various possibilities of autoimmune skin diseases. [ 19 ]  Some common symptoms that can be used to lead to a confirmed diagnosis include alopecia, crusting, ulcerations, vasculitis, and many more. [ 19 ]


Histopathology evaluations can be done by extracting areas of the skin that show indications of being affected, such as taking biopsies of lesions, pustules, and sites of crustation. These tissue samples would then be typically examined under a microscope, where a clinician will form a conclusive diagnosis based on the observed cellular structures and abnormalities. [ 19 ]  Additionally, other tests such as antinuclear antibody tests (ANA) and complete blood count with white blood cell differential tests can be used to gather more information. [ 20 ]


For Pemphigus vulgaris, after the skin begins to separate,  Nikolsky's sign  can be useful to help diagnose the disease. This involves placing pressure along the edge of a blister and observing if the skin separates further and if the blister increases in size. [ 21 ]  However, to diagnose the disease with complete certainty, biopsies must be taken from the edge of the blisters. The tissue sample must then be analyzed using a direct  immunofluorescence  technique and analyzed  microscopically . The direct immunofluorescence technique should be used instead of indirect, as the results may be inaccurate before the disease has progressed to a certain point. [ 4 ]


For most autoimmune skin diseases, it is imperative to begin treatment as early as possible, as the progression of the disease can lead to severe complications and even death. [ 4 ]  Treatment for many diseases usually involves the use of  immunosuppressants  such as  glucocorticoids . [ 18 ]  The immunosuppressants aid in suppressing the reaction of the immune system fighting against the body's healthy cells and tissues. [ 22 ]  This is done by the inhibition of calcineurin, an enzyme that controls and activates T-cell production. Without the consistent production of T-cells, a decrease of autoimmune activity can be observed, leading to less severe symptoms and potential remission of autoimmune diseases. [ 23 ]


When treatment is first started for Pemphigus vulgaris, the dog will usually be given the  corticosteroid   prednisone  for a limited time. This will be administered orally, and the amount given can vary between 1.5 and 13.3  milligrams  for every  kilogram  of the dog's weight. This amount will continue until symptoms begin to subside. Afterward the dose will be lowered, and other medications will be used. The condition cannot be cured, so the dog will require immunosuppressants and  steroids  for the duration of its lifespan. The specific immunosuppressants used generally include  cyclophosphamide ,  methotrexate , or  azathioprine .  Antibiotics  may also be used to help reduce the risk of infection. [ 4 ]


Balanitis circinata  (also known as  circinate balanitis ) is a skin condition comprising a  serpiginous  ring-shaped  dermatitis  of the  glans penis . [ 1 ]  While circinate balanitis is one of the most common cutaneous manifestations of reactive arthritis, it can also occur independently.  Topical corticosteroid  therapy is the most commonly used treatment, and topical  calcineurin inhibitors  have also been used successfully. [ 2 ]


At the first stages of the condition, patients show pinhead-sized lesions covered by white plaque, which grow into a flat, red region with a white margin. Despite the visible symptoms, patients rarely suffer from  burning  or  itching , and the lesions rarely smell strange. [ 3 ]  Due to its visual appearance, balanitis circinata is often misdiagnosed as a  fungal infection , especially in those that have no other symptoms of  reactive arthritis . [ citation needed ]


Reactive arthritis  is characterized by  nongonococcal urethritis ,  conjunctivitis , and  arthritis . Reactive arthritis belongs to the group of arthritides known as the spondyloarthritides. There are two main types of reactive arthritis: post-venereal and post-enteric.  Chlamydia trachomatis  is thought to be the most common cause of reactive arthritis, in general. Until recently, even the terminology for the condition itself was unclear as multiple eponyms and names have been associated with reactive arthritis. In recent years, a great deal has been learnt about the epidemiology, pathophysiology and treatment of reactive arthritis and chlamydia-induced reactive arthritis, specifically. Prospective epidemiologic data suggest that chlamydia-induced reactive arthritis is underdiagnosed. Other truths being actively revealed include data suggesting that the pathogen itself (i.e., chlamydia) might play an equally important role, or perhaps even more important, than the host with disease susceptibility; asymptomatic chlamydial infections might be a common cause of reactive arthritis and the two variants of reactive arthritis might respond differently to treatment in spite of the congruent clinical presentation. However, much about this syndrome remains shrouded in mystery. Recent data has been suggesting that Chlamydia-induced reactive arthritis might be a common condition that clinicians are simply failing to recognise. Therefore, an emphasis is placed on disease awareness since viable treatment options are emerging. [ 4 ]


Balanitis circinata is one out of multiple manifestations of the reactive arthritis.  [ citation needed ]


Right now,  topical corticosteroid  therapy is the most commonly used treatment, and topical  calcineurin inhibitors  have also been used successfully. [ 2 ]
Newer tests on patients showed that a less harmful  off-label  topical treatment with the  immunomodulator   pimecrolimus  or the  immunosuppressant   tacrolimus  can prevent all visible symptoms of this disease. [ citation needed ]  Since reactive arthritis cannot be healed as such, affected people are forced to a continuous topical treatment – otherwise they will again note first symptoms after three to four days without it.  [ citation needed ]


However, strong debates and controversies continue regarding the exact indications of immunomodulators like pimecrolimus and their duration of use in the absence of active controlled trials. [ 5 ]  A study released in 2015 (tested were 7,457 children with a total of 26,792 person-years) did not find any evidence that pimecrolimus could cause cancer. [ 6 ]


BPAg1  is an antigen found in human skin.  This antigen should not be confused with  BPAg2 .


Cellular angiofibroma  ( CAF ) is a rare,  benign tumor  of superficial  soft tissues  that was first described by M. R. Nucci et al. in 1997. [ 1 ]  These tumors occur predominantly in the distal parts of the  female  and  male reproductive systems , i.e. in the  vulva - vaginal  and  inguinal - scrotal  areas, respectively, or, less commonly, in various other superficial soft tissue areas throughout the body. [ 2 ]  CAF tumors develop exclusively in adults who typically are more than 30 years old. [ 3 ]


CAF tumors are composed of bland  mesenchymal [ 4 ]  spindle-shaped cells in an edematous (i.e. abnormally swollen with fluid) to fiber-laded connective tissue background. [ 2 ]  Mesenchymal cells are cells in the  cell lineage  that includes  fibroblasts ,  adipocytes  (i.e. fat cells),  macrophages ,  mast cells ,  leucocytes , and the precursor cells which mature into these cell types. In 2020, the World Health Organization classified cellular angiofibroma tumors in the category of benign  fibroblastic and myofibroblastic tumors . [ 5 ]


CAF tumors rarely recur after surgical removal [ 3 ]  and do not  metastasize  to distant tissues. [ 5 ]  Accordingly,  surgical resection is the commonly performed and current standard for treating these tumors. [ 6 ]


CAF tumors commonly present as painless, slowly growing, soft tissue nodules or masses in the vulva-vaginal and inguinal-scrotal areas; less commonly in the  perineum ; and rarely in the  urethra ,  pelvis ,  anus ,  retroperitoneum ,  lumbar region , middle of the trunk, [ 7 ]   rectum , oral mucosa, knee, upper eyelid, [ 6 ]  hip, chest wall,  axilla , breasts, and upper abdomen. [ 2 ]  The tumors are generally centered in the  subcutaneous tissue [ 4 ]  or in the case of internal tumors, such as those located in the mouth, urethra, rectum, or anus, the  submucosa . [ 6 ]  In one study of 51 individuals, these tumors had been noticed for 1 week to 5 years (median time: 5 months) prior to diagnosis in women (median age: 47 years) and men (median age: 60 years). Their tumors ranged from 0.6 to 25.0 cm in maximum diameter size (median size 2.7 cm in women and 6.7 cm in men). [ 7 ]


Grossly , CAF tumors appear as well-circumscribed, firm to rubbery, white/tan to grayish masses some of which appear to consist of multiple   lobules . [ 7 ]  Rarely, these tumors had infiltrated into adjacent muscles or other nearby tissues. [ 3 ]  As determined by  microscopic  analyses, CAF tumors are composed of bland spindle-shaped cells in an edematous to fibrous  stromal  background containing bundles of  collagen  fibers, small to medium-sized, thick-walled, prominently hyalinized (i.e. glassy appearing) blood vessels, and a minor component of  adipose tissue  (i.e. fat tissue). Numerous  mast cells , moderate numbers of  lymphocytes , and small numbers of  neutrophils  are scattered throughout this stroma; this stroma does not contain the  multinucleated giant cells  or  epithelioid cells  that are often found in certain other types of mesenchymal tumors. [ 2 ]  However, CAF lesions may contain scattered, abnormally-shaped cells,  lipoblasts  (i.e. immature fat cells), and diffuse malignant-appearing  sarcoma -like changes but these findings do not alter the prognosis of CAF as being a purely benign tumor. [ 3 ]


Immunohistochemical  analyses find that the cells in CAF tumors express the  CD34  protein in ~50% of cases, a  smooth muscle actin  protein in occasional cases,  MUC1  (also termed EMA) and  desmin  proteins in a minority of cases, but do not express  S100  or  cytokeratin  proteins. [ 3 ] [ 4 ] [ 6 ]  Most cases of CAF in females contain CAF tumor cells which express  estrogen  and  progesterone receptors [ 4 ]  while limited studies in males reported that 3 of 3 CAF cases contained estrogen receptor-expressing tumor cells while only 1 of 3 cases contained progesterone receptor-expressing tumor cells. [ 8 ]  Detection of one or more of these protein expression patterns can help differentiate CAF from other types of mesenchymal tumors. [ 3 ] [ 4 ] [ 6 ]


Fluorescence in situ hybridization  analysis shows that the neoplastic cells in all cases of CAF have a  deletion  in or around   band  14 on the  long (or "q") arm  of one of their two  chromosomes 13 . This results in a loss of one of the two  RB1  genes (located at band 14.2 on the q arm of this chromosome [ 9 ] ) as well as one of the two  FOXO1  genes (located at band 14.11 on the q arm of this chromosome [ 10 ] ). [ 4 ] [ 11 ]  Deletion of one of the  RB1  genes, it is proposed but not yet demonstrated, may act to promote the development and/or progression of CAF tumors. In any event, loss of this gene in one of the two chromosome 13s is extremely helpful for distinguishing CAF from most other mesenchymal tumor types. [ 4 ]


The diagnosis of CAF generally depends on its typical location in vulva-vaginal and inguinal-scrotal areas, spindle-shaped cell histopathology, tumor cell expressions of marker proteins, and absence of one of the two  RP1  genes. CAF can be hard to distinguish from two other spindle-shaped cell tumors,  myofibroblastoma  and  spindle cell lipoma , that commonly also contain tumors cells with deletions in one of their two  RF1  genes. The characteristic hyalinized blood vessels and the presence of CD34 protein-expressing and desmin protein-expressing cells in CAF help to distinguish it from myofibroblastoma. [ 3 ]  Unlike CAF, spindle cell lipomas seldom contain desmin protein-expressing or progesterone receptor-expressing tumor cells [ 3 ]  and commonly contain  CD99 - and S100-expressing proteins. [ 6 ]  In addition, spindle cell lipomas are rare in the vulvovaginal region and their tumor vasculature consists of capillary-sized, thin-walled blood vessels while those of CAF consist of more numerous blood vessels with thick, hyalinized walls. [ 2 ]  CAR and  angiomyofibroblastoma  can be difficult to distinguish from one another but angiomyofibroblastoma tumor cells show no alterations in their  RB1  and  FOXO1  genes. [ 12 ]


