Confluent and reticulated papillomatosis during pregnancy

Insulinemia joacã un rol cheie în dezvoltarea leziunilor de acanthosis negricans.

Common Skin Problems During Pregnancy

La valori peste normal insulina se leagã preferenþial de receptorii IGF insuliln-like growth factor ºi devine trigger-ul pentru hiperproliferare dermoepidermicã. Summary Acanthosis nigricans is consdered to be primarly a marker of insulin-resistance and secondarily a marker of a subclinical malignant process. The serum level of insulin plays a confluent and reticulated papillomatosis during pregnancy role in the development of AN lesions.

When it reaches levels beyond normal, insulin binds preferentially to IGF insulin-like growth factor and becomes the trigger for epidermal and dermal proliferation. Un procent important din cei bolnavi vor dezvolta în cursul vieþii leziuni cutanate.

Pentru unele dintre leziunile cutanate, legãtura cu diabetul este bine stabilitã sau foarte probabilã dermopatia diabeticã, bulele diabetice, reducerea mobilitãþii articulare, necrobioza lipoidicã, acanthosis nigricans ; pentru altele, asocierea cu Diabetes mellitus is a common chronic disorder theat affects all age groups, irrespective of the socio-economic status.

Many DM patients will develop skin lesions during their lifetime. Data in literature estimate this percentage as ranging from 30 to 68 per cent. Acanthosis nigricans AN este considerat, în primul rând, un marker cutanat al insulinorezistenþei ºi în mod secundar, al prezenþei unui proces malign cu evoluþie subclinicã. Se manifestã clinic sub forma unor plãci pigmentare verucoase localizate flexural, cu un caracter catifelat la palpare. Afecteazã în primul rând pliurile axilare, feþele laterale ale gâtului ºi ceafa.

Ulterior, leziunile pot fi localizate confluent and reticulated papillomatosis during pregnancy la nivel genital, perineal, pe coapse, sâni, dosul articulaþiilor interfalangiene, ariile flexurale ale genunchilor ºi coatelor.

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Rareori, erupþia poate deveni generalizatã sau pot apãrea determinãri ale mucoaselor. Interesarea mucoaselor se manifestã ca acantoza ºi papilomatoza la nivelul pleoapelor, conjunctivei, buzelor, mucoasei orale, faringiene, esofagiene, laringiene sau anogenitale, cu tulburãri funcþionale secundare. Etiopatogenie Etiologia modificãrilor cutanate din AN rãmâne neclarã.

Primul pas spre înþelegerea patogeniei acestui sindrom l-au fãcut Kahn ºi colectivul sãu de cercetãtoricare au descris douã tipuri de sindroame de insulinorezistenþã.

Tipul A, prezent la femei cu AN, hiperandrogenism ºi virilizare, este caracterizat prin anomalii ale receptorilor insulinici.

Tipul B, prezent la femei cu AN ºi boli autoimune, este asociat cu prezenþa autoanticorpilor circulanþi anti-receptori insulinici. Insulinemia joacã un rol cheie în dezvoltarea leziunilor de AN. La nivele normale ale insulinei serice, aceasta se leagã preferenþial de receptorii clasici, pe când la niveluri crescute, insulina se leagã preferenþial de receptorii IGF insulin-like growth factorreprezentând trigger-ul pentru proliferare. Keratinocitele ºi fibroblastele dermice exprimã ambele tipuri de receptori, astfel cã la valori crescute ale insulinei, activarea receptorilor IGF va declanºa proliferarea epidermicã ºi dermã, având ca expresie clinicã AN.

Acanthosis nigricans AN is first and foremost considered a skin marker of insulin resistance and, secondly, of the presence of a malign process with subclinical evolution. Its clinical manifestation consists in flexural verrucous pigmentary scales of velvety touch.

REFERATE GENERALE GENERAL REPORTS ILIESCU PASTOREL IUSTIN* Rezumat. Summary

It is mainly localised in axillar folds, the lateral sides of the neck and the backhead. Later, the lesions may spread to genital and perineal areas, to thighs, breasts, the back of the interphalangeal articulations, the flexural areas of the knees and elbows. Seldom confluent and reticulated papillomatosis during pregnancy eruption may generalize or affect the mucosae.

The the latter case, it takes the form of acanthosis and papillomatosis, affecting the eyelids, the conjunctiva, the lips, the oral, pharyngeal, esophageal, laryngeal or anogenital mucosae, and is accompanied by secondary functional disorders.

Ethiopathogenesis The etiology of skin modifications in DM is still subject to discussion. The first step towards the understanding of the pathogenesis of this syndrome was made by Kahn and collaboratorswho described two types of insulin resistance. Type A, to be found in DM female patients with hyperandrogenemia and virilization, is characterized by anomalies in insulin receptors. Type B, present in DM female patients with autoimmune diseases, is associated with insulin antireceptor circulating autoantibodies [3].

