Alergia na nikiel
Patofizjologia i mechanizm

Alergia na nikiel jest najczęstszą przyczyną alergicznego kontaktowego zapalenia skóry (ACD) w krajach uprzemysłowionych i stanowi klasyczny przykład nadwrażliwości typu IV, z kluczową rolą limfocytów T. Proces uczulenia przebiega w dwóch fazach: sensytyzacji, gdzie jony niklu penetrują skórę, indukując produkcję cytokin prozapalnych (TNF-α, IL-1, TSLP) i aktywację komórek dendrytycznych, oraz fazy wywołania, w której ponowna ekspozycja na nikiel prowadzi do aktywacji limfocytów T CD4+ i CD8+ i rozwoju objawów klinicznych w ciągu 24-72 godzin. Mechanizmy immunologiczne obejmują prezentację haptenów niklu przez MHC klasy I i II, aktywację receptorów Toll-podobnych (szczególnie TLR4) oraz szlak kinazy p38 MAPK, z kluczową rolą fosforylacji MKK6 w komórkach dendrytycznych. Czynniki genetyczne, takie jak mutacje genu filagryny i polimorfizmy TNF-α (genotyp TNFA308 A/A i GA), zwiększają podatność na alergię. Diagnostyka opiera się na testach płatkowych oraz, w przypadku systemowej alergii kontaktowej na nikiel (SNAS), na testach prowokacji doustnej z 0,6 mg siarczanu niklu po 4-6 tygodniach diety eliminacyjnej.

  1. Mechanizm uczulenia na nikiel
    1. Fazy rozwoju alergii na nikiel
    2. Rola komórek dendrytycznych i limfocytów T
    3. Mechanizmy molekularne prezentacji niklu
  2. Rola receptorów Toll-podobnych w alergii na nikiel
    1. Szlak kinazy MAPK w alergii na nikiel
  3. Genetyczne uwarunkowania alergii na nikiel
    1. Rola receptora TSLP w alergii na nikiel
  4. Alergia na nikiel systemowa (SNAS)
    1. Mechanizm reakcji systemowej po spożyciu niklu
  5. Diagnostyka alergii na nikiel
  6. Leczenie i profilaktyka alergii na nikiel
    1. Dieta niskonieklowa i hiposensytyzacja
  7. Powiązania z innymi schorzeniami
  8. Podsumowanie najnowszych badań
    1. Kolejne rozdziały

Mechanizm uczulenia na nikiel

Alergia na nikiel stanowi najczęstszą przyczynę alergicznego kontaktowego zapalenia skóry (ACD) w krajach uprzemysłowionych. Jest to klasyczny przykład reakcji nadwrażliwości typu IV (opóźnionej), w której kluczową rolę odgrywają limfocyty T. Mechanizm patogenetyczny alergii na nikiel jest złożony i obejmuje kilka etapów, które prowadzą do rozwoju odpowiedzi immunologicznej123.

Fazy rozwoju alergii na nikiel

Uczulenie na nikiel przebiega w dwóch głównych fazach: sensytyzacji (indukcji) i wywołania (elicytacji)1:

Faza sensytyzacji – jest to pierwszy kontakt organizmu z niklem, który prowadzi do rozwinięcia nadwrażliwości. W tej fazie następuje penetracja jonów niklu przez skórę, co prowadzi do produkcji cytokin prozapalnych (TNF-α i IL-1), TSLP oraz chemokin. Związki te aktywują i stymulują migrację komórek dendrytycznych skóry (DC) obładowanych haptenowanymi białkami do regionalnych węzłów chłonnych1. Należy podkreślić, że nikiel sam w sobie nie jest immunogenny, ale staje się taki po połączeniu z białkami nośnikowymi skóry, tworząc kompleks haptenowy23.

Faza wywołania – następuje po ponownym kontakcie z niklem. Kolejna ekspozycja na ten sam hapten prowadzi do szybkiej aktywacji uczulonych limfocytów T, które produkują mediatory zapalne w miejscu kontaktu, wywołując typowe objawy alergicznego kontaktowego zapalenia skóry12. Objawy kliniczne pojawiają się w ciągu 24-72 godzin od ekspozycji, co jest charakterystyczne dla nadwrażliwości typu opóźnionego1.

Rola komórek dendrytycznych i limfocytów T

Komórki dendrytyczne skóry, w tym komórki Langerhansa (LC), odgrywają kluczową rolę w prezentacji antygenu niklu limfocytom T1. Po aktywacji przez nikiel, komórki te przechodzą proces dojrzewania, charakteryzujący się zwiększoną ekspresją cząsteczek kostymulujących CD80, CD83, CD86 oraz MHC klasy II1. Następnie migrują do regionalnych węzłów chłonnych, gdzie prezentują kompleks nikiel-białko naiwnym limfocytom T CD4+1.

W alergii na nikiel uczestniczą zarówno limfocyty CD4+ jak i CD8+. Limfocyty CD8+ wykazują głównie profil cytokin typu 1, podczas gdy limfocyty CD4+ mogą wydzielać bardziej zróżnicowane cytokiny, z przewagą komórek Th1 i mniejszą liczbą komórek Th21. Najnowsze badania wskazują również na udział komórek Th17 w procesie zapalnym2.

Mechanizmy molekularne prezentacji niklu

Istnieją różne mechanizmy, poprzez które nikiel może indukować reakcję alergiczną1:

  1. Nikiel wiąże się z białkiem nośnikowym w przestrzeni pozakomórkowej, a następnie jest przetwarzany i prezentowany przez komórki prezentujące antygen (APC) w kontekście cząsteczki MHC klasy II, co aktywuje limfocyty CD4+.
  2. Nikiel przenika do komórki, gdzie wiąże się z białkami wewnątrzkomórkowymi, a następnie jest prezentowany w kontekście cząsteczki MHC klasy I, co aktywuje limfocyty CD8+.
  3. Nikiel może tworzyć „most” łączący cząsteczkę MHC z receptorem TCR na limfocycie, nie wypełniając właściwego miejsca wiązania antygenu, co przypomina mechanizm działania superantygenów1.

Rola receptorów Toll-podobnych w alergii na nikiel

Przełomowe odkrycie w zrozumieniu mechanizmu alergii na nikiel dotyczy roli receptora Toll-podobnego 4 (TLR4)12. Badania wykazały, że ludzki TLR4 odgrywa kluczową rolę w rozwoju alergii kontaktowej na nikiel1. Myszy z deficytem TLR4 wykazujące ekspresję transgenicznego ludzkiego TLR4 rozwijały nadwrażliwość kontaktową na nikiel, podczas gdy myszy z ekspresją mysiego TLR4 nie1.