The current standard for treating CAF tumors is total surgical resection (i.e. resection that does not leave any residual neoplastic tissue behind). [ 6 ]  This treatment appears adequate (i.e. curative) even in cases were CAF tumors contain atypical cells and/or sarcoma-like histopathology. [ 2 ]  In many reported cases, CAF tumors treated with simple surgical excision or “shelling out” also appeared to have achieved adequate results. [ 4 ]  CAF tumors rarely recur at the sites of their surgical removal whether treated by total or simple resections [ 3 ]  and have not been reported to metastasize. Consequently, the prognosis for CAF is excellent. [ 2 ] [ 4 ]


Centurion syndrome  is characterized by anterior malposition of the medial part of the lid, with displacement of  puncta  out of the  lacus lacrimalis  due to a prominent  nasal bridge . [ 1 ] [ 2 ]


Childhood granulomatous periorificial dermatitis  ( CGPD ) is a rare benign  granulomatous  skin disease of unknown cause. [ 1 ]  The disorder was first described in 1970 by Gianotti in a  case series  of five children. [ 2 ]  CGPD is more common in boys than girls. [ 3 ]


CGPD is characterized by the presence of small, raised, dome-shaped, flesh-colored or yellow-brown  papules  primarily distributed around the mouth, eyes, and nose. [ 1 ]  Affected children may also have papules on the ears, eyelids, cheeks, forehead, and nose. [ 1 ]  CGPD skin lesions rarely affect areas of the skin other than the face. [ 1 ]


The cause of CGPD is unknown. [ 3 ]


The approach to diagnosing CGPD is controversial. [ 2 ]  Certain  dermatologists  suggest that ruling out infectious and allergic causes of similar skin eruptions and a  skin biopsy  demonstrating features consistent with CGPD is adequate for diagnosis. In contrast, other dermatologists advocate for performing a complete history and physical examination and obtaining laboratories and appropriate imaging to rule out cutaneous  sarcoidosis . [ 2 ]  On microscopy, non- tuberculous  granulomas with surrounding  lymphocytes  clustered around hair follicles may be seen; additionally, infiltrates of epithelioid  macrophages , lymphocytes, and  giant cells  may also be seen. [ 2 ] [ 3 ]


Several conditions exhibit skin findings similar to those of CGPD. These conditions include  perioral dermatitis ,  acne vulgaris ,  granulomatous rosacea ,  contact dermatitis ,  folliculitis ,  atopic dermatitis ,  cheilitis , medication-induced  acneiform  eruptions,  lupus miliaris disseminatus faciei ,  benign cephalic histiocytosis ,  granulosis rubra nasi ,  xanthomas ,  zinc deficiency ,  glucagonoma , cutaneous  sarcoidosis , and  scabies . [ 2 ] [ 3 ]


Treatment recommendations for CGPD vary and may include observation without treatment, stopping the use of topical corticosteroids, and the use of topical or oral antibiotics as well as  isotretinoin . [ 2 ]  Topical antibiotics such as  metronidazole  and  erythromycin  have been used for CGPD. [ 2 ]  Oral antibiotics of the  tetracycline  class such as  minocycline ,  doxycycline , and tetracycline have been recommended for CGPD. [ 1 ]   Trimethoprim/sulfamethoxazole  has also been used. [ 2 ]  The use of oral systemic antibiotics is limited by side effects such as  nausea ,  vomiting , and  sensitivity of the skin to sunlight . [ 1 ]  Tetracycline antibiotics are not recommended for children under the age of 8 since tetracyclines are known to deposit in teeth (thereby staining them) and impair bone growth in children. [ 1 ]


The use of  calcineurin inhibitor  creams such as  tacrolimus  or  pimecrolimus  on the skin is controversial and results have been mixed. [ 1 ]  Certain studies found the use of topical calcineurin inhibitors led to resolution of CGPD whereas others saw incomplete resolution or prolonged symptoms. [ 1 ]  Topical  azelaic acid  has been used successfully to treat CGPD. [ 1 ]  Immediate discontinuation of topical  corticosteroids  is recommended since corticosteroids are thought to worsen CGPD. [ 2 ]


CGPD is known to be a temporary skin disease with a benign course. [ 1 ]  The skin papules typically resolve after a few months to a few years. After CGPD resolves, the skin may return to normal without scarring or may have small  atrophic  depressions with  collagen loss ,  milia , or small pit-like scars. [ 1 ]


CGPD occurs most often in children of  Afro-Caribbean  descent  before  puberty  though reports of this disease occurring in  Asian  and  Caucasian  children have also been described. [ 1 ] [ 3 ]  Due to the limited number of reported cases, it remains controversial whether CGPD occurs more often in African children than in children of other races. [ 2 ]  CGPD is more common in boys than girls. [ 3 ]


Gianotti et al. first described CGPD in five Italian children in 1970. [ 3 ]  In 1990, Williams et al. described a similar skin eruption in five children of Afro-Caribbean descent and coined the proposed term "facial Afro-Caribbean childhood eruption (FACE)". [ 3 ]  Subsequently, another article by Katz and Lesher first introduced the term CGPD since some reported cases were not found in children of Afro-Caribbean descent and to avoid confusion with perioral dermatitis. [ 3 ]


A number of diseases/syndromes of the human body may be associated with the development of  café au lait macules .


Corticosteroid-induced lipodystrophy  ( CIL ) is a condition of  abnormal fat deposition  caused by  corticosteroid  medications. [ 1 ]  Fat accumulates in the facial area (" moon face "), dorsocervical region ("buffalo hump"), and abdominal area ("pot belly" or "beer belly"), whereas the thickness of  subcutaneous fat  in the limbs is decreased. [ 1 ]  The resulting appearance has been described as "Cushingoid", [ 1 ]  in relation to the fact that it also occurs in individuals with  Cushing's syndrome  (abnormally high  cortisol  levels). [ 2 ]  The condition is considered by patients to be the most distressing side effect caused by corticosteroids. [ 1 ]


Short-term therapy (<3 months) with 10 to 30 mg/day of a  prednisone  equivalent has been reported to be associated with Cushingoid traits in 15 to 40%. [ 1 ]  Long-term therapy (>3 months) with corticosteroids has been associated with Cushingoid features in 32 to 83% of individuals. [ 1 ]  However, these symptoms have mostly been diagnosed in a subjective and observer-dependent manner. [ 1 ]  In a prospective study, the cumulative incidence of CIL with high-dose prednisone therapy was found to be 61% after 3 months, 65% after 6 months, 68% after 9 months, and 69% after 12 months. [ 1 ]  One study found that even a very low dosage of prednisone of 5 mg/day was associated with symptoms of "Cushing's syndrome". [ 1 ]  It has been said that data on risk factors for CIL, such as corticosteroid dosage or duration of therapy, is surprisingly sparse. [ 1 ]  Possible risk factors for CIL include high residual cortisol secretion, decreased clearance of corticosteroids, female sex, younger age (<50 years), high initial  body-mass index , and high  caloric intake . [ 1 ]


CIL has been found to be usually reversible at prednisone-equivalent dosages of less than 10 mg/day. [ 1 ]  A  low-calorie diet  may be considered to limit the risk of CIL or to attempt to reverse it. [ 1 ]  CIL is not merely an aesthetic adverse effect, as it has been associated with features of  metabolic syndrome  such as  insulin resistance ,  dyslipidemia , and  high blood pressure . [ 1 ]


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


Cutaneous amoebiasis ,  refers to a form of  amoebiasis  that presents primarily in the skin. It can be caused by  Acanthamoeba [ 2 ] [ 3 ]  or  Entamoeba histolytica . [ 4 ] : 421  [ 5 ]  When associated with  Acanthamoeba , it is also known as "cutaneous acanthamoebiasis". [ 6 ]   Balamuthia mandrillaris  can also cause cutaneous amoebiasis, but can prove fatal if the amoeba enters the bloodstream  [ 7 ] [ 8 ]


It is characterized by  ulcers . Diagnosis of amebiasis cutis calls for high degree of clinical suspicion. This needs to be backed with demonstration of  trophozoites  from lesions. Unless an early diagnosis can be made such patients can develop significant morbidity. [ 9 ]


This infection-related cutaneous condition article is a  stub . You can help Wikipedia by  expanding it .


Cutaneous manifestations of COVID-19  are characteristic signs or symptoms of the  Coronavirus disease 2019  that occur in the skin. The  American Academy of Dermatology  reports that skin lesions such as  morbilliform  (measles-like rashes, 22%),  pernio  (capillary damage, 18%),  urticaria  (hives, 16%), macular  erythema  (rose-colored rash, 13%), vesicular  purpura  (purplish discolouration, 11%), papulosquamous purpura (discolouration with scale. 9.9%) and  retiform purpura  (blood vessel obstruction and downstream ischaemia, 6.4%) are seen in people with COVID-19. [ 1 ] [ 2 ] [ 3 ]  Pernio-like lesions were more common in mild disease while  retiform purpura  was seen only in critically ill patients. [ 1 ]  The major dermatologic patterns identified in individuals with COVID-19 are urticarial rash, confluent  erythematous / morbilliform  rash,  papulovesicular   exanthem ,  chilbain -like acral pattern,  livedo reticularis  and purpuric "vasculitic" pattern. [ 4 ]   Chilblains  and  Multisystem inflammatory syndrome  in children are also cutaneous manifestations of COVID-19. [ 5 ]


Hyperactive immune responses in COVID-19 patients can contribute to the induction " cytokine storm " (in particular,  IL-6 ); these cytokines could enter the skin and trigger dermal  dendritic cells ,  lymphocytes ,  macrophages ,  mast cells , and  neutrophils , and can assist in the development of lesions such as  maculopapular rash . This representation of cutaneous lesion has been described earlier in diseases having an overactive immune response and excessive cytokine release (example,  systemic lupus erythematosus , adult  Still's disease , and  antiphospholipid syndrome ). [ 6 ]


Urticarial rash  (hives) is seen in several bacterial and viral infections, so COVID-19 is no exception. These rashes are more commonly found in the trunk and limbs, relatively sparing the acral sites. Systemic  corticosteroids  are a therapeutic option for urticarial rash induced by COVID-19. [ 4 ]


The  erythematous rashes  (redness caused by increased blood flow through skin capillaries) seen in COVID-19 are mostly present on the trunk and limbs, and associated with itching. [ 4 ]  Exanthems induced by viruses other than COVID-19 and drug reactions should be considered as differential diagnosis in the case of erythematous rashes. [ 4 ]


Livedo reticularis  refers to slowing of blood flow, leading to desaturation of blood and bluish discolouration of the skin. This type of skin rashes may be seen in cold-induced  vasoconstriction  as seen in  polycythemia  or other causes leading up to focal impairment of blood flow. [ 4 ]


From the  histological  (microscopic anatomy) perspective, several features of the  maculopapular  lesion have been recognized. Maculopapular lesions exhibit superficial perivascular dermatitis with lymphocytic infiltrate and dilated vessels in the papillary and mid dermis with neutrophils, eosinophils, and nuclear debris. Epidermis revealed dispersed foci of hydropic changes, accompanied by minimum  acanthosis ,  subcorneal pustules , slight  spongiosis ,  Basal cell   vacuolation , and foci of  parakeratosis . [ 6 ]  A  lichenoid  pattern with eosinophils' presence on biopsy of skin lesions has been observed in some patients. [ 7 ]


Many cutaneous  neoplasms  occur in the setting of systemic syndromes.