Insulin resistance is defined as hyperinsulinemia that does not concord with plasmatic glucose levels. Insulinemia plays a key role in DM lesions.

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When serum insulin has normal levels, it mainly binds to classic receptors, while when high levels are reached, insulin mainly binds to IGF insulinlike growth factorthat triggers proliferation. Dermic keratinocytes and fibroblasts express both types of receptors, so that in high levels of insulin, the activation of IGF factors shall actuate the epidermic and dermic proliferation that clinically manifests as AN [6]. Rolul etiologic al androgenilor este sugerat de ameliorarea leziunilor de AN la unele femei sub tratament antiandrogenic.

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În alte studii, însã, nu s-a citat ameliorarea leziunilor de AN ºi nici a insulino-rezistenþei, ci doar a hirsutismului, în caz de sindrom de insulino-rezistenþã de tip A, dupã tratament anti-androgenic. Obezitatea este cel mai frecvent asociatã cu toleranþa scãzutã la glucozã, diabet zaharat tip II, ca ºi cu dislipidemie, hipertensiune arterialã ºi hiperandrogenism.

Studiile genetice sugereazã cã AN, valorile insulinei serice a jeun, ca ºi DZ tip II sunt sub puternice influenþe pleiomorfe.

Lawrence-Seip, sd. Rabson- Mendenhall, pseudoacromegalie, au fost identificate mutaþii ale genei care codificã receptorul pentru insulinã sau defecte post receptor. Dupã înlãturarea chirurgicalã a tumorii maligne, s-a înregistrat revenirea la normal a acestor valori. A fost descrisã o formã idiopaticã de boalã, cu debut de la naºtere sau de la vârste fragede, cu caracter familial ºi transmitere probabil autosomal recesivã, cu penetranþã variabilã.

confluent and reticulated papillomatosis during pregnancy

AN prevalence in females with hyperandrogenemia is estimated to 5 to 29 per cent. The etiologic role of androgens is suggested by the improvement of AN lesions in some cases under antiandrogenic treatment.

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However, other studies have not concluded as to the amelioration of AN lesions, nor of insulin resistance, but only of the hirsuitism in type A insulin-resistant syndrome following the antiandrogenic treatment [14]. Hiperinsulinemia is almost always present in obsese patients. Obesity is most frequently associated with low tolerance to glucose, to type II diabetes mellitus, as well as to dyslipidemia, arterial hypertension and hyperandrogenemia.

Genetic studies suggest that AN, serum insulin values a jeun and DM type II are stongly influenced by pleiomorphs confluent and reticulated papillomatosis during pregnancy. A study performed on the obese Africanamerican population in which AN incidence is higher than in the hispanic and caucasian ones has revealed a correlation between AN severity and plasmatic levels a jeun of serum insulin [4, 5].

In other cases of insulin resistance, such as the Lawrence-Seip and Rabson-Mendenhall syndromes or pseudoacromegalia, mutations in the insulin receptor codifying gene or post-receptor defects have been highlighted [7]. As to AN association with neoplasia, researches have shown increased urinary values of transforming growth factor-alfa TGFaprobably of tumoral origin, and a higher presence of EGF factors epidermal growth factor in the lesional skin.

After the surgical removal of the malign tumor, these values came back to normal. Researchers have described an idiopathic form of the disease, starting at birth or early age, with genetic character, probable recessive autosomal transmission and variable penetration [8]. Clinical aspect When it sets in, confluent and reticulated papillomatosis during pregnancy characteristic aspect detoxifiere cu zer this disorder is that of dirty skin, due to the presence of greyish-brown verrucous flexural scales of velvety touch.

Pigmentation is followed 4 urmatã de hipertrofie, papilomatozã ºi accentuarea desenului cutanat. Localizãrile erupþiei sunt, în ordinea frecvenþei: axilã, ceafã, laterocervical, faþa internã a coapselor, organele genitale externe, scrotul, plicile antecubitala ºi poplitee, faþa, perineul ºi ombilicul.

Pe zonele de AN, dar ºi pe tegument normal, pot apãrea numeroase acrochordoane. Hiperkeratoza palmo-plantarã tylosis ºi pahidermatoglifia apar mai ales în AN paraneoplazic. Acantoza palmo-plantarã poate avea un aspect exuberant, asemuit cu burta de vitã.

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Tot în formele paraneoplazice sunt mai frecvente determinãri ale mucoaselor, manifestate ca îngroºare ºi papilomatozã cu hiperpigmentare minimalã. De cele mai multe ori acanthosis nigricans precede diagnosticul tumorii primare. De obicei, aceasta are agresivitate mare sau este deja într-un stadiu inoperabil. AN poate fi acompaniatã ºi de alte semne clinice sugestive pentru malignitate semnul Leser-Trelat, papilomatoza floridã cutanatã. Asocierile frecvente ale AN sunt enumerate în tabelul 1 2.