Aktywacja TLR4 przez nikiel prowadzi do aktywacji czynnika jądrowego NF-κB, kinazy p38 oraz czynnika regulatorowego interferonu 3, co skutkuje indukcją wielu cytokin prozapalnych wyzwalających reakcję alergiczną1. To wyjaśnia, dlaczego Ni2+, w przeciwieństwie do innych alergenów kontaktowych, bezpośrednio wyzwala aktywację ludzkich komórek dendrytycznych zależną od NF-κB2.

Szlak kinazy MAPK w alergii na nikiel

Istotną rolę w patogenezie alergii na nikiel odgrywa szlak kinazy białkowej aktywowanej mitogenami (MAPK), szczególnie kinaza p381. Badania wykazały, że aktywacja komórek dendrytycznych skóry poprzez kinazę p38 MAPK wyzwala odpowiedź immunologiczną zależną od limfocytów T w modelu alergii na nikiel1.

W kaskadzie sygnałowej MAPK w komórkach dendrytycznych, nikiel silnie fosforyluje kinazę kinazy MAP (MKK6), co prowadzi do zwiększonej aktywacji komórek dendrytycznych2. Kinaza p38 MAPK jest aktywowana przez kinazę upstream (MKK6 lub MKK3), a następnie przenoszona do jądra komórkowego, gdzie fosforyluje cząsteczki docelowe1.

Badania eksperymentalne silnie sugerują, że fosforylacja MKK6 w komórkach dendrytycznych skóry jest pierwszym istotnym bodźcem dla wystąpienia reakcji alergicznej na nikiel2. Co ciekawe, manipulacja genem MKK6 w komórkach dendrytycznych może kontrolować alergię na nikiel, co otwiera nowe możliwości terapeutyczne34.

Genetyczne uwarunkowania alergii na nikiel

Mimo że czynniki środowiskowe mają kluczowe znaczenie w patogenezie alergii na nikiel, badania sugerują również udział czynników genetycznych1. U wielu pacjentów z atopowym zapaleniem skóry lub alergicznym kontaktowym zapaleniem skóry na nikiel stwierdzono wadliwą formę genu filagryny1.

Filagryna jest istotnym białkiem strukturalnym warstwy rogowej naskórka, a jej mutacje wpływają na integralność tej warstwy, co ułatwia przenikanie jonów metali i sprzyja reakcjom alergicznym1. Badania z użyciem spektroskopii Ramana wykazały różnice biochemiczne w skórze pacjentów z alergią na nikiel w porównaniu ze zdrową skórą, co może być związane z niedoborami filagryny lub naturalnego czynnika nawilżającego2.

Ponadto badania wskazują na istnienie polimorfizmu genu TNF-α, który może wpływać na podatność na rozwój polisensytyzacji kontaktowej1. Obecność genotypu TNFA308 A/A i GA wiąże się ze zwiększoną produkcją TNF-α, która jest potężnym aktywatorem keratynocytów i może działać jako marker zwiększonej podatności na kontaktową polisensytyzację2.

Rola receptora TSLP w alergii na nikiel

Najnowsze badania na modelach mysich wykazały, że zwiększona ekspresja receptora limfopoetyny zrębu grasicy (TSLPR) na komórkach dendrytycznych odgrywa kluczową rolę w wyzwalaniu odpowiedzi alergicznej na nikiel12. Wyniki te sugerują, że alergia na nikiel jest wyzwalana przez interakcję między komórkami nabłonkowymi a komórkami układu odpornościowego, zapośredniczoną przez TSLP/TSLPR2.

Alergia na nikiel systemowa (SNAS)

Oprócz klasycznego alergicznego kontaktowego zapalenia skóry, nikiel może wywoływać również systemową alergię kontaktową (Systemic Nickel Allergy Syndrome, SNAS)1. SNAS charakteryzuje się objawami żołądkowo-jelitowymi (wzdęcia, biegunka lub zaparcia, wymioty, nudności, ból brzucha) oraz objawami skórnymi1.

Patofizjologia SNAS nie jest jeszcze w pełni wyjaśniona, ale wiąże się z interakcją między dwoma typami odpowiedzi limfocytów T (Th1 i Th2)1. W przypadku SNAS, spożycie niklu w diecie powoduje połączenie niklu z białkami jelitowymi2. Zdolność niklu do wywoływania reakcji alergicznej wynika z obecności dwóch niesparowanych elektronów w jego orbicie peryferyjnej, co umożliwia tworzenie wiązań organicznych z peptydami lub białkami, prowadząc do powstania kompleksów antygenowych odpowiedzialnych za reakcje alergiczne3.

Badania immunohistochemiczne biopsji jelitowych pobranych po doustnym podaniu 10 mg niklu u pacjentów z SNAS wykazały naciek komórek CD4+ w blaszce właściwej dwunastnicy i w nabłonku, ze znacznym zmniejszeniem liczby limfocytów CD8+ w nabłonku, spowodowanym apoptozą wywołaną silnym wyzwaniem antygenowym1.

Mechanizm reakcji systemowej po spożyciu niklu

Spożycie niklu przez osoby uczulone wyzwala szereg zmian w układzie odpornościowym, które mogą prowadzić do rozwoju reakcji klinicznych1. Spożycie niklu powoduje zmniejszenie krążących limfocytów CD8+, CD45RO+ i CLA+, co może prowadzić do migracji pamięciowych limfocytów T CD8+ do tkanek2.

Ponadto spożycie niklu w diecie zwiększa poziom interleukiny 5 (IL-5) w surowicy. W rezultacie następuje szybki wzrost namnażania eozynofilów, które są białymi krwinkami pomagającymi zwalczać alergie i infekcje3.

Badania wykazały również, że reakcja zaostrzenia po doustnym przyjęciu niklu może obejmować mechanizmy zarówno typu IV (komórkowe), jak i III (humoralne) reakcji nadwrażliwości1. W miejscach dawnych testów płatkowych po doustnym przyjęciu antygenu zaobserwowano obecność rozproszonych okołonaczyniowych infiltratów komórkowych składających się z makrofagów, komórek tucznych, limfocytów T i komórek dendrytycznych OKT6+1.

Diagnostyka alergii na nikiel

Podstawowym narzędziem diagnostycznym w alergii na nikiel są testy płatkowe12. Test polega na naklejeniu na skórę, zwykle na plecach, taśmy z komorami testowymi zawierającymi alergeny i, w razie potrzeby, inne podejrzane substancje1.

Wyniki testu odczytuje się po 48 i 72 godzinach2. Jeśli występuje alergia na nikiel, skóra pod płatkiem z niklem będzie wykazywać stan zapalny po usunięciu płatka lub w ciągu kilku dni po jego usunięciu1.