J Am Acad Dermatol. 1983 May;8(5):639-44.
Pilomatricoma-like changes in the epidermal cysts of Gardner's syndrome.
Cooper PH, Fechner RE.


Many conditions of or affecting the human integumentary system have associated abnormalities of the  teeth .


Dermatoosteolysis, Kirghizian type  is a rare presumably autosomal recessive [ 2 ]   genetic disorder  characterized by the infancy-onset recurrence of the following symptoms: cutaneous ulcers, generalized  arthralgia , fevers, peri-articular fistulous osteolysis,  agenesis of all teeth , dystrophied nails, and keratitis. It usually decreases in severity around childhood but around that time complications have already developed, this includes skin scarring,  arthroses , pseudo-acromegalic hands and feet,  scoliosis , and  vision loss . [ 3 ] [ 4 ]  It has been described in 5 siblings born to healthy parents in  Kyrgyzstan . [ 5 ] [ 6 ]


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


In  pathology ,  dermatopathic lymphadenopathy ,  is  lymph node  pathology due to skin disease.


Also known as lipomelanotic reticulosis or Pautrier-Woringer disease, represents a rare form of benign lymphatic hyperplasia associated with most exfoliative or eczematoid inflammatory erythrodermas, including pemphigus, psoriasis, eczema, neurodermatitis, and atrophia senilis.


Dermatopathic lymphadenopathy is diagnosed by a  lymph node  biopsy.  It has a characteristic pattern of  histomorphology  and  immunohistochemical staining :


The treatment is based on the underlying cause.


Dolichonychia  is a medical condition in which the  nail beds  of the fingers and toes are abnormally long and slender, specifically, a finger nail index of 1.30 or more, [ 1 ]  it is a common feature in people with  connective tissue  disorders, such as  Ehlers–Danlos syndromes ,  Marfan syndrome , and  hypohidrotic ectodermal dysplasia ., [ 2 ]  it often appears alongside  arachnodactyly  and/or  dolichostenomelia , which is the condition of having long and slender fingers and toes.


An  eschar  ( / ˈ ɛ s k ɑːr / ;  Greek :  ἐσχάρᾱ ,  romanized :  eskhara ;  Latin :  eschara ) is a slough [ 1 ]  or piece of  dead tissue  that is cast off from the surface of the skin, particularly after a   burn injury , but also seen in  gangrene ,  ulcer ,  fungal infections ,  necrotizing spider bite wounds ,  tick bites  associated with  spotted fevers  and exposure to cutaneous  anthrax . The term ‘eschar’ is not interchangeable with ‘scab’. An eschar contains necrotic tissue whereas a scab is composed of dried blood and  exudate .


Black eschars are most frequently attributed in medicine to cutaneous anthrax (infection by  Bacillus anthracis ), which may be contracted through herd animal exposure and also from  Pasteurella multocida  exposure in cats and rabbits. A newly identified human rickettsial infection,  R. parkeri   rickettsiosis , can be differentiated from  Rocky Mountain spotted fever  by the presence of an eschar at the site of inoculation. [ 2 ]
Eschar is sometimes called a  black wound  because the wound is covered with thick, dry, black  necrotic tissue .


Eschar may be allowed to slough off naturally, or it may require surgical removal ( debridement ) to prevent infection, especially in immunocompromised patients (e.g. if a  skin graft  is to be conducted).


If eschar is on a limb, it is important to assess peripheral pulses of the affected limb to make sure blood and lymphatic circulation is not compromised.  If circulation is compromised, an  escharotomy , or surgical incision through the eschar, may be indicated.


An  escharotic  is a substance that kills unwanted or diseased tissue, usually skin or superficial growths like warts, leaving them to  slough  off. Examples include:


Escharotics have long been used in medicine. In conventional modern practice some still are useful for topical treatment of growths such as warts. For lack of anything better in the past, escharotics once were more widely used, and for example, popular products included so-called  black salves , with ingredients such as  zinc chloride , plus sanguinarine in the form of bloodroot extract. These and others were traditional as topical treatments for localised skin cancers in  herbal medicine . They combined unreliability in eradication of the cancer, with harmful effects such as scarring, serious injury, and disfigurement. Consequently escharotic salves now are strictly regulated in most western countries, and available on prescription only. Some prosecutions have been pursued over unlicensed sales of escharotic products such as  Cansema .


Focal hyperhidrosis , also known as  primary hyperhidrosis , is a  disease  characterized by an excessive  sweating  localized in certain body regions (particularly palms, feet and underarms). Studies suggest that this condition, affecting between 1% and 3% of the US population, seems to have a genetic predisposition in about two thirds of those affected. [ 1 ]


Focal  hyperhidrosis  is sometimes referred to as  The Silent Handicap , [ 2 ]  as it has a significant impact on the quality of life, affecting the individual socially, psychologically, emotionally and professionally. [ 3 ]


In 2006, researchers uncovered that primary  palmar hyperhidrosis , referring to excess sweating on the palms of the hands and feet, maps to the gene locus 14q11.2-q13. [ 4 ]


Based on previous research using mice and rats, researchers looked towards the role of  aquaporin 5  (AQP5), a water channel protein, in human individuals with primary focal hyperhidrosis. [ 5 ]  AQP5 has been identified as a candidate gene in many hyperhidrosis studies. Using a family that had members with primary focal hyperhidrosis, researchers found that there was no connection between primary focal hyperhidrosis and AQP5. There was also no significant connection between the gene 14q11.2-q13 locus, which was linked to primary palmar hyperhidrosis, and primary focal hyperhidrosis in this family. [ 6 ]


The expression of the AQP5 protein and AQP5  mRNA  was significantly higher in a patient group in comparison to the control group. In 2011, using a control group (individuals without primary focal hyperhidrosis) and a patient group (individuals with primary focal hyperhidrosis) researchers found that there was no difference between the number of sweat coils in the axillary  sweat glands . This indicates that there is nothing  morphologically  different between individuals with and without primary focal hyperhidrosis. The discrepancies between the studies above call on further studies to confirm or deny the role of AQP5, and the role of other proteins, in hyperhidrosis. [ 7 ]


Beyond looking at the genes and individual proteins that play a role in primary focal hyperhidrosis, researchers have looked at the patterns of  heredity  for this trait. In a 2003 study, using multiple families, researchers found that primary focal hyperhidrosis was not a  sex-linked gene , since male-to-male transmission was seen in multiple families. Instead evidence supported an  autosomal dominant  pattern of inheritance with an incomplete disease  penetrance . 21 patients in this study reported a positive family history of hyperhidrosis (62%). Researchers were able to uncover this by creating  pedigrees  of all the participants in the study. Not every member of the pedigree exhibited forms of hyperhidrosis, which allowed the researchers to track the patterns of inheritance. The findings in this study indicated that primary focal hyperhidrosis is typically an hereditary disorder. [ 8 ]


Typical regions of excessive sweating include the hand palms, underarms, the sole of the foot, and sometimes groin, face, and scalp. Indeed, profuse sweating is present mostly in the underarms, followed by the feet, palms and facial region. [ 9 ]


Evidence demonstrates that a positive family history is also present (see the  Genetics  part). [ 10 ]


The Canadian Hyperhidrosis Advisory Committee has published a comprehensive set of guidelines which outlines key aspects of treatment related to this condition. Topical hyperhidrosis gels containing  aluminum chloride hexahydrate  are usually first choice treatments for this condition. [ 3 ]


In addition to topical  antiperspirants  (whose main active ingredients usually are aluminum or zirconium salts) treatment options include:  iontophoresis  (hands, feet), onabotulinumtoxinA ( Botox ) injections (underarms, hands, feet, and other localized areas), [ 11 ]  electromagnetic/ microwave energy  thermolysis  of underarm sweat glands ( miraDry ), [ 12 ]  laser-assisted removal of the sweat glands (underarms), [ 13 ]  other local procedures such as liposuction and curettage of the sweat glands (underarms), medications of the anticholinergic type that are taken by mouth, and  sympathectomy  surgery for sweating of the hands or head that can't be controlled by other means. [ 13 ]


Sofpironium bromide  is approved for the treatment of primary axillary hyperhidrosis. [ 14 ]


A number of gene mutations have been linked to conditions of or affecting the human integumentary system.


A number of  histologic stains  are used in the field of  dermatology  that aid in the diagnosis of conditions of or affecting the human  integumentary system .


There are many  human leukocyte antigen  (HLA) alleles associated with conditions of or affecting the human integumentary system


Hyposensitivity , also known as  Sensory under-responsitivity , refers to abnormally decreased  sensitivity  to sensory input.


Hyposensitivity is especially common for autistic people and is more often seen in children than adults and adolescents due to  masking . Those experiencing this have a harder time stimulating their senses than normally. They may not feel pain as easily as others, may be drawn to loud noises, be attracted to bright lights and colours, among other things. [ 1 ]


Hyposensitivity can lead to an inactivated brain. This can give concentration problems, feeling drained or feckless, depression, procrastination and also  hypersensitivities .


Auditory hyposensitivity  symptoms include:


Tactile hyposensitivity  symptoms include:


Olfactory hyposensitivity  symptoms include:


Taste hyposensitivity  symptoms include:


Visual hyposensitivity  symptoms include:


Vestibular hyposensitivity  symptoms include:


Proprioceptive hyposensitivity  symptoms include:


Several cutaneous conditions can be diagnosed with the aid of  immunofluorescence  studies.