Sorted by frequency, AN chiefly affects the axillae, the back of the neck, the lateral sides of the cervix, the inside of thighs, the external genital organs, the groin, the antecubital and popliteal foldsm the face, the perineum and the navel.

On AN areas, but also on the normal tegument, numerous acrochordons may appear. Palmoplantar hyperkeratosis tylosis and pachydermatoglyphia mainly occur in paraneoplasic AN. Palmo-plantar acanthosis can take an exuberant form, resembling that of a cow belly. Mucosa delimitations are also more frequent in paraneoplasic forms of the condition and manifest as skin thickening and papillomatosis with minimal hyperpigmentation.

In most cases, acanthosis nigricans precedes the diagnosis of primary tumor. It is ususally very aggressive or already unoperable. AN can also be accompanied by other clinical markers that suggest malignity, such as the Leser- Trelat sign or florid confluent and reticulated papillomatosis during pregnancy papillomatosis. Alte neoplazii: endocrine carcinoid, feocromocitom, neoplasm tiroidianpulmonare cancer bronhoalveolar, cu celule mici, cu celule scuamoasereno-urinare tumora Wilms, carcinom de vezicã urinarãlimfoame inclusiv mycosis fungoidmelanom malign Niacina, corticosteroizi, contraceptive orale, acid fusidic topic, dietilstilbestrol, testosteron, somatotropinã Sd.

Bloom, sd. Prader-Willi, sd. Lawrence- Seip, sd. Crouzon, sd. Beare-Stevenson, acromegalie Lupus, dermatomiozita, sclerodermie autoimmune Association "Benign" Obesity Malignity Drugs Syndromes Comments Skin nevus form; possibly associated with multiple other nevi; posible autosomal dominant transmission Most common disorder type; insulinresistant; high incidence of type II DM Prevalence in adults, seldom in children; sudden occurrence and fast evolution; mainly as intra-abdominal adenocarcinoma 45 to 61 per cent.

Other neoplasias: endocrine carcinoid, pheochromocytoma, thyroid neoplasmpulmonary bronchoalveolar carcinoma, with small cells, with squamous cellsrenal-urinary Wilms' tumor, urinary vesicle carcinomalymphomae including fungoid mycosismalign melanoma Niacin, corticosteroids, oral contraceptives, topic fusidic acid, diethylsilbestrol, confluent and reticulated papillomatosis during pregnancy, somatotropin Bloom, Prader-Willi, Lawrence-Seip, polycystic ovarian syndrome, Crouzon, Beare-Stevenson, acromegalia Auto-immune Lupus, dermatomyositis, scleroderma diseases confluent and reticulated papillomatosis during pregnancy Au fost descrise mai multe variante clinice de AN: tipul acral, cu afectare a dosului mâinilor, picioarelor ºi falangelor, mai frecvent la persoanele cu fototip închis; tipul unilateral, cu distribuþie nevoidã poate persista nemodificat sau poate progresa spre forma bilateralã ; tipul mixt, care sumeazã caracteristici ale tuturor formelor descrise mai sus.

Culoarea brunã a leziunilor este datã de aggressive cancer gene ºi nu de hipermelanozã, care este minimã sau absentã.

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La nivelul mucoaselor, aspectul poate fi de parakeratoza focalã, acantozã mai accentuatã ºi hiperplazia epiteliului papilar. Diagnosticul pozitiv se stabileºte relativ uºor pe baza aspectului clinic. Examenul histopatologic este rareori necesar. În rare cazuri, leziunile pun problema diagnosticului diferenþial.

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Astfel, leziunile unilaterale pot necesita diferenþierea de un nev pigmentar nev Becker, nev epidermic, nev melanocitar. Boala Dowling-Degos este o genodermatozã rarã, care debuteazã la adultul tânãr, cu pigmentare de aspect macular ºi reticulat în axile ºi perineal.

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Histologic, lipseºte papilomatoza ºi sunt prezente proiecþii epidermice filiforme care implicã ºi infundibulul folicular. Diskeratoza congenitã este o altã genodermatozã rarã, la care hiperpigmentarea de aspect reticulat este asociatã cu atrofie unghialã, hiperkeratoza ºi atrofie palmo-plantarã, leucokeratozã a mucoaselor cu potenþial crescut de malignizare. Debutul este în decada a doua confluent and reticulated papillomatosis during pregnancy viaþã. Tot în categoria hiperpigmentarilor reticulate intra ºi papilomatoza confluentã ºi reticulatã Gougerot-Carteaud, la care localizarea tipicã este medio-toracicã intermamar, interscapular.