Złotym standardem do diagnozowania SNAS jest test prowokacji doustnej (Oral Provocation Test, OPT), zwany również „wyzwaniem doustnym niklu” (Nickel Oral Challenge, NOC), który można wykonać dopiero po 4-6 tygodniach diety bez niklu1. Test prowokacji polega na podaniu kapsułki zawierającej talk jako placebo, a następnie, po godzinie, kapsułki zawierającej 0,6 mg siarczanu niklu2.

Leczenie i profilaktyka alergii na nikiel

Najskuteczniejszą metodą łagodzenia objawów alergii na nikiel jest unikanie kontaktu z alergenem12. Osoby uczulone na nikiel powinny unikać codziennych przedmiotów zawierających nikiel i unikać długotrwałego kontaktu skóry z tym metalem3.

Jeśli nie można całkowicie uniknąć kontaktu, pomocne mogą być środki bezpieczeństwa, takie jak rękawiczki lub odzież ochronna4. W rzadkich przypadkach zawartość niklu w żywności może zaostrzać egzemę u pacjentów z ciężką alergią na nikiel5.

Leczenie alergii na nikiel jest głównie objawowe i obejmuje stosowanie miejscowych kortykosteroidów lub innych leków przeciwzapalnych1. W przypadku ciężkich reakcji może być konieczne zastosowanie kortykosteroidów ogólnoustrojowych, cyklosporyny i innych leków immunosupresyjnych, a także terapii PUVA1.

Dieta niskonieklowa i hiposensytyzacja

W przypadku systemowej alergii na nikiel (SNAS) stosuje się dietę niskonieklową, ale ponieważ nikiel jest pierwiastkiem wszechobecnym, bardzo trudno jest zapewnić całkowicie wolną od niklu dietę12.

Mimo kontrowersji, niektóre badania potwierdziły rolę i korzyści z hiposensytyzacji doustnym niklem w alergii na nikiel12. Zaobserwowano, że tolerancję doustną na uczulenie na nikiel można uzyskać poprzez karmienie siarczanem niklu osób wrażliwych na nikiel2.

Sugerowany mechanizm doustnej hiposensytyzacji u osób wrażliwych na nikiel to stymulacja produkcji komórek T supresorowych przez nadmiar antygenu33. Jednak ze względu na niejednoznaczne dowody i kontrowersje, skuteczność diety niskonieklowej i hiposensytyzacji wymaga dalszych badań1.

Powiązania z innymi schorzeniami

Coraz więcej badań sugeruje związek między alergią na nikiel a chorobami autoimmunologicznymi1. Dokładna zależność między tymi schorzeniami nie jest jasna, ale zarówno alergie, jak i choroby autoimmunologiczne wiążą się z podobną aktywnością układu odpornościowego2.

Badania wykazały, że systemowa alergia na nikiel może być czynnikiem ryzyka rozwoju autoimmunologicznej choroby tarczycy3. Inne badania wykazały, że osoby z alergią na nikiel po narażeniu doustnym były szczególnie narażone na rozwój chorób autoimmunologicznych4.

Międzynarodowa Akademia Medycyny Jamy Ustnej i Toksykologii (IOAMT) donosi, że metal może powodować stan zapalny, który może prowadzić do rozwoju zarówno chorób alergicznych, jak i autoimmunologicznych5. Przegląd badań z 2020 roku wykazał, że metale mogą hamować lub uszkadzać układ odpornościowy, co może prowadzić do alergii i/lub autoimmunizacji, w zależności od podatności pacjenta1.

Badania sugerują również związek między alergią na nikiel a zespołem jelita drażliwego (IBS)1. Coraz więcej dowodów sugeruje, że pacjenci z IBS mają zmniejszoną funkcję bariery jelitowej, a niektóre formy IBS są związane z zapaleniem jelita o niskim stopniu nasilenia2. Podobnie alergia na nikiel wiąże się z dysregulacją układu odpornościowego z przeważającym działaniem immunosupresyjnym3.

Podsumowanie najnowszych badań

Najnowsze badania nad molekularnymi mechanizmami alergii na nikiel skupiają się na identyfikacji potencjalnych celów terapeutycznych1. Jednym z obiecujących kierunków jest manipulacja genem MKK6 w komórkach dendrytycznych, co może stanowić dobrą strategię terapeutyczną w alergii na nikiel1.

Inne badania identyfikują semaforynę 3A (Sema3A) jako potencjalny cel w zapobieganiu i leczeniu alergii na nikiel1. Wykazano, że ekspresja Sema3A jest zwiększona w tkance ucha myszy z alergią na nikiel oraz w keratynocytach mysich stymulowanych NiCl22. Sema3A może promować rozwój alergii na metale i powinna być badana jako potencjalny cel w zapobieganiu i leczeniu alergii na metale3.

Badania nad składem mikrobiomu jelitowego u pacjentów z alergią na nikiel również zyskują na znaczeniu1. Według wstępnych wyników z literatury, zidentyfikowano korelację między pacjentami wrażliwymi na nikiel, składem mikrobiomu jelitowego a otyłością2. Jednak dane obecne w literaturze związane z tym zagadnieniem są nadal ograniczone i kontrowersyjne, dlatego rola mikrobiomu jelitowego w odniesieniu do pacjentów z SNAS wymaga dalszych badań3.

Ponadto badania nad mechanizmami reaktywności krzyżowej na różne jony metali rzucają nowe światło na podobieństwa w odpowiedzi immunologicznej między blisko spokrewnionymi pierwiastkami w układzie okresowym1. Nikiel (Ni2+) i pallad (Pd2+) mają podobieństwa fizykochemiczne, co pozwala im tworzyć podobne kompleksy i wywoływać te same modyfikacje w białkach obecnych w skórze lub kompleksie pMHC2.

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  1. 10.04.2026
  2. www.leksykon.com.pl