Cutaneous conditions with positive direct or indirect immunofluorescence when using salt-split skin include:


For several subtypes of  pemphigus  a variety of substrates are used for indirect immunofluorescence:


This is a list of cutaneous  conditions associated with internal malignancy ; skin markers of internal cancer. [ 1 ]  It does not include skin infections associated with cancer or cancers that spread to skin. [ 1 ]  Some have stronger associations with cancers than others. [ 2 ]


tracts


pancreatic islet cell adenoma


Janeway lesions  are rare, non- tender , small  erythematous  or  haemorrhagic   macular ,  papular  or  nodular  lesions on the palms or  soles  only a few millimeters in diameter that are associated with  infective endocarditis  and often indistinguishable from  Osler's nodes . [ 1 ] [ 2 ]


Janeway lesions are painless, frequently haemorrhagic lesions seen most commonly on the palms and soles, particularly on the base of the thumb and little finger, and seen in infective endocarditis. [ 1 ]


Osler's nodes  and Janeway lesions are similar and point to the same diagnostic conclusion. The most significant difference between the two is that Osler's nodes present with tenderness, while Janeway lesions do not. [ 2 ]  Osler's nodes are thought to be due to immunologic phenomenon where deposition of immune complexes provoke inflammatory response, leading to swelling, redness and pain. On the contrary, Janeway lesions are thought to be due to embolic phenomenon in cutaneous blood vessels of palms and soles which does not cause pain or least pain. [ 3 ] [ 4 ]


Pathologically, the lesion is described to be a  microabscess  of the  dermis  with marked  necrosis  and inflammatory infiltrate not involving the  epidermis . [ 2 ]


They are caused by septic emboli which deposit bacteria, forming microabscesses. [ 5 ]  Organisms may be cultured from the lesions. [ 6 ]


Janeway lesions present as red, painless macules and papules on the palms and soles. [ 1 ]


They are not common and are frequently indistinguishable from  Osler's nodes . Rarely, they have been reported in cases of  systemic lupus erythematosis  (SLE),  gonococcemia  (disseminated gonorrhoea),  haemolytic anaemia  and  typhoid fever . [ 1 ]


They may last days to weeks before completely resolving. [ 1 ] [ 7 ]


Janeway lesions are named after  Edward Janeway  (1841–1911), a prominent American physician, pathologist and contemporary of Sir  William Osler , who initially described "peculiar skin lesions" in some people with endocarditis, in a paper published in 1899. The term was first used by  internist  and pathologist  Emanuel Libman , who reported the lesions in his paper of 1906 and explained his reasoning for using the term "Janeway lesions" in a footnote in 1923. Osler never mentioned Janeway lesions. The inclusion into Osler's 1925 textbook came six years after Osler died. [ 8 ]


Mutations of proteins that hold the cells of the skin together can cause disease.  Autoantibodies against proteins that hold the cells of the skin together can also cause disease.


Mucocutaneous pemphigus vulgaris [ 2 ]


Koenen's tumor  ( KT ), also commonly termed  periungual angiofibroma , [ 1 ] : 668   is a subtype of the  angiofibromas . [ 3 ]  Angiofibromas are benign papule, nodule, and/or tumor lesions that are separated into various subtypes based primarily on the characteristic locations of their lesions. KTs are angiofibromas that develop in and under the toenails and/or fingernails. [ 4 ]  KTs were once considered as the same as another subtype of the angiofibromas viz.,  acral angiofibromas . While the literature may still sometimes regard KTs as acral angiofibromas, acral angiofibromas are characteristically located in areas close to but not in the toenails and fingernails as well as in the soles of the feet and palms of the hands. [ 5 ] [ 6 ]  KTs are here regarded as distinct from acral angiofibromas.


KTs most commonly develop in individuals who have the rare  genetic disease ,  tuberous sclerosis [ 7 ]  (a heritable neurocutaneous disorder [ 8 ] ) and uncommonly in individuals that do not have this genetic disease. [ 9 ]  One individual with another rare genetic disease that has similarities to tuberous sclerosis, the  Birt-Hogg-Dube syndrome , has also been reported to have typical KT findings. [ 10 ]


KTs are strictly benign (i.e. do not  metastasize ) but may be painful, disfiguring, and sometimes large and/or incapacitating lesions. They have often been treated by strictly local surgical resections. However, they do have a high rate of recurrence at the site of resection [ 11 ]  and therefore have been treated with various other non-invasive local measures in efforts to avoid recurrences; these other methods have also been preferred to treat numerous tumors in individuals, for cosmetic reasons, and/or to relieve tumor-induce incapacitations. [ 11 ] [ 12 ]


In individuals with tuberous sclerosis, KTs commonly present with multiple firm red-colored to skin-colored nodules or tumors that emanate from the  proximal nail fold  or, less often, proximal skin beneath the nail. They often develop after puberty; increase in number over time; more frequently occur in the toenails than fingernails (the most common sites are on the big toe and thumb); are generally 5 to 10 mm in length but occasionally grow to far larger sizes; [ 4 ]  and may be or become disfiguring, painful, and/or incapacitating. [ 13 ]  Nearly 50% of post-puberty individuals with tuberous sclerosis have KTs. [ 11 ]  (Tuberous sclerosis is also associated with a second type of angiofibroma,  adenoma sebaceum , also termed facial angiofibroma, in ~75% of cases. [ 14 ] ) Individuals presenting with KTs that do not have tuberous sclerosis commonly present with a single lesion in a nail bed. [ 15 ]  KT may also present as a recurrence of a lesion at the site where it was surgically removed. [ 11 ]  Rare cases of KTs have had a history of crushing trauma at the sites where the KTs later developed. [ 4 ]


Microscopic  histopathological  analyses of KTs commonly reveal a lesion with epidermal acanthosis (i.e. thickening of the skin), hyperkeratosis (i.e. thickening of the outermost layer of the epidermis), and skin features typical of  angiofibroma  viz., spindle-shaped or star-shaped  fibroblasts  and ectatic blood vessels in a dense  collagen  fiber  connective tissue  background. [ 12 ]


In cases associated with tuberous sclerosis, KTs appear to be a result of this disease's associated genetic abnormalities, i.e.  loss-of-function mutations  in one of the two normally paired  TSC1  or one of the two normally paired  TSC2   tumor suppressor genes . As a part of their functions, the  TSC1  and  TSC2  tumor suppressor genes act to suppress the abnormal growth of cells by contributing to the suppression of the  mammalian target of rapamycin  (i.e. mTOR) protein that promotes cell growth and proliferation. Inactivation of one of the  TSC1  or  TSC2  genes appears responsible for unleashing mTor and thereby promoting the growth of the many strictly benign lesions, including KTs, that develop in individuals with tuberous sclerosis. [ 16 ]  mTOR is inhibited by  rapamycin , a drug which has been used as a topical application to successfully treat a few cases of Koenen's tumors. [ 12 ]


A small number of cases in individuals including those that do not have tuberous sclerosis may develop KTs as reactions to local traumas. [ 4 ]


The treatment of KTs has varied depending on their size, numbers, locations, symptoms, damage to tissues, and disfiguring effects. Excision may be the treatment of choice for surgically accessible lesions. [ 15 ]  However, following surgical removal, KTs have a high rate of local recurrence, [ 11 ]  particularly in cases where the lesions are not completely removed. [ 15 ]  Other treatment methods, which may be used in combination with surgical removal and/or with each other include: carbon dioxide-based  laser vaporization ;  electrocauterization ; shave excision of the tumor with phenolization (i.e. excision of the tumor’s protruding portion followed by treatment of the proximal perionych [i.e., skin around a nail] with phenol to eradicate the root of the tumor); [ 11 ]  and in individuals with tuberous sclerosis, topical application of sirolimus, i.e. rapamycin, (1% solution). [ 12 ]  Some of the latter methods have been used in order to preserve the nail matrix and  nailplate  and may be ideal for younger patients with few tumors since they may leave a normal appearing nail. [ 11 ]


A  lick granuloma , also known as  acral lick dermatitis , is a  skin disorder  found most commonly in  dogs , but also in cats. In dogs, it results typically from the dog's urge to lick the lower portion of one of their legs.


The  lesion  can initially be red, swollen, irritated, and bleeding, similar to a  hot spot  (wet eczema).  The animal's incessant licking of the lesion eventually results in a thickened, firm, oval  plaque , which is the granuloma.


A major cause of lick granuloma appears to be psychological, related to stress, anxiety,  separation anxiety , boredom, or compulsiveness.  Lick granulomas are especially seen in active dogs left alone for long periods of time.


One theory about the cause of lick granulomas is that excessive licking causes  endorphin  release, which reduces pain and makes the animal feel comfort temporarily. [ 1 ]


Other triggers include itchy skin, painful conditions caused by trauma to the skin, arthritis, neuralgia, and peripheral neuropathy. A bacterial or fungal infection of the skin can also trigger itching, as can skin mites, allergies, a reaction to an environmental irritant or toxin, hyperthyroidism, and certain types of cancer.


Treatment of the primary cause, if known, is essential.  In  psychogenic  cases, psychological factors should be identified and addressed, such as being left alone all day, being confined, and changes in the household.


Lick granuloma is a form of self-trauma and  skin disorder  in which most commonly dogs, but also cats, continuously lick a small area of their body until it becomes raw and inflamed. The most common areas affected are the lower ( distal ) portions of their legs, such as the  carpus  (wrist), [ 2 ]  or sometimes another part of their body such as the base of their tail.


Seventy percent of the time it occurs on one of the dog's left legs. [ 3 ]


The  lesion  can initially be red, shiny, swollen, hairless, irritated, and bleeding, similar to a  hot spot  (wet eczema). [ 4 ] [ 5 ]  Eventually, a raised hard plaque forms. [ 6 ]


Frequent formations of lick granulomas in the same area due to the constant licking will cause hardening, callous formation, hair loss (the hair may stop growing back), and  hyperpigmentation  to that area. [ citation needed ]


Lick granulomas sometimes become infected with  bacteria , causing  abscessed  areas or fistulous tracts ( furuncles ). [ citation needed ]


Lick granulomas are caused by a variety of factors. One common cause of lick granulomas appears to be psychological, related to stress, anxiety,  separation anxiety , [ 7 ]  boredom, or compulsiveness. [ 8 ]   Lick granulomas are especially seen in large active dogs left alone for long periods of time. [ 8 ] [ 9 ]   It is often considered to be a form of canine  obsessive-compulsive disorder . [ 10 ] [ 7 ]


Other causes include  bacterial  or  fungal  infections,  ectoparasites ,  metabolic  disease,  neoplastic  disease, trauma causing nerve damage, allergies, or joint disease.   Hot spots  may also lead to the formation of lick granulomas.


Arthritic and mobility problems in older dogs give them more time to lick and over-groom themselves. [ 11 ]


The condition becomes a vicious cycle – erosion of the skin from licking leads to pain and itching, which leads to more licking.


Treatment of the primary cause, if known, is essential.


In  psychogenic  cases, dealing with psychological factors is most important.  Factors should be identified such as being left alone all day, being confined, and changes in the household. Correction of these causes may include increased walks, avoiding confinement, and more interaction in the home.  Some veterinarians have  proposed that diet can affect  compulsive behaviors  in dogs. [ 12 ]


Drugs may be used until  behavior modification  has had time to take effect.   Antidepressants  are most commonly used, including  doxepin ,  amitriptyline ,  fluoxetine , and  clomipramine .  If the psychological factors are not corrected, the pet will usually relapse after the drugs are discontinued.   Endorphin blockers  such as  naltrexone  can be used to reduce addiction to licking, or endorphin substitutes such as  hydrocodone  may decrease the urge to lick. [ 13 ]


The animal should be tested for allergies, and treated accordingly if positive ( fatty acids ,  antihistamines , hypoallergic diet, etc.).  It may also be necessary to check  thyroid  levels, as  hypothyroidism  seems to play a role in some cases, particularly in black Labrador retrievers; thyroid medication often will resolve the problem if it is due to hypothyroidism. [ 14 ]


The lesion should also be treated.


Class 4 infrared laser treatments have been used with much success, although it may take several treatments to achieve the desired outcome.


Licking can be prevented by the use of  Elizabethan collars , dog leggings, battery-enhanced wraps, bandages, anti-licking ointments (which are bad tasting), and anti-lick strips (which are either bad tasting or simply provide a barrier).  It is important to catch lesions early and keep the animal from licking them to then reduce inflammation and development of a habit.  Topical medications  such as  corticosteroids  or  DMSO  may be effective if used early.