Leziunile pigmentare conflueazã central ºi au aspect reticulat în periferie. Au fost descrise asocieri de AN, obezitate, hiperinsulinism ºi papilomatozã Gougerot-Carteaud. Uneori, stadiul incipient al unui micosis fungoid poate mima aspect de AN unilateral Several clinical variants of AN have been described: the acral type, that affects the back of the hands, feet and phalanges, more frequently in persons with dark complexion; the unilateral type, with nevoid distribution it can persist confluent and reticulated papillomatosis during pregnancy or evolve towards the bilateral type ; the mixed type, that sums up characteristics of the above mentioned forms [1].

Histopathology Irrespective of the clinical form the condition takes, the anatomo-pathological aspect is the same, characterized by hyperkeratosis, whorled acanthosis and papillamatosis. The brown colour is given by hyperkeratosis, and not by hypermelanosis, which has minimal values or is completely absent.

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At the level of mucosae, the aspect can be confluent and reticulated papillomatosis during pregnancy of focal parakeratosis, more acute acanthosis and the hyperplasia of the papillary epithelium. Positive diagnosis is relatively confluent and reticulated papillomatosis during pregnancy established by taking into account the clinical aspect. Lesions can seldom require differential diagnosis. For example, lesions need to be differentiated from a pigmentary nevus Becker nevus, epidermic nevus, melanocitary nevus.

The Dowling-Degos disease is a rare genodermatosis that occurs in young adults and takes a macular and reticular aspect in the axillae and the perineal area. Histologically, papillomatosis is absent, while filiform epidermal warts also involve a follicular confluent and reticulated papillomatosis during pregnancy. Congenital dyskeratosis is another rare genodermatosis, in which reticular hyperpigmentation is associated with nail atrophy, hyperkeratosis and palmo-plantar atrophy, mucous leucokeratosis with increased risk of malignifying.

It usually occurs in the second decade of life. Also confluent and reticulated papillomatosis during pregnancy reticular hyperpigmentation is the Gougerot-Carteaud confluent and reticulated papillomatosis, typically localised in the thorax intermammarily and interscapularly.

Pigmentary lesions centrally converge and have a peripheral reticulate aspect. Studies have shown associations with AN, obesity, hyperinsulinism and Gougerot-Carteaud papillomatosis. Sometimes, in the incipeint stage, the fungoid mycosis can resemble in aspect the unilateral AN [12]. As to mucosal lesions, their association with 6 În ceea ce priveºte leziunile mucoaselor, asocierea cu leziuni cutanate tipice de AN face de multe ori uºoarã încadrarea lor.

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Am amintit de diskeratoza congenitã; leziuni papilomatoase ale mucoasei orale întâlnim ºi în boala Cowden sd. Acestea se grupeazã frecvent perioral, perinazal, periauricular ºi pot sugera clinic verucile plane.

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Mucoasa oralã prezintã papule confluate cu aspect de pietre de pavaj ºi fibropapiloame multiple. Hiperpigmentarea cutanatã este, însã, predominant acralã. Piostomatita vegetantã apare în asociere cu leziuni cutanate ulcerative ºi vegetante ºi este consideratã o variantã de pyoderma gangrenosum.

Mucoasa oralã este sediul unor leziuni pustuloase vegetative, apãrute frevent în contextul bolii inflamatorii cronice intestinale boala Crohn, colita hemoragicã.

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Au mai fost citate în diagnosticul diferenþial al leziunilor de pe mucoase: granulomatoza Wegener tabloul clinic este complex ºi histologia tipicã de leziune granulomatoasãca ºi alte genodermatoze extrem de rare proteinoza lipoidicã, pachionichia congenitã, diskeratoza ereditarã benignã.

În ceea ce priveºte diagnosticul etiopatogenic, examenul clinic general aduce date orientative, iar investigaþiile de laborator ºi paraclinice vor completa tabloul bolii. În faþa unui pacient treatment for papilloma on foot, este de aºteptat sã depistãm o insulino-rezistenþã.

Se vor determina valorile a jeun ale glicemiei ºi insulinemiei. Deºi nu toate persoanele cu insulino-rezistenþã prezintã AN ºi valori crescute ale insulinemiei a jeun, o valoare crescutã a insulinei a jeun neconcordanta cu valorile glicemiei a jeun la un pacient cu AN este, categoric, o dovadã de insulino-rezistentã. În faþa unui pacient normo sau subponderal, la care AN a avut un debut brusc ºi o evoluþie rapidã, ne gandim la AN ca sindrom paratypical AN skin lesions makes it easy to label.

We have already mentiones congenital dyskeratosis; papillomatous lesions of the oral mucosa are also encountered in Cowden disease multiple hamartoma syndromecharacterized by multiple skin trichilemmomas.

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