Materiały źródłowe

  • #1 Molecular Mechanisms of Nickel Allergy
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4783936/
    Allergic contact hypersensitivity to metals is a delayed-type allergy. […] Nickel is the most frequent cause of metal allergy. […] Here, the immunological and molecular mechanisms of metal allergy are described based on the findings of previous studies, including those that were recently published. […] Nickel ions released from various alloys are potent allergens or haptens that can trigger skin inflammation. […] They penetrate the skin and activate epithelial cells that produce various cytokines or chemokines. […] The reaction follows complex immune responses that involve the activation of antigen-presenting cells (APCs) and T cells. […] Some cytokines activate APCs, such as Langerhans cells (LCs) or dendritic cells (DCs). […] Activated APCs migrate to the draining lymph nodes where they present the allergens or haptens to naive CD4-positive T cells.
  • #1 Nickel allergy – Wikipedia
    https://en.wikipedia.org/wiki/Nickel_allergy
    Nickel allergy results in a skin response after the skin comes in contact with an item that releases a large amount of nickel from its surface. […] The pathophysiology of systemic nickel allergy syndrome (SNAS) is not well understood. The clinical course is determined by an immunological interplay between two types of T cells (Th1 and Th2 responses). […] The pathophysiology is divided into induction elicitation phases. Induction is the critical phase (immunological event) when skin contact to nickel results in antigen presentation to the T cells, and T cell duplication (cloning) occurs. […] The determining factor in sensitization is exposure of significant amounts of „free nickel”. […] Although ACD has been considered a Th1 predominate process, recent studies highlight a more complex picture. In Ni-ACD other cells are involved including: Th17, Th22, Th1/IFN and the innate immune responses consistent with toll-like receptor 4.
  • #1 Molecular Mechanisms of Nickel Allergy
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4783936/
    A complex mechanism of metal allergy. […] The sensitization phase begins after nickel exposure to the skin. […] Nickel penetration into the skin results in the production of proinflammatory cytokines (TNF- and IL-1), TSLP, and chemokines, which induce activation and migration of haptenated protein-loaded epidermal and dermal DCs through afferent lymph to the draining lymph nodes. […] Particularly in humans, nickel directly activates the TLR4 pathway in DCs. […] In the draining lymph nodes, haptenated-peptide presentation results in the proliferation, activation and subsequent differentiation of hapten-specific T cells. […] Secretion of cytokines in the draining lymph nodes during the sensitization phase contributes to efficient hapten-specific T cell activation, proliferation, and differentiation.
  • #1 Nickel Allergy – ECARF
    https://www.ecarf.org/en/information-portal/allergies-overview/nickel-allergy/
    Nickel allergy is a contact allergy (also referred to as type IV or delayed type hypersensitivity). Unlike immediate hypersensitivities (such as pollen, insect venom and most food allergies), the reaction in delayed type hypersensitivity occurs some time after exposure. Following contact with the allergen, it can take 24 to 72 hours before the first symptoms appear. This delay is caused by what are called helper T cells (medical term: T-lymphocytes). […] In a contact allergy, the helper T cells remember a presumably harmless substance like nickel. If the skin is then re-exposed to the environmental substance, the helper T cells transform in the upper skin layers and cause an inflammatory reaction. The time delay also occurs because the cells need to travel along this path. […] True symptoms in the form of allergic eczema triggered by nickel or other substances develop in 8.0% of German adults over the course of their lifetime.
  • #1 Molecular Mechanisms of Nickel Allergy
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4783936/
    At the end of this phase, primed specific T cells migrate out of the lymph nodes to the skin. […] In the elicitation phase, the subsequent application of the same hapten leads to uptake by cells, which is presented to the recirculating hapten-specific T cells. […] The activated T cells produce inflammatory cytokines and chemokines at the site of exposure that promote an allergic reaction, leading to the development of characteristic skin lesions. […] Several studies have shown that the activation of p38 mitogen-activated protein kinase in dermal DCs is required to trigger a T cell-mediated immune response in a mouse model of nickel allergy. […] Ni-activated epithelial DCs or LCs exhibit the upregulation of CD80, CD83, CD86, and MHC class II. […] Moreover, nickel plays an important role in the maturation and activation of immature LCs or DCs in the skin via phosphorylated MAP kinase kinase 6 (MKK6).
  • #1 Allergic contact dermatitis: Immune system involvement and distinctive clinical cases | Allergologia et Immunopathologia
    https://www.elsevier.es/en-revista-allergologia-et-immunopathologia-105-articulo-allergic-contact-dermatitis-immune-system-S030105461100200X
    Human hapten-specific CD8+ T cells show a type 1 cytokine profile, whereas the cytokine released by CD4+ T cells are more variable, with a predominance of Th1 cells and a lower number of Th2 cells. […] The involvement of Th17 cells has been observed in some recent studies. […] Increased IL-18 serum levels have been found in patients with allergic contact dermatitis. This pro-inflammatory cytokine is involved in the Th1 response and immune cell infiltration into the tissues, so it probably has a role in the induction of contact dermatitis, together with IL-12 and IFN-gamma.
  • #1 Mechanisms of nickel allergy
    http://www.radoslawspiewak.net/2007-5a.htm
    Nickel allergy constitutes a serious health problem of modern societies. Hypersensitivity to this metal is found in 13% adults and 8% children. Various mechanisms of inducing nickel allergy are possible, which is also reflected in the different clinical pictures. Nickel can Induce allergic reaction in 3 different ways: 1) It binds to carrier protein in the extracellular space and subsequently is processed and presented by antigen presenting cell (APC) in the context of MHC class II molecule, which activates CD4+ lymphocytes, 2) Ni penetrates into the cell where it binds to intracellular proteins, and subsequently it is presented in the context of MHC class I molecule, which activates CD8+ lymphocytes, 3) Ni can „bridge” MHC molecule together with the TCR receptor on lymphocyte without actually filling the antigen-binding site, which is in analogy to superantigens.
  • #1 Molecular Mechanisms of Nickel Allergy
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4783936/
    Therefore, Ni-stimulated DCs prime activate T cells to induce skin inflammation at the site of exposure to nickel. […] However, the injection of short interfering (si) RNAs targeting MKK6 prevents a hypersensitive reaction after Ni immunization in a mouse model, suggesting that manipulating MKK6 in DCs might be a good therapeutic strategy for nickel allergy. […] Human toll-like receptor (TLR) 4 has been shown to play a crucial role in the development of contact allergy to nickel. […] Ni-induced activation of TLR4 leads to the activation of nuclear factor (NF)-B, p38, and interferon regulatory factor 3, resulting in the induction of multiple proinflammatory cytokines that trigger an allergic response. […] These findings explain why Ni2+, but not other contact allergens, directly triggers NF-B-dependent activation of human DCs.