Small lesions may be injected with  triamcinolone  or  methylprednisolone .  Oral  antibiotics  are used to control infection.  Surgery may be performed to remove whole lesions, but there is risk of continued self-mutilation to the area afterwards.  Other potential treatments include  cryosurgery ,  laser surgery ,  radiation therapy , and  acupuncture .  It is important to note that many dogs will lick at another leg, another area on the same leg, or someplace else, creating a new lick granuloma, if they are prevented from licking at the original one while it heals.


Overall, lick granulomas are very difficult to treat, with control only being achieved in about 65 percent of cases. [ 15 ]   Some animals will continue to lick at the area despite the use of anti-lick ointments or sprays to deter them, for instance.


Many large breed dogs appear to be predisposed, as well as  golden retrievers [ 16 ]  and other  bird dogs . [ 8 ]  Most of the dogs with the condition are over five years of age. [ 7 ]


[ 17 ]
 [ 13 ]
 [ 18 ]
 [ 19 ]


Microvascular occlusion  refers to conditions that can present with  retiform purpura . [ 1 ]  It has been suggested that  phenylephrine  may be a cause. [ 2 ]


Microvascular occlusions appears as bland  necrosis  without inflammation and  retiform purpura . [ 3 ]


Microvascular occlusions can be caused by  heparin-induced thrombocytopenia ,  cryoglobulinemia , angioinvasive organisms,  embolization ,  disseminated intravascular coagulation ,  livedoid vasculopathy , cell occlusion syndromes, and  iatrogenic  causes. [ 3 ]


The outcomes of microvascular occlusions are usually influenced by the degree, length, nature of the underlying cause, and prompt and effective treatment. [ 3 ]


A number of cutaneous conditions can occur on the skin and appear to move or migrate through the skin. [ 1 ]


Morgellons  ( / m ɔːr ˈ ɡ ɛ l ə n z / ) is the informal name of a self-diagnosed, scientifically unsubstantiated  skin condition  in which individuals have sores that they believe contain fibrous material. [ 1 ] [ 2 ]  Morgellons is not well understood, but the general medical consensus is that it is a form of  delusional parasitosis , [ 3 ]  on the psychiatric spectrum. [ 4 ]  The sores are typically the result of compulsive scratching, and the fibers, when analysed, are consistently found to have originated from cotton and other textiles. [ 2 ] [ 5 ]


The  condition was named  in 2002 by Mary Leitao, [ 6 ]  a mother who rejected the  medical diagnosis  of her son's delusional parasitosis. She chose the name from a letter written by a mid-17th-century physician. [ 7 ] [ 8 ]  Leitao and others involved in her Morgellons Research Foundation successfully lobbied members of the  U.S. Congress  and the U.S.  Centers for Disease Control and Prevention  (CDC) to investigate the condition in 2006. [ 9 ] [ 10 ]  CDC researchers issued the results of their multi-year study in January 2012, indicating that no disease  organisms  were present in the samples from the individuals examined and that the fibers found were likely cotton. The researchers concluded that the condition was "similar to more commonly recognized conditions such as delusional infestation". [ 11 ] [ 12 ]


Morgellons is poorly understood but the general medical consensus is that it is a form of  delusional parasitosis  in which individuals have some form of  skin condition  with sores that they believe contain fibers. [ 1 ] [ 2 ] [ 5 ] [ 13 ]  Its presentation is very similar to delusional parasitosis, with the addition that people with the condition believe there are inanimate objects in their skin lesions. An active online community supports the notion that it is an infectious disease, disputes that it is psychological, and proposes an association with  Lyme disease .  Controversy has resulted; publications "largely from a single group of investigators" describe findings of  spirochetes ,  keratin  and  collagen  in skin samples in small numbers of patients; these findings are contradicted by much larger studies conducted by the CDC, which found skin samples mostly contained  cellulose  that came from cotton, with no evidence of infection or other causes. [ 5 ]


In 2001, [ 6 ]  according to Leitao, her then-two-year-old son developed sores under his lip and began to complain of bugs. [ 14 ]  Leitao says she examined the sores with her son's toy microscope and discovered red, blue, black, and white fibers. [ 6 ] [ 7 ]  She states that she took her son to see at least eight different doctors who were unable to find any disease, allergy, or anything unusual about her son's described symptoms. Fred Heldrich, a  Johns Hopkins  pediatrician with a reputation "for solving mystery cases", examined Leitao's son. [ 6 ]  Heldrich found nothing abnormal about the boy's skin, and wrote to the referring physician that "Leitao would benefit from a psychiatric evaluation and support", and registered his worry about Leitao's "use" of her son. [ 6 ]  Leitao last consulted an unnamed Johns Hopkins  infectious disease specialist  who refused to see her son after reviewing his records, and suggested Leitao herself might have " Munchausen's by proxy , a psychiatric syndrome in which a parent pretends a child is sick or makes him sick to get attention from the medical system". [ 7 ]  According to Leitao, several medical professionals she sought out shared this opinion of a potential psychological disorder: [ 15 ]


[Leitao] said she long ago grew accustomed to being doubted by doctors whenever she sought help for her son, who is now seven and still suffering from recurring lesions. "They suggested that maybe I was neurotic," Leitao said. "They said they were not interested in seeing him because I had Munchausen Syndrome by Proxy." [ 16 ]


Leitao says that her son developed more sores, and more fibers continued to poke out of them. [ 7 ] [ 14 ]  She and her husband, Edward Leitao, an  internist , felt their son had "something unknown". [ 6 ]


Leitao chose the name  Morgellons disease  (with a hard  g ) from a description of an illness in the medical case-history essay,  A Letter to a Friend  (c. 1656, pub. 1690) by Sir  Thomas Browne , where the physician describes several medical conditions in his experience, including "that endemial distemper of children in  Languedoc , called the  morgellons , wherein they critically break out with harsh hairs on their backs". [ 7 ] [ 8 ]


Leitao started the Morgellons Research Foundation (MRF) informally in 2002 and as an official non-profit in 2004. [ 7 ] [ 17 ]  The MRF website states that its purpose is to raise awareness and funding for research into the proposed condition, described by the organization as a "poorly understood illness, which can be disfiguring and disabling". [ 18 ]  Leitao stated that she initially hoped to receive information from scientists or physicians who might understand the problem, but instead, thousands of others contacted her describing their sores and fibers, as well as neurological symptoms, fatigue, muscle and joint pain, and other symptoms. [ 7 ]   The MRF claimed to have received self-identified reports of Morgellons from all 50  U.S. states  and 15 other countries, including Canada, the UK, Australia, and the Netherlands. It also claimed that it had been contacted by over 12,000 families. [ 18 ]


In 2012, the Morgellons Research Foundation closed down and directed future inquiries to the  Oklahoma State University . [ 19 ]


In May 2006, a CBS news segment on Morgellons aired in Southern California. [ 20 ]  The same day, the Los Angeles County Department of Health services issued a statement saying, "No credible medical or public health association has verified the existence or diagnosis of 'Morgellons Disease ' ", and "at this time there is no reason for individuals to panic over unsubstantiated reports of this disease". [ 21 ]  In June and July 2006, there were segments on  CNN , [ 22 ]   ABC 's  Good Morning America , [ 23 ]  and  NBC 's  The Today Show . In August 2006, a segment of the ABC show  Medical Mysteries [ 14 ]  was devoted to the subject. Morgellons was featured on  ABC 's  Nightline  on January 16, 2008, [ 24 ]  and as the cover story of the January 20, 2008, issue of  The Washington Post . [ 9 ]


The first article to propose Morgellons as a new disease in a scientific journal was a review article co-authored by members of the MRF and published in 2006 by the  American Journal of Clinical Dermatology . [ 25 ]  A 2006 article in the  San Francisco Chronicle  reported, "There have been no clinical studies" of Morgellons disease. [ 25 ]  A  New Scientist  article in 2007 also covered the phenomenon, noting that people are reporting similar symptoms in Europe and Australia. [ 26 ]


In an article published in the  Los Angeles Times  on April 22, 2010, singer-songwriter  Joni Mitchell  claimed to have the condition. [ 27 ]


On June 13, 2011, the  Australian Broadcasting Corporation 's  Radio National  broadcast  The Mystery of Morgellons  with guests including  Mayo Clinic  Professor Mark Davis. [ 28 ]


The Morgellons Research Foundation coordinated a mailing campaign via their website, in which thousands of people sent  form letters  to a  Centers for Disease Control and Prevention  (CDC) task force, which first met in June 2006. [ 9 ] [ 29 ] [ 30 ]  By August 2006, the task force consisted of 12 people, including two pathologists, a toxicologist, an ethicist, a mental health expert, and specialists in infectious, parasitic, environmental and chronic diseases. [ 31 ]


In June 2007, the CDC started a website relating to Morgellons,  CDC Study of an Unexplained Dermopathy , and by November 2007, the CDC opened an investigation into the condition. [ 10 ]   Kaiser Permanente , a health-care consortium in Northern California, was chosen to assist with the investigation, which involved skin biopsies from affected people and characterization of foreign material such as fibers or threads obtained from people to determine their potential source. [ 10 ] [ 32 ]  The U.S. Armed Forces Institute of Pathology and the  American Academy of Dermatology  assisted with pathology. [ 33 ]  In January 2012, the CDC released the results of the study. [ 11 ] [ 12 ]


The CDC concluded that 59% of subjects showed  cognitive deficits  and 63% had evidence of clinically significant symptoms. They stated that 50% of the individuals had drugs in their systems, and 78% reported exposure to  solvents  (potential skin irritants). The study detected no parasites or  mycobacteria  in the samples collected from any individuals. Most materials collected from participants' skin were composed of  cellulose , likely of cotton origin. [ 11 ]


An active online community and publications "largely from a single group of investigators" have supported the notion that Morgellons is an infectious disease, and propose an association with  Lyme disease ; these findings are contradicted by the much larger studies conducted by the CDC. [ 5 ]  People usually self-diagnose Morgellons based on information from the internet and find support and confirmation in online communities of people with similar illness beliefs. [ 34 ] [ 35 ] [ 36 ]  In 2006, Waddell and Burke reported the influence of the internet on people self-diagnosed with Morgellons: "physicians are becoming more and more challenged by the many persons who attempt self-diagnosis on-line. In many cases, these attempts are well-intentioned, yet wrong, and a person's belief in some of these oftentimes unscientific sites online may preclude their trust in the evidence-based approaches and treatment recommendations of their physician." [ 37 ]


Physician Fidel Vila-Rodriguez wrote in a 2008 editorial that the Internet promotes the spreading and supporting of "bizarre" disease beliefs because in online communities, "a belief is not considered delusional if it is accepted by other members of an individual's culture or subculture". [ 35 ]   Robert Bartholomew , a sociologist who has studied the Morgellons phenomenon, states that the "World Wide Web has become the incubator for mass delusion and it (Morgellons) seems to be a socially transmitted disease over the Internet." According to this hypothesis, people with delusions of parasitosis and other psychological disorders become convinced they have "Morgellons" after reading internet accounts of others with similar symptoms. This phenomenon is known as  mass psychogenic illness , where physical symptoms without an organic cause spread to multiple people within the same community or social group. [ 38 ]  The  Dallas Observer  writes that Morgellons may be  memetically  spread via the internet and mass media, and "[i]f this is the case, then Morgellons is one in a long line of weird diseases that have swept through populations, only to disappear without a trace once public concern subsides". [ 17 ]  The article draws parallels to several media-spread  mass delusions .