  • #1 Nickel allergy tracked to a single receptor | BioEd Online
    https://www.bioedonline.org/news/nature-news-archive/nickel-allergy-tracked-single-receptor/
    A specific immune-system mechanism underlies the skin rashes caused by contact with nickel, one of the world’s most common allergens. […] Activating this receptor, called Toll-like receptor 4 (TLR4), generates a 'danger signal’ that promotes inflammation causing itching, tenderness, swelling and rashes on the skin and recruits other immune cells such as T cells to the area. […] No one has ever proposed that a single receptor could mediate the initial inflammatory response that leads to an allergic reaction to nickel, explains Matthias Goebeler, a dermatologist at the University of Giessen in Germany, who led the study. […] The study not only solves the long-standing mystery of how nickel causes an allergic reaction, but also „opens up another avenue of thought” about how Toll-like receptors work, says Anthony Gaspari, a dermatologist at the University of Maryland in Baltimore. […] The work suggests it may be possible to treat nickel allergy with a topical blocker of TLR4, Gaspari says.
  • #1 Molecular Mechanisms of Nickel Allergy
    https://www.mdpi.com/1422-0067/17/2/202
    Allergic contact hypersensitivity to metals is a delayed-type allergy. Although various metals are known to produce an allergic reaction, nickel is the most frequent cause of metal allergy. […] Nickel ions released from various alloys are potent allergens or haptens that can trigger skin inflammation. They penetrate the skin and activate epithelial cells that produce various cytokines or chemokines. The reaction follows complex immune responses that involve the activation of antigen-presenting cells (APCs) and T cells. […] Human toll-like receptor (TLR) 4 has been shown to play a crucial role in the development of contact allergy to nickel. TLR4-deficient mice expressing transgenic human TLR4 developed contact hypersensitivity to nickel, whereas those expressing mouse TLR4 did not. […] Using a mouse model, a recent study showed that the increased expression of the thymic stromal lymphopoietin (TSLP) receptor (TSLPR) on DCs plays a key role in triggering an allergic response to nickel. […] The pathogenesis and mechanisms of the allergic response is highly complex, and many patients develop refractory disease. Because metal allergy is caused by materials used in products that are common in our daily life, chances of triggering the onset of allergic reactions are high.
  • #1 A Novel DC Therapy with Manipulation of MKK6 Gene on Nickel Allergy in Mice | PLOS One
    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0019017
    Although the activation of dermal dendritic cells (DCs) or Langerhans cells (LCs) via p38 mitogen-activated protein kinase (MAPK) plays a crucial role in the pathogenesis of metal allergy, the in vivo molecular mechanisms have not been identified and a possible therapeutic strategy using the control of dermal DCs or LCs has not been established. […] The activation of dermal DCs via p38 MAPK triggered a T cell-mediated allergic immune response in this model. In the MAPK signaling cascade in DCs, Ni potently phosphorylated MAP kinase kinase 6 (MKK6) following increased DC activation. […] The cooperative action between T cell activation and MKK6-mediated DC activation by Ni played an important role in the development of Ni allergy. […] DC activation by Ni played an important role in the development of Ni allergy. Manipulating the MKK6 gene in DCs may be a good therapeutic strategy for dermal Ni allergy.
  • #1 A Novel DC Therapy with Manipulation of MKK6 Gene on Nickel Allergy in Mice | PLOS One
    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0019017
    p38 MAPK is activated by an upstream kinase (MKK6 or MKK3) and then translocated into the nucleus where target molecules are phosphorylated by p38 MAPK. […] Our experiments using a Ni allergy model strongly suggest that MKK6 phosphorylation in dermal DCs is the first important trigger for the onset of an allergic response to Ni. […] Our in vivo experiments demonstrated that manipulating the MKK6 gene of DCs could control Ni allergy.
  • #1 Genetics of Nickel Allergic Contact Dermatitis
    https://www.medscape.com/viewarticle/564081
    Nickel sulfate is the most frequently detected cause of allergic contact dermatitis in the world; the prevalence of nickel allergic contact dermatitis is between 8 and 11% in the general female population. […] Although it is well recognized that environmental factors are important in the pathogenesis of this dermatitis, some investigators have hypothesized that genetic factors are important as well. […] Several researchers have hypothesized that genetics may also play a role in susceptibility to and development of nickel hypersensitivity. […] To the best of our knowledge, contact dermatitis from topically applied allergens has never been conclusively linked to genetic factors in humans. […] The purpose of this review is to summarize animal and human studies evaluating genetic factors in the development of ACD from nickel.
  • #1 Allergic Contact Dermatitis: Practice Essentials, Background, Pathophysiology
    https://emedicine.medscape.com/article/1049216-overview
    Approximately 3000 chemicals are well documented as specific causes of allergic contact dermatitis. […] Compounds must be less than 500 d for efficient penetration through the stratum corneum barrier, which is the water-impermeable outer layer of the skin. Small organic molecules that are chemically reactive (chemical sensitizers) bind with self-proteins to generate immunogenic neoantigens through a process termed haptenization. […] Many patients with atopic dermatitis or allergic contact dermatitis to nickel harbor a defective form of the filaggrin gene. […] Haptens activate Toll-like receptors (TLRs) and activate innate immunity. […] Haptens or haptenated self-proteins are recognized by innate immune mechanisms in the skin, and this leads to the elaboration of a number of proinflammatory mediators, including interleukin (IL)1.
  • #1 Use of Raman spectroscopy in the analysis of nickel allergy
    https://www.spiedigitallibrary.org/journals/journal-of-biomedical-optics/volume-18/issue-6/061206/Use-of-Raman-spectroscopy-in-the-analysis-of-nickel-allergy/10.1117/1.JBO.18.6.061206.full
    Raman spectra of the skin of subjects with nickel allergy are analyzed and compared to the spectra of healthy subjects to detect possible biochemical differences in the structure of the skin that could help diagnose metal allergies in a noninvasive manner. […] Even though metal allergy is mainly an environmental disorder, null mutations in the filaggrin gene complex were recently found to be associated with nickel allergy and dermatitis. […] Because filaggrin gene mutations affect the integrity of the stratum corneum, these mutations allow the permeation of metal ions favoring allergic reactions. […] Nickel allergy has been related to filaggrin gene mutations, it is possible that the biochemical composition of nickel allergy patients is different from that of healthy subjects. […] In this work, the Raman spectra of skin of subjects with nickel allergy is analyzed and compared to the spectra of skin of healthy subjects to detect possible biochemical differences in the structure of the skin and develop a noninvasive method to diagnose metal allergies. […] The difference in Raman spectra can be explained by biochemical differences in the skin, which might be due to filaggrin or natural moisturizing factor deficiencies which have been linked to different types of skin allergy.
  • #1 Role of TNF-alpha polymorphism in patients with nickel allergy: a marker of susceptibility to contact polysensitization
    https://www.europeanreview.org/article/11025
    Nickel allergy is the most frequent contact allergy in the industrialized country. In allergic contact dermatitis after the presentation of haptenated peptides by resident or newly recruited skin cells, activated CD8+ T cells release IFN- and TNF-, these cytokines are potent activator of keratinocytes. The role of specific cytokines in nickel allergy is not yet fully elucidated. The adenine nucleotide at position -308 in the promoter region of the TNFA gene is associated with an increased production of TNF-, that is a potent activator of keratinocytes. […] The carriage of the TNFA308 A/A and GA genotype may act as a marker of enhanced susceptibility to contact polysensitization, indicating that TNF- is a key regulator of the initiation of delayed-type hypersensitivity reactions, the polymorphism seems to be not enough for the development of nickel monosensitization.
  • #1 Molecular Mechanisms of Nickel Allergy
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4783936/
    Using a mouse model, a recent study showed that the increased expression of the thymic stromal lymphopoietin (TSLP) receptor (TSLPR) on DCs plays a key role in triggering an allergic response to nickel. […] These results suggest that nickel allergy is triggered by a TSLP/TSLPR-mediated interaction between epithelial and immune cells. […] Molecular mechanisms of metal allergy need to be determined to develop novel therapeutic strategies.
  • #1 Systemic Nickel Allergy Syndrome (SNAS) – Research Article
    https://www.gavinpublishers.com/article/view/systemic-nickel-allergy-syndrome-taking-stock-of-medical-nutrition-therapy-snas-and-nutrition
    Nickel is a ubiquitous metal present in different products such as soil, food, and water. Being ubiquitous, it is difficult to avoid contact in everyday life. Moreover, it could be the cause for Nickel allergy, Allergic Contact Dermatitis, and Systemic Nickel Allergy Syndrome (SNAS Allergy). […] Nickel may induce other clinical manifestations besides ACD, like Systemic Contact Dermatitis (SCD) and Systemic Nickel Allergy Syndrome (SNAS), which have to be considered and are required to be addressed for best care. All in all, sensitization to Nickel may occur by means of different mechanisms: skin contact with Nickel, inducing Allergic Contact Dermatitis (ACD); Nickel ingested from food, provoking Systemic Nickel Allergy Syndrome (SNAS) and Systemic Contact Dermatitis (SCD), with gastrointestinal symptoms and/or chronic dermatopathy.
  • #1 Systemic Nickel Allergy Syndrome (SNAS) – Research Article
    https://www.gavinpublishers.com/article/view/systemic-nickel-allergy-syndrome-taking-stock-of-medical-nutrition-therapy-snas-and-nutrition
    Systemic Nickel Allergy Syndrome (SNAS) manifestation is instead characterized by gastrointestinal symptoms including bloating, diarrhea or constipation, vomiting, nausea, abdominal pain, and cutaneous signs. […] It is well documented that Nickel is a strong hapten with a good chemical reactivity and a high molecular weight and hydrophobicity, which facilitates its penetration through the skin and mucous membranes. Nickel combines with some skin proteins of the skin and establishes an antigenic complex, which is recognized as non-self by the immune system triggering an immune response. […] In the specific case of SNAS, dietary Nickel ingestion causes Nickel conjugation to intestinal proteins. Nickel’s ability to induce an allergic reaction is due to the presence of two unpaired electrons in its peripheral orbit, which allow an organic bond with peptides or proteins leading to antigenic complexes responsible for allergic reactions.
  • #1 Systemic Nickel Allergy Syndrome (SNAS) – Research Article
    https://www.gavinpublishers.com/article/view/systemic-nickel-allergy-syndrome-taking-stock-of-medical-nutrition-therapy-snas-and-nutrition
    Even though the specific SNAS immune-reaction is still unclear; some Immunological studies have demonstrated that SNAS is characterized by the involvement of a complex cytokine network with production and release Th2 other than Th1 cytokines, typical of a type IV immune reaction, besides IFN-γ, IL-2, and TNF-α increase. […] Immunohistochemistry of intestinal biopsies, taken after 10 mg Nickel oral challenges in SNAS patients, demonstrated an infiltration of CD4+ cells in the duodenal lamina propria and in the epithelium with a strong reduction of epithelial CD8+ lymphocytes, due to apoptosis induced by the strong antigen challenge. […] The histopathology of the flare-up eczema in patients with SNAS after oral Nickel challenge is similar to the reactions caused by allergic contact dermatitis, but because SCD starts from few hours up to 1-2 days after Nickel ingestion, more than one type of hypersensitivity mechanism may be involved.
  • #1 Azthena logo with the word Azthena
    https://www.news-medical.net/health/Nickel-Allergy.aspx
    Nickel ingestion through the diet in nickel-sensitive people triggers a series of changes in the immune system that can lead to the development of clinical reactions. […] Nickel ingestion causes a decrease in circulating CD8+, CD45RO+, and CLA+ blood lymphocytes, which can lead to the migration of CD8+ memory T cells into the tissues. […] Dietary ingestion of nickel also increases interleukin (IL)-5 levels in the serum. As a result, there is a rapid increase in the reproduction of eosinophils, which are white bloods cells that help fight allergies and infections. […] The mechanism of absorption of ingested nickel in the body is not fully understood yet, though it has been proved that vitamin C and iron are capable of decreasing the absorption of dietary nickel. Therefore, iron-rich foods and vitamin C supplements can help reduce the amount of nickel absorbed by the body.
  • #1 Systemic Nickel Allergy Syndrome (SNAS) – Research Article
    https://www.gavinpublishers.com/article/view/systemic-nickel-allergy-syndrome-taking-stock-of-medical-nutrition-therapy-snas-and-nutrition
    Gold standard for SNAS diagnosis is based on an Oral Provocation Test (OPT), called also Nickel “Oral Challenge” (NOC) that can be performed only after 4-6 weeks of a Nickel-free diet. […] An observed rapid cutaneous response following oral Nickel provocation suggests a complex interplay within SNAS between Type IV (cellular) and III (humoral) hypersensitivity reactions. […] The provocation test consists of administering a capsule containing talc as placebo, followed by a capsule containing 0.6 mg of Nickel sulphate, 1 hour later. […] As far as “Nickel Free diet” (N-F diet) concerns, the practical limitation is that there’s no standard dietetic protocol universally accepted and recommended. […] Since Nickel is a ubiquitous trace metal, it’s very hard to provide a complete N-F diet, therefore usually N-F diet ends up to be a low Nickel diet.
  • #1 Pathogenesis of orally induced flare-up reactions at old patch sites in nickel allergy | Abstract | Acta Dermato-Venereologica
    https://www.medicaljournals.se/acta/content/abstract/10.2340/0001555565298304
    The flare-up reaction of old patch test sites following oral intake of antigen have been shown to be site and antigen specific reactions. […] Before oral challenge, small scattered perivascular cell infiltrates consisting of macrophages, mast cells, T-lymphocytes, and OKT6+ dendritic cells were found in old patch test sites. […] In early and strong flare-up reactions combined with systemic toxicoderma-like reactions, polymorphonuclear leukocytes and lysed granular fragments from these cells were prominent. […] In slower flare-up reactions with little systemic involvement, T-lymphocytes predominated. […] We conclude that cells, probably macrophages, which are able to secrete inflammatory mediators promoting chemotaxis for polymorphonuclear leukocytes and/or T-lymphocyte proliferation, may play an important role in initiation of the flare-up reaction.