Dermatologist Caroline Koblenzer specifically faults the Morgellons Research Foundation (MRF) website for misleading people: "Clearly, as more and more of our patients discover this site (MRF), there will be an ever greater waste of valuable time and resources on fruitless research into fibers, fluffs, irrelevant bacteria, and innocuous worms and insects." [ 39 ]  A 2005  Popular Mechanics  article stated that Morgellons symptoms are well known and characterized in the context of other disorders, and that "widespread reports of the strange fibers date back" only a few years to when the MRF first described them on the Internet. [ 40 ]  The  Los Angeles Times , in an article on Morgellons, notes that "[t]he recent upsurge in symptoms can be traced directly to the Internet, following the naming of the disease by Mary Leitao, a Pennsylvania mother". [ 36 ]


In 2008,  The Washington Post  reported that internet discussions about Morgellons include many  conspiracy theories  about the cause, including  biological warfare ,  nanotechnology ,  chemtrails  and  extraterrestrial life . [ 9 ]   The Atlantic  says it "even received pop-culture attention" when it was featured on  Criminal Minds , adding that "Morgellons patients have further alienated themselves from the mainstream medical community" by "linking Morgellons to another illness viewed skeptically by most doctors,  chronic Lyme disease , and by attacking those who doubt their condition". [ 41 ]


Mosquito bite allergies , also termed  hypersensitivity to mosquito bites , are excessive reactions of varying severity to  mosquito bites . They are  allergic   hypersensitivity reactions  caused by the non-toxic  allergenic  proteins contained in the  saliva  injected by a female mosquito (male mosquitos do not take blood-meals) at the time it takes its blood meal, and are not caused by any  toxin  or  pathogen .  By general agreement, mosquito bite allergies do not include the ordinary  wheal  and flare responses to these bites although these reactions are also allergic in nature. [ 1 ]  Ordinary mosquito bite allergies are nonetheless detailed here because they are the best understood reactions to mosquito bites and provide a basis for describing what is understood about them.


Mosquito bite allergies are informally classified as  1)  the  skeeter syndrome , i.e., severe local skin reactions sometimes associated with low-grade fever;  2)   systemic reactions  that range from high-grade fever,  lymphadenopathy , abdominal pain, and/or diarrhea to, very rarely, life-threatening symptoms of  anaphylaxis ; and  3)  severe and often systemic reactions occurring in individuals that have an  Epstein-Barr virus-associated lymphoproliferative disease , Epstein-Barr virus-negative  lymphoid malignancy , [ 2 ]  or another predisposing condition such as  eosinophilic cellulitis  or  chronic lymphocytic leukemia . [ 3 ]  The term papular urticaria [ 4 ]  is commonly used for a reaction to mosquito bites that is dominated by widely spread  hives . Here, papular urticaria is regarded as a symptom of mosquito bite allergy manifested in individuals with one of the other mosquito bite allergies but particularly in those associated with eosinophilic cellulitis.


Mosquitos belong to the biological  order  of  Diptera  (which includes all two-winged insects), suborder  Nematocera , family Culicidea. [ 5 ]  There are >3,500 different mosquito species with the  Aedes  and  Culex  genera being common in North America. It is assumed that any species of mosquito that causes an ordinary mosquito bite reaction in humans is capable of causing mosquito bite allergies. [ 6 ]   In addition to mosquitoes, the Diptera order includes numerous other types of biting insects such as  midges  (e.g.  sand flies ) and  gnats . Bites by the latter insects [ 1 ]  or possibly some other insects [ 7 ]  may cause reactions that are mechanistically and clinically similar to those seen with mosquito bites. [ 1 ]


Mosquito bite allergies occur more often where insect bites are frequent. Consequently, cases (as well as various other allergic disorders) are more prevalent in tropical climates, underdeveloped areas, areas dominated by poverty, poor hygiene, and/or unawareness of these diseases, and urban areas plagued by social inequality, juvenile delinquency, and violence. That is, not only climate but also cultural and socioeconomic conditions play critical roles in facilitating the development and prevalence of diverse allergic disease including mosquito bite allergies. [ 7 ]


The typical reaction to mosquito bites involves the development of an itchy  wheal  that may contain a central red dot and is surrounded by splotchy redness. This "immediate reaction" occurs at some time during the first 20 minutes following the bite. Within hours of the bite, a "delayed reaction", in which the wheal evolves into a  papule  develops and then dissipates over the next few days or weeks. [ 1 ]  However, there is a wide variability in the type of reaction which individuals mount in response to these bites. The initial mosquito bites in previously unexposed individuals does not cause a skin reaction but does initiate the development of  antibodies  and/or lymphocytes that are directed against the  allergens  in mosquito's saliva. These individuals thereby become sensitized and reactive to subsequent mosquito bites. After repetitive mosquito bites, individuals may become less sensitive or completely insensitive to the bites in the natural process of  allergen desensitization . Individuals therefore progress through 5 stages in which the type of reaction to a mosquito bite depends on the number of their previous bite exposures and levels of acquired sensitization and desensitization to these bites. The 5 stages an individual may undergo in reacting to repetitive mosquito bites are: [ 6 ]


In a study of 41 Canadian adults experimentally exposed to mosquito bites, 11 individuals exhibited no reaction, 23 individuals exhibited immediate followed by delayed reactions, 6 individuals exhibited only immediate reactions, and 1 individual exhibited only a delayed reaction. [ 3 ]  Overall, 70-90% of individuals experience an immediate reaction and 55-65% experience a delayed reaction to mosquito bites. [ 6 ]


Individuals also vary in the severity of their reactions to mosquito bites. Most individuals show a "small reaction" in which a 2–10 mm (0.1-0.4 inches) diameter wheal evolves into a similarly sized papule that dissipates over several days. [ 6 ]  About 2.5% of individuals (based on self reports) [ 6 ]  show a "large reaction" in which the wheal is much larger than 10 mm (it may exceed 3 cm, i.e. 1.2 inches) in diameter and evolves into an extensive lesion that has black and blue discolorations due to subcutaneous bleeding,  blistering , and/or  necrosis . The latter reactions, which appear to be caused by the development of an inflammatory  Arthus reaction  at the site, may be very painful. [ 1 ]


Mosquito saliva contains >30 potentially allergenic proteins. More than 11 of these have been identified in the saliva of the  Aedes egypti  mosquito. Four such proteins, termed Aed a 1 (an apyrase), Aed 2 (Female-specific protein, D7), Aed 3 (an as yet undefined protein), and Aed a 4 (an α-glucosidase) have been purified as  recombinant proteins . Each of these recombinants causes immediate and delayed skin reactions when injected into volunteers with a history of mosquito bite reactivity. As exemplified by the Aed proteins, the proteins in the saliva of any biting mosquito are thought to cause individuals who have not been previously bitten to:  a)   make IgE and IgG antibodies that bind the proteins inducing their formation and  b)  develop  T cells  (a type of  lymphocyte ) that react against parts of the inducing proteins that are displayed on the surface of cells at the bite site (see  Antigen presentation ). In subsequent mosquito bites, IgE and IgG appear involved in the development of both immediate and delayed skin reactions while T cells appear involved in development of the delayed skin reactions. [ 8 ]  The acquired IgE binds mosquito saliva proteins and then triggers skin tissue cells such as  mast cells  to release at least two mediators of allergic reactions,  histamine  and  leukotriene C4 . These mediators contribute to the development of the wheal, itch, and other components of the immediate reaction. This part of the immediate reaction is a classical  type I hypersensitivity reaction . The acquired IgG binds mosquito saliva proteins to form an  immune complex -triggered   type III hypersensitivity reaction  that recruits blood  leukocytes , including T cells, into the bite area; this response it thought to be required for developing the early stage of the delayed reaction. T cells present in or recruited to the mosquito bite area appear responsible for mediating the full delayed reaction. The full delayed reaction is a  type IV hypersensitivity reaction . [ 6 ]


The diagnosis of ordinary mosquito reactions is made on the basis of the history and clinical features of mosquito bites. [ 6 ]


Reducing mosquito breeding areas (e.g. eliminating standing water pools, stocking ponds with fish that consume mosquito larva) and the use of other  mosquito control  methods such as insecticides, mosquito traps, protective clothing, bed nets, and repellants (e.g.  DEET  or  permethrin ) are effective, highly recommended means for reducing mosquito bites. [ 6 ]  Daily doses of a non-sedating second-generation  anti-histamines  (e.g.  cetirizine  or  levocetirizine ) can effectively reduce the immediate and delayed reactions to mosquito bites. [ 8 ]  The use of recombinant mosquito saliva proteins to  desensitize  individuals against developing reactions to mosquito bites has yielded variable results and requires further study. [ 6 ]


Treatment of ordinary small or large mosquito bite reactions is limited to the use of non-sedative  H1 antihistamines , e.g.  cetirizine [ 6 ]
or a drug with combined activity in inhibiting histamine and  platelet-activating factor , e.g.  rupatadine . [ 9 ]  Randomized, double-blinded, placebo-controlled studies are needed to determine if  antileukotriene  drugs or  topical steroids  have beneficial effects in reducing the symptoms of these bites. [ 6 ]


The Skeeter syndrome is by definition a mosquito bite allergy that consists of a large mosquito bite reaction that may be accompanied by a brief or longer-term (i.e. days to weeks) low-grade fever. [ 8 ]  and, on rare occasions, vomiting. [ 10 ]  The bite site shows an intense, large reaction often resembling a  cellulitis  infection that persists for days to weeks. [ 5 ]  The syndrome usually afflicts healthy children, immune-deficient persons, and individuals who are new to an area inhabited by mosquito species to which they have not been exposed. [ 6 ]


Mechanistically, the Skeeter syndrome appears to be a particularly intense variant of the ordinary mosquito bite reaction. It involves sequential Type I, III, and IV hypersensitivity reactions [ 6 ]  that are mediated by the IgE, IgG, and T cells that are directed against mosquito salivary proteins. [ 1 ]


Children afflicted with the syndrome remain healthy although subject to recurrent severe reactions to mosquito bites. The development of desensitization that follows repetitive mosquito bites and reduces the intensity or completely blocks reactions to mosquito bites may take longer to develop and/or be less effective in those with Skeeter syndrome compared to those with ordinary mosquito bite reactions. [ 11 ]


The diagnosis of Skeeter syndrome is based mainly on the appropriate history of severe skin responses to mosquito bites that may be associated with fever. The diagnosis can be supported by the detection, using for example an  ELISA assay ),  IgE  directed against mosquito saliva proteins in the afflicted individuals serum. [ 8 ]  Direct mosquito bite testing is perhaps the best method for diagnosing mosquito bite allergy but difficulty in determining which mosquito species to use for the test, the possibility of transmitting a mosquito-borne disease, and the risk of triggering a very severe response make this test impractical for routine use. [ 6 ]


The preventive measures listed for ordinary mosquito bite reactions are important for avoiding Skeeter syndrome reactions. In addition to second generation, non-sedative H1 antihistamines,  antipyretics  and  nonsteroidal anti-inflammatory drugs  are typically used to treat patients with acute attacks of the syndrome. [ 6 ]


Individuals with systemic mosquito bite allergies respond to mosquito bites with intense local skin reactions (e.g. blisters, ulcers, necrosis, scarring) and concurrent or subsequent systemic symptoms (high-grade fever and/or  malaise ; less commonly,  muscle cramps , bloody diarrhea, bloody urine,  proteinuria , and/or  wheezing ; [ 3 ]  or very rarely, symptoms of overt anaphylaxis such as  hives ,  angioedema  (i.e. skin swelling in non-mosquito bite areas), shortness of breath, rapid heart rate, and low blood-pressure). [ 8 ]  There are very rare reports of death due to anaphylaxis following mosquito bites. [ 6 ]  Individual with an increased risk of developing severe mosquito bite reactions include those experiencing a particularly large number of mosquito bites, those with no previous exposure to the species of mosquito causing the bites, and those with a not fully developed immune system such as infants and young children. [ 8 ]  Individuals with certain  Epstein-Barr virus-associated lymphoproliferative , [ 12 ]  non-Epstein-Barr virus malignant lymphoid, [ 2 ]  or other predisposing disease [ 3 ]  also have an increased rate of systemic mosquito bite reactions but are considered in a separate category .


Systemic mosquito bite reactions appear to be primarily Type I hypersensitivity reactions that are critically mediated by IgE directed against mosquito salivary gland proteins. [ 8 ]


The methods used to diagnose systemic mosquito bite allergies are similar to those used to diagnose the Skeeter syndrome, including typical case history and, in particular, ELISA tests to detect specific IgE directed against mosquito salivary proteins. [ 8 ]


The methods used to avoid  mosquito  bites  are of particularly importance for preventing systemic mosquito bite allergies, given their severity. These include avoiding mosquito-infested areas, the use of repellants such as  DEET  or  permethrin , and mosquito bite desensitization procedures once they have been shown to be safe and effective for this severest form of mosquito allergy. [ 8 ]


Systemic mosquito bite reactions are serious and on rare occasions may be life-threatening. [ 6 ]  Individuals at risk for developing anaphylactic symptoms in response to mosquito bites should carry an  Epinephrine autoinjector  for immediate use following a mosquito bite. These individuals as well as those without self-injecting epinephrine who develop symptoms of  anaphylaxis  following a mosquito bite should be treated as medical emergencies requiring  anaphylaxis management . [ 8 ]  Individuals with less severe symptoms of systemic mosquito bite reactions require monitoring and treatments tailored to their symptoms. These treatments may include systemic corticosteroids, second generation H1 anti-histamines, and anti-pyretics similar to those used to treat the Skeeter syndrome. [ 6 ]


Mosquito bite allergies afflict individuals who have any one of various types of  Epstein–Barr virus-associated lymphoproliferative diseases  (EBV+ LPD). [ 13 ]  About 33% of patients with  chronic active EBV infection  are afflicted by mosquito bite allergies. Other Epstein-Barr virus-associated lymphoproliferative disease reported to predispose individuals to mosquito bite allergies include Epstein-Barr virus-positive  Hodgkin disease , [ 14 ]   hydroa vacciniforme , [ 15 ]   hemophagocytic lymphohistiocytosis , [ 16 ]   aggressive NK-cell leukemia  (also termed aggressive NK-cell leukemia/lymphoma), [ 14 ]  and  extranodal NK/T-cell lymphoma, nasal type . [ 13 ]  Mosquito bite allergies in individuals with chronic active Epstein-Barr virus infection is the best studied of those that occur in Epstein-Barr virus-associated lymphoproliferative disease; much of what is known in this area is based on these individuals. [ 13 ]


Cases of mosquito bite allergies associated with Epstein-Barr virus-associated lymphoproliferative disease have been reported most often in Japan, Taiwan, Korea, and the native populations of Mexico, Central America, and South America. [ 14 ]  This reaction occurs primarily in younger individuals (0–18 years old; mean age 6.7 years) who have evidence of one of the predisposing Epstein-Barr virus-associated lymphoproliferative disease. [ 3 ]  Rarely, however, it occurs in individuals who exhibit no signs or symptoms of a predisposing disorder but later develop chronic active Epstein-Barr virus infection. [ 3 ] [ 17 ]  In addition to the signs and symptoms of their specific Epstein-Barr virus-associated lymphoproliferative disease (see  Epstein-Barr virus-associated lymphoproliferative diseases ), these individuals are subject to severe local as well as systemic reactions to mosquito bites. [ 3 ]  The bite sites are infiltrated with  T helper cells ,  CD8+ T cells , and  CD16 +  NK cells . In this mixture of infiltrates, most of the cells exhibiting EBV positivity are  T helper cells . [ 13 ]  The systemic reactions include: fever and  malaise ; [ 12 ]  enlarged lymph nodes, liver, and/or spleen; liver dysfunction; hematuria; and proteinuria. [ 1 ]  The individuals exhibit greatly increased numbers off circulating NK cells, increased levels of T helper cells. and increased levels of  IgE . [ 13 ]  Some of the circulating NK cells are clearly infected with EBV. The mosquito bitten tissues show perivascular infiltrations containing  T  and NK cells; a large percentage of these NK cells are EBV positive. [ 14 ]  Cases associated with chronic active Epstein-Barr virus infection commonly progress to a more serious Epstein-Barr virus-associated lymphoproliferative disease such as  marginal zone B-cell lymphoma  or a Hodgkin lymphoma-like B cell lymphoma. [ 14 ]


The allergenic proteins in the mosquito's salivary are thought to trigger the reactivation of EBV in the NK cells that are  latently infected  with the virus. Upon reactivation, the virus expresses certain of its gene products, particularly that of its  LMP1   oncogene , [ 13 ]  as well as induces its infected cells to release certain of their gene products, particularly  interferon gamma  and  interleukin 10 , [ 3 ]  which cause the cells it infects to lyse and release EBV to infect other cells or, alternatively, to become immortalized, proliferate, and, possibly, become malignant. [ 13 ]


The diagnosis of mosquito bite allergies in Epstein-Barr virus-associated lymphoproliferative disease depends on finding evidence of the lymphoproliferative disease, a compatible clinical presentation, and detection of EBV in the NK and T cells (e.g. T helper cells) in blood and/or mosquito bitten tissues. The presence of high levels of EBV+ circulating NK cells strongly supports the diagnosis. However, an exceptionally high density of EBV+ in the skin lesions and/or blood raises the possibility that the individual has a NK-cell lymphoma/leukemia. [ 6 ]  Lympoid cells at the bite site may also express the EBV1 viral gene,  BZLF1 ; this gene promotes the lyses of its infected cell host and when detected in bite sites is a marker of a poor prognosis. [ 13 ]


The best treatment for mosquito bite allergy in individuals with an Epstein-Barr virus-associated lymphoproliferative disease varies. Mild and clearly uncomplicated cases with, for example, indolent CAEV, are treated conservatively focusing on obtaining relief of symptoms such as skin irritation, fever, and malaise. [ 17 ]  Cases with evidence of significant complications of CAEFV such as the development of hemophagocytosis, NK/T cell lymphoma, or aggressive NK cell lymphoma generally require chemotherapeutic regimens directed at these complications. Individuals with EBV+ systemic mosquito bite allergy and clear evidence of concurrent aggressive chronic active Epstein-Barr virus infection have been treated with relative success by the 3 step regimen used to treat the latter. [ 2 ]  Rare cases of systemic mosquito bite allergy have been reported to occur in individuals who have no apparent predisposing disease but later develop chronic active Epstein-Barr virus infection. [ 14 ] [ 17 ]  Such cases require careful evaluation and follow-up for development of a predisposing disorder. [ 17 ]


Eosinophilic cellulitis , also known as Wells syndrome, is a rare  skin disease  usually occurring on the extremities and/or trunk that is characterized by episodic acute  urticarial  eruptions or  erysipelas -like rashes which proceed to develop over the ensuing ~6 weeks into  granuloma -like or  morphea -like lesions. The initial lesions may be  papules ,  plaques ,  vesicles , or  blisters  and give a burning or itchy sensation. [ 18 ]  The eruptions may be accompanied by fever,  arthralgia  or other systemic symptoms. [ 19 ]  The disorder predominantly affects adults, frequently takes a protracted course, and has a high rate of spontaneous remission but is often recurrent with relapses occurring even long after remissions. One study found a relapse rate of 56% during an observation period of up to 19 months. Relapses are more frequent in adults than in children. While these lesions usually resolve without sequelae, they may result in skin atrophy and hyperpigmentation. [ 18 ]  Individuals afflicted with eosinophilic cellulitis may have a history of other diseases including  various eosinophlic skin diseases ,  abnormally high levels of circulating blood eosinophils , the  hypereosinophilic syndrome ,  eosinophilic granulomatosis with polyangiitis ,  ulcerative colitis ,  arthralgias ,  myalgias ,  facial nerve paralysis ,  photosensitivity , [ 18 ]   polycythemia vera ,  chronic myeloid leukemia , [ 20 ]   chronic lymphocytic leukemia ,  Hodgkin lymphoma ,  nasopharyngeal cancer , and  renal cell carcinoma . [ 18 ]  Episodes of the disorder are sometimes triggered by: drugs (e.g. antimicrobial agents, biologics, antihypertensive agents,  diuretics , thyroid hormones,  analgesics ,  cytostatic agents , and  anesthetics );  vaccines ; skin contact with chemicals (e.g.  p-phenylenediamine ,  thiomersal , [ 18 ]  and  cladribine ); viral, bacterial, fungal, and parasitic infections; and insect bites. [ 18 ]


Mosquitoes trigger mosquito bite allergies in individuals with eosinophilic cellulitis, They are also thought to trigger mosquito bite allergies that are followed by and therefore trigger the development of eosinophilic cellulitis in individuals with no prior evidence of the disease. It is also possible, however, that these individuals have an undiagnosed, latent form of the disease. The acute eruptions, which may be singular or multiple, occur at the bite site and may spread locally or to more  distant skin sites. The classification of all these eosinophilic cellulitis reactions, whether triggered by a mosquito bite, triggered by some other agent, or apparently untriggered, is argued; [ 3 ]  it has been proposed that eosinophilic cellulites is not a distinct clinical entity but rather a set of skin reactions in various diagnosed or yet-to be diagnosed disorders that involve hypereosinophilia, dysfunctional eosinophils, and/or pathological reactions to foreign antigens which predispose individuals to developing these reactions. [ 19 ]  Eosinophilic cellulitis-associated mosquito bite allergies appear to be non-specific  type IV hypersensitivity reactions  in which  T helper cells  release  cytokines  such as IL5 to attract, activate, promote the degranulation, and prolong the survival of eosinophils. These eosinophils discharge  eosinophilic cationic ,  major basic , and other proteins which injure cells and tissues and thereby may contribute to the severity of the skin lesions. [ 18 ]  The lesions typically are scattered red nodules or diffuse areas consisting of eosinophil infiltrates and flame-like figures composed of eosinophil deposits and  collagen  bundles. Over time, these lesions become  granulomatous  and scarred. Patients with the disorder may have numerous scars due to previous bouts of mosquito bite allergies. [ 18 ]