  • #1 Nickel Allergy: Epidemiology, Pathomechanism, Clinical Patterns, …: Ingenta Connect
    https://www.ingentaconnect.com/contentone/ben/emiddt/2020/00000020/00000007/art00005
    Patch testing represents the gold standard for the diagnosis of ACD from nickel. […] Treatment includes avoidance of contact with products containing nickel and the patients education about the possible use of alternative products. […] Nickel allergy is a relevant issue of public health with significant personal, social, and economic impact. […] This review summarizes epidemiology, pathomechanism, clinical patterns, treatment, and prevention programs.
  • #1 Nickel Allergy – ECARF
    https://www.ecarf.org/en/information-portal/allergies-overview/nickel-allergy/
    A patch test is used to diagnose a contact allergy. For this test, adhesive tape with test chambers is applied onto the skin, usually on the back. The test chambers contain allergens and, if necessary, other suspected substances. The test results are read after 48 and 72 hours. […] The most effective method for relieving symptoms is to avoid the allergy-triggering substance. People who are allergic to nickel should stay away from everyday objects containing nickel and avoid prolonged skin contact. If contact cannot be avoided completely, safety measures such as gloves or protective clothing can help. […] In rare cases, the nickel content in food can exacerbate eczema in patients with a severe nickel allergy.
  • #1 Nickel allergy | UM Health-Sparrow
    https://www.uofmhealthsparrow.org/departments-conditions/conditions/nickel-allergy
    The first step in treating nickel allergy is avoiding contact with the metal. There’s no cure for nickel allergy. Once you develop a sensitivity to nickel, you’ll develop a rash (contact dermatitis) whenever you come into contact with the metal. […] During a patch test, very small quantities of potential allergens (including nickel) are applied to your skin and covered with small patches. The patches remain on your skin for two days before the doctor removes them. If you have a nickel allergy, the skin under the nickel patch will be inflamed when the patch is removed or in the days after removal of the patch.
  • #1
    https://www.healthychildren.org/English/health-issues/conditions/allergies-asthma/Pages/Nickel-Allergy.aspx
    For children allergic to nickel, anything from jeans with metal buttons to handheld electronics can cause a red, itchy rash. Called nickel-allergic contact dermatitis, an allergy to nickel affects an estimated 1.1 million children in the United States. […] An allergy to nickel is not life-threatening, but it can be uncomfortable enough to get in the way of a child’s sleep and cause them to miss school. […] The allergy also has been linked to severe hand eczema later in adulthood. […] The skin allergic reaction to nickel looks like eczema. Signs and symptoms include an itchy rash with redness, swelling, scaling and possibly a crusty appearance. […] Once children become sensitive to nickel, gradually worsening rashes may develop each time they are exposed to nickel again. […] Although there is no cure for nickel allergy, here are a few ways to help prevent reactions: […] Nickel allergy has been linked with nail polish from a bottle that contains nickel metal shaker balls. […] In addition to recommending ways to help avoid exposure to nickel, your pediatrician may recommend short-term treatment with a steroid ointment or another anti-inflammatory medication.
  • #1 +Bioline International Official Site (site up-dated regularly)
    http://www.bioline.org.br/request?dv07116
    Nickel is poorly absorbed when ingested in typical diets. Only 1-10% of the ingested dietary nickel is absorbed; the mechanism of absorption is unclear. Following absorption, nickel is transported in blood bound to serum albumin. Nickel is not significantly accumulated by any tissue in the body, although the thyroid and adrenal glands have relatively high nickel concentrations in comparison to other tissues. Most of the absorbed nickel is excreted by the kidneys as low-molecular weight complexes. Nickel is also lost through sweat and bile. […] Nickel is one of the commonest sensitizers all over the world. Once sensitized, the sensitization tends to persist for many years, often life-long. Therefore, nickel allergy shows a chronic recurring course. Different types of treatments have been recommended – wet dressing, topical steroids, systemic steroids, cyclosporine and other immunosuppressives, PUVA therapy, etc. The result of treatment of such nickel eczema is mostly unsatisfactory as the relapse rate is high. This is because humans are continuously exposed to nickel in the environment, be it at home or workplace.
  • #1 Relationship between nickel allergy and diet – Indian Journal of Dermatology, Venereology and Leprology
    https://ijdvl.com/relationship-between-nickel-allergy-and-diet/
    Nickel allergy is a chronic and recurring skin problem; females are affected more commonly than males. Nickel allergy may develop at any age. Once developed, it tends to persist life-long. Nickel in the diet of a nickel-sensitive person can provoke dermatitis. […] The degree and pattern of nickel allergy varies: (c) Some patients develop vesicular type of hand eczema following the ingestion of nickel in diet. […] Studies have confirmed the role and benefit of hyposensitization with oral nickel in nickel allergy. It has been noted that oral tolerance to nickel sensitization can be obtained by feeding with nickel sulfate in nickel sensitive individual, and this has opened a new area of investigation for the treatment of nickel allergy. The suggested mechanism for oral hypo-sensitization in nickel-sensitive individual is the stimulation of the suppresser T-cell production by antigen excess.
  • #1 Systemic nickel hypersensitivity and diet: myth or reality? – European Annals of Allergy and Clinical Immunology
    https://www.eurannallergyimm.com/systemic-nickel-hypersensitivity-and-diet-myth-or-reality/
    With respect to respiratory disorders, the role of food nickel and the effectiveness of a dietary treatment have been assumed but not proven. […] In fact, the usefulness of a therapeutic low-nickel diet is controversial: rare, if not exceptional, and limited to very sporadic cases of SCD. […] Conclusion: an evaluation of the data presented by medical literature about SNAS and its relationship with oral nickel does not allow to draw final conclusions. In the absence of genuine certainty we can only conclude that further and broader studies, more rigorously conducted, are needed.
  • #1 Nickel Allergy and Autoimmune Disease
    https://www.verywellhealth.com/nickel-allergy-and-autoimmune-disease-5198646
    A nickel allergy could make you more susceptible to autoimmune disease, according to research. Nickel allergy is sometimes called nickel allergic contact dermatitis (NACD). […] Researchers are looking into common underlying mechanisms to understand how the two may be related. […] The precise relationship between these illnesses is unclear, but allergies and autoimmune diseases both involve similar immune-system activity. Several studies have noted a link between nickel allergies and autoimmune disease. […] A 2014 paper suggested that a systemic nickel allergy is a risk factor for developing autoimmune thyroid disease. Another study found that people with nickel allergy from oral exposure were especially likely to have an autoimmune disease. […] The International Academy of Oral Medicine and Toxicology (IOAMT) reported that metal can cause inflammation. And that inflammation can lead to the development of both allergic and autoimmune diseases.