The diagnosis, which may be difficult to distinguish from other skin disorders, is based on a history of mosquito bites and previous or concurrent predisposing diseases, the course taken by the skin lesions, and the pathology of these lesions. Blood eosinophil levels are elevated in about half of these cases. [ 19 ]  The disorder has generally been either untreated or treated with short- or longer-term oral  glucocorticoids ,  topical glucorocoricoids , and/or injections of glucocorticoids into the skin lesions, depending or lesion severity. Oral antihistamines are used to alleviate associated itchiness.  Anti-inflammatory  drugs and  immunomodulatory agents  such as  dapsone ,  hydroxychloroquine ,  cyclosporine ,  interferon alfa ,  tacrolimus ,  TNF inhibitors , various antifungal agents, and numerous other agents [ 18 ]  have been used to treat the disorder in  case reports  but their value in treating the disorder as well as mosquito bite allergies is unclear. [ 18 ]  If a causative disorder triggering or predisposing to the development of eosinophilic cellulitis is identified, the best treatment option is to treat this disorder. [ 18 ]  Patients with eosinophilic cellulitis should be followed to determine if their disorder progresses into a more serious disease such as the  hypereosinophilic syndrome ,  eosinophilic fasciitis , or the  eosinophilic granulomatosis with polyangiitis . [ 20 ]


Several case reports have found individuals with chronic lymphocytic leukemia are predisposed to develop severe skin reactions to mosquito and other insect bites. However, there are reports that chronic lymphocytic leukemia patients can develop similarly severe skin reactions in the absence of an insect bite history. The pathology of the insect bite sites in these cases resembles the findings in lesions of eosinophilic cellulitis in individuals with mosquito bite allergies but the mechanism behind these reactions is unknown. [ 3 ]  There are too few reports to establish treatment recommendations for mosquito bite allergy I chronic lymphocytic leukemia beyond those generally used to treat other types of mosquito bite allergies. [ 3 ] [ 13 ]


In rare cases,  mantle cell lymphoma , a subtype of  B-cell lymphomas , has been reported in association with mosquito bite allergies. In several of these cases, the mosquito bite allergies occurred before the diagnosis of mantle cell lymphoma, suggesting that mosquito bite allergies can be a manifestation of early development, and therefore a harbinger of mantle cell lymphoma. While most of these cases have not been associated with EBV infection, some cases of mosquito bite allergies in Asia have been reported to occur in EBV-positive MBL. Because of the rarity of these cases, the difference between EBV-negative and EBV-positive mantle cell lymphoma as well as the best treatments for mosquito bite allergies in these two forms of mantle cell lymphoma have not been determined. [ 3 ] [ 13 ]


There are many different  keratin  proteins normally expressed in the human integumentary system.  Mutations in keratin proteins in the skin can cause disease.


Of note, other structural proteins in the epidermis of the skin that are closely related to keratins may also cause disease if mutated.  Examples include:


Neonatal pustular eruptions  are a group of disorders characterized by various forms of  pustulosis  (rashes consisting at least in part of pustules) seen in the first four weeks of life. [ 1 ]


This grouping can help aid in  differential diagnosis .


Neonatal pustular eruptions can be further divided into  noninfectious  and  infectious  causes, and range from benign to life-threatening. [ 2 ]  In at least some populations, the infectious causes are more common. [ 3 ]


The non-infectious causes are generally benign and self-limited. [ 4 ]


Most commonly these are primary cutaneous infections, caused by  Staphylococcus aureus  or  beta-hemolytic streptococci . This would be called bullous impetigo. When more severe, these cutaneous infections would develop into furuncles (infections run deeper into the skin).


Congenital syphilis  is another bacterial infection of the skin that can cause pustules in the neonatal period.


Listeriosis


Nevus comedonicus , also known as a  comedo nevus [ 1 ]  is characterized by closely arranged, grouped, often linear, slightly elevated  papules  that have at their center keratinous plugs resembling  comedones . [ 2 ] : 634  [ 3 ] : 774


This Epidermal nevi, neoplasms, cysts article is a  stub . You can help Wikipedia by  expanding it .


A  non-blanching rash  ( NBR ) is a skin  rash  that does not  fade  when pressed with, and viewed through, a  glass .


It is a characteristic of both  purpuric  and  petechial  rashes. [ 1 ]  Individual purpura measure 3–10 mm (0.3–1 cm,  3 ⁄ 32 - 3 ⁄ 8  in), whereas  petechiae  measure less than 3 mm. [ 2 ]


A non-blanching rash can be a symptom of  bacterial meningitis , [ 3 ]  but this is not the exclusive cause. [ 1 ] [ 4 ]


There are several conditions of or affecting the human integumentary system that are associated with an increased risk of developing nonmelanoma skin cancer (i.e.  squamous-cell carcinoma  and  basal-cell carcinoma ).


Nonthrombocytopenic purpura  is a type of  purpura  (red or purple skin discoloration) not associated with  thrombocytopenia . [ 1 ]


Nonthrombocytopenic purpura has been reported after smoking mentholated cigarettes. [ 2 ]


Examples/causes include:


Occupational skin diseases  are ranked among the top five occupational diseases in many countries. [ 1 ]


Contact Dermatitis  due to irritation is  inflammation  of the skin which results from a contact with an irritant. [ 2 ]  It has been observed that this type of  dermatitis  does not require prior sensitization of the  immune system . There have been studies to support that past or present  atopic dermatitis  is a risk factor for this type of  dermatitis . [ 3 ]  Common irritants include detergents, acids, alkalies, oils, organic solvents and reducing agents. [ 4 ]


Clinical manifestations of the contact dermatitis are also modified by external factors such as environmental factors (mechanical pressure, temperature, and humidity) and predisposing characteristics of the individual (age, sex, ethnic origin, preexisting skin disease, atopic skin diathesis, and anatomic region exposed. [ 5 ]


Another occupational skin disease is glove-related hand  urticaria ,  believed to be caused by repeated wearing and removal of the gloves. It has been reported as an occupational problem among the health care workers. The reaction is caused by the latex or the  nitrile  present in the gloves. [ 6 ]


The acute form of this dermatitis develops on exposure of the skin to a strong irritant or caustic chemical. This exposure can occur as a result of  accident  at a  workplace  . The irritant reaction starts to increase in its intensity within minutes to hours of exposure to the irritant and reaches its peak quickly. After the reaction has reached its peak level, it starts to heal. This process is known as decrescendo phenomenon. [ 7 ]  The most frequent potent irritants leading to this type of dermatitis are acids and alkaline solutions. [ 8 ]  The symptoms include redness and swelling of the skin along with the formation of blisters.


The chronic form occurs as a result of repeated exposure of the skin to weak irritants over long periods of time. [ 9 ]


Prevention measures include avoidance of the irritant through its removal from the workplace or through technical shielding by the use of potent irritants in closed systems or automation, irritant replacement or removal  [ 10 ]  and personal protection of the workers. Low quality evidence exists for the effectiveness of certain therapies and their ability to specifically prevent hand skin irritation in the workplace. The limited evidence that does exist suggests that moisturizers used alone or in combination with a barrier cream can result in a clinically beneficial effect in the long or short-term primary prevention of occupational irritant hand dermatitis. [ 11 ]


An  omphalolith , also known as a  umbolith ,  omphalith , [ 1 ]   navel stone , [ 2 ]  or  umbilical concretion [ 3 ]  is a  periumbilical  mass that may form due to the accumulation of  sebum  and  keratin . [ 4 ]  The colour is black or brown, and may be related to the skin type of the patient. [ 2 ]  It may resemble a  malignant melanoma . [ 5 ] [ page needed ]  It may be caused by poor hygiene, [ 6 ] : 121   and may form in retracted navels in  obese  people. [ 3 ]


The name was derived from the Greek words  omphalos  ( Greek :  ομφαλός ), meaning  navel , and  lithos  ( Greek :  λίθος ), meaning  stone . [ 3 ]


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


Penile discharge  is fluid that comes from the  urethra  at the end of the  penis  that is not  urine ,  pre-ejaculate  or  semen . [ 2 ] [ 3 ]


Common causes include infections due to  gonorrhea ,  chlamydia , or  trichomoniasis . [ 3 ]  In gonorrhea the discharge may be white, yellow, or green. [ 4 ] [ 5 ]


A swab of the discharge is usually performed. [ 5 ]


Treatment depends on the cause. Spread of infection is reduced by also  treating sexual contacts . [ 6 ]


Risk factors include being sexually active men under the age of 25, having a recent new sexual partner, or having unprotected sex. [ 6 ]


Penile discharge is liquid from the  urethra  at the end of the penis that is not urine or semen. [ 2 ]  The dripping of clear fluid ( pre-ejaculate ) when sexually excited is normal. [ 2 ]


There may be pain or burning when passing urine, soreness inside the penis or feeling of wanting to pass urine frequently. [ 6 ]


Common causes include infections due to  gonorrhea ,  chlamydia , or  trichomoniasis . [ 3 ]


Other causes include:


A swab of the discharge is usually performed. [ 5 ]  Other investigations may include tests for HIV, hepatitis and syphilis. [ 6 ]


Men who have sex with men may also need to have throat and rectal swabs. [ 6 ]


Treatment depends on the cause and any antibiotic prescribed depends on which infection is found. [ 6 ]  Spread of infection is reduced by  informing sexual partners  so that they can also be treated, and not having sex (including oral or anal) until tests are completed and seven days have passed after treatment. [ 6 ]


Risk factors include being sexually active men under the age of 25, having a recent new sexual partner, unprotected sex (without a condom), or having the presence of any sexually transmitted infection. [ 6 ]


Prolactin-inducible protein  also known as  gross cystic disease fluid protein 15  (GCDFP-15),  extra-parotid  glycoprotein  (EP-GP),  gp17   seminal actin-binding protein  (SABP)  or  BRST2  is a  protein  that in humans is encoded by the  PIP   gene . [ 5 ] [ 6 ] [ 7 ]  It is upregulated by  prolactin  and  androgens  and downregulated by  estrogen .


The protein has a physiological function in regulation of water transport mainly in apocrine glands in the axilla, vulva, eyelid and ear canal, serous cells of the submandibular salivary gland, serous cells of the submucosal glands of the bronchi, and accessory lacrimal glands  as well as cutaneous eccrine glands. [ 8 ]  It is also found in  amniotic fluid  and  seminal fluid .


PIP has the ability to bind  immunoglobulin G (IgG), IgG-Fc, CD4-T cell receptor suggesting a wide range of immunological functions. [ 9 ] [ 10 ]  PIP also binds to  AZGP1 . [ 10 ]  PIP exerts  aspartyl proteinase  activity able to cleave  fibronectin . [ 11 ] [ 12 ]


PIP can bind different species of bacteria showing highest affinity to streptococci thus playing a role in non-immune defense of the body against pathogenic bacterial strains. [ 13 ] [ 14 ]


Mitogenic effect of PIP was observed on both normal and malignant breast epithelial cells. [ 15 ]