  • #1 Nickel Allergy and Autoimmune Disease
    https://www.verywellhealth.com/nickel-allergy-and-autoimmune-disease-5198646
    A 2020 review of research found that metals may suppress or damage the immune system. That may lead to allergies and/or autoimmunity, depending on your susceptibility. […] Research suggests that metal allergies, in general, may be especially linked to autoimmune conditions that affect connective tissues, such as rheumatoid arthritis, Sjgrens disease, systemic lupus erythematosus, spondyloarthritis, scleroderma, and polymyalgia rheumatica. […] Nickel allergy may lead to autoimmune disease. Nickel is widely used in everyday items plus medical devices and implants. Allergies develop after prolonged exposure causes the immune system to misfire. Autoimmune disease is caused by the immune system mistaking something harmless for something threatening.
  • #1 Irritable Bowel Syndrome and Nickel Allergy: What Is the Role of the Low Nickel Diet?
    https://www.jnmjournal.org/journal/view.html?doi=10.5056/jnm16027
    Irritable bowel syndrome (IBS) is characterized by chronic abdominal pain or discomfort accompanied by abnormal bowel movements. In sensitized subjects, ingested nickel (Ni) may induce gastrointestinal symptoms similar to IBS, in addition to typical systemic cutaneous lesions (systemic nickel allergy syndrome [SNAS]). A low nickel diet could improve the systemic manifestations. […] Growing evidence suggests that patients with IBS have decreased intestinal barrier function and that some forms of IBS are associated with low-grade intestinal inflammation. Similarly, Ni allergy is associated with immune system dysregulation with prevalent immunosuppressive action. In particular, Ni-sensitive patients with symptom recrudescence after Ni ingestion showed significant decrease of CD8+ and massive inflammatory infiltration of CD4+ CD45RO+ T lymphocytes in the duodenal lamina propria and epithelium as well as an involvement of Th2-type cytokines (IL-5 and IL-13).
  • #1 Semaphorin 3A: A potential target for prevention and treatment of nickel allergy | Communications Biology
    https://www.nature.com/articles/s42003-022-03641-0
    Metal allergy is one of the typical immune disorders encountered during the application of dental/medical materials and has a highly complex pathogenic mechanism. […] Herein, we show that Sema3A expression was upregulated in nickel (Ni) allergy-induced mouse ear tissue and in NiCl2-stimulated mouse keratinocytes. […] Our results demonstrate that Sema3A promotes the development of metal allergy and should be explored as a potential target for the prevention and treatment of metal allergy. […] We speculated that Sema3A, being a secretory protein, might function like cytokines or chemokines and may play a crucial role in both intercellular and intracellular communication, thereby influencing the process of metal allergy development. […] Sema3A may play a role in triggering or regulating the process of Ni allergy through p38 kinase activation and TNF- expression in keratinocytes.
  • #1 Systemic Nickel Allergy Syndrome (SNAS) – Research Article
    https://www.gavinpublishers.com/article/view/systemic-nickel-allergy-syndrome-taking-stock-of-medical-nutrition-therapy-snas-and-nutrition
    Many authors recommend the BraMaNi diet by Braga and Maccarinelli, developed to minimize additive content and vasoactive amines in foods. […] Adherence to a Nickel free diet is essential during the oral provocation test period to avoid false positive results. […] Nickel oral hyposensitization is a mechanism of immune tolerance in a Nickel-sensitized patient through the ingestion of low Nickel doses. […] According to preliminary results from the literature, a correlation between Nickel sensitive patients, gut microbiota composition, and obesity was identified. […] To date, data present in the literature related to this issue is still limited and controversial, and thus the role of gut microbiota related to SNAS patients must be further examined. […] At present, it is impossible to draw definite evidence-based recommendations about the nutritional support and management of SNAS. Nickel-free diets have been highly criticized for noncompliance and the inadequate intake of micronutrients.
  • #1 Immunological Mechanisms of Metal Allergies and the Nickel-Specific TCR-pMHC Interface
    https://www.mdpi.com/1660-4601/18/20/10867
    Cross-reactivity to different metal ions has been investigated in vivo by patch testing and in vitro by restimulation of metal-specific T cell clones. […] The wide variation in the frequencies of co-sensitized patients between different metal ions indicates that it is difficult to investigate the extent of T cell cross-reactivity by patch testing only. […] Cross-reactivity becomes likely with elements that are listed in close proximity in the PSE. Since Ni2+ and Pd2+ have physiochemical similarities, they can form similar complexes and thus trigger the same modifications in proteins present in the skin or pMHC.
  • #2 Nickel Allergy – StatPearls – NCBI Bookshelf
    https://www.ncbi.nlm.nih.gov/books/NBK557638/
    Nickel allergy is a type of allergic contact dermatitis. A nickel allergy is commonly encountered with jewelry, kitchen tools, and silverware. […] Allergic contact dermatitis represents the classic presentation of a T cell-mediated, delayed-type hypersensitivity response to exogenous agents. The initial step in the development of allergic contact dermatitis, as in nickel allergy, is hapten binding to a skin carrier protein. A hapten by itself is not immunogenic but becomes so after binding to a skin protein carrier. The hapten protein complex forms through covalent bonds between the hapten and amino acid side chains of target proteins within the skin. […] The complex ultimately produces the sensitization of T cells. Sensitized T cells encountering the antigen at any time later will then lead to the release of cytokines, which in turn leads to macrophage activation and produces the immune response. […] In summary, the sensitization process requires an initial exposure to allow the immune system to recognize the antigen later and lead to the immune response that causes ACD.
  • #2 Molecular Mechanisms of Nickel Allergy
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4783936/
    At the end of this phase, primed specific T cells migrate out of the lymph nodes to the skin. […] In the elicitation phase, the subsequent application of the same hapten leads to uptake by cells, which is presented to the recirculating hapten-specific T cells. […] The activated T cells produce inflammatory cytokines and chemokines at the site of exposure that promote an allergic reaction, leading to the development of characteristic skin lesions. […] Several studies have shown that the activation of p38 mitogen-activated protein kinase in dermal DCs is required to trigger a T cell-mediated immune response in a mouse model of nickel allergy. […] Ni-activated epithelial DCs or LCs exhibit the upregulation of CD80, CD83, CD86, and MHC class II. […] Moreover, nickel plays an important role in the maturation and activation of immature LCs or DCs in the skin via phosphorylated MAP kinase kinase 6 (MKK6).
  • #2 Allergic contact dermatitis: Immune system involvement and distinctive clinical cases | Allergologia et Immunopathologia
    https://www.elsevier.es/en-revista-allergologia-et-immunopathologia-105-articulo-allergic-contact-dermatitis-immune-system-S030105461100200X
    Human hapten-specific CD8+ T cells show a type 1 cytokine profile, whereas the cytokine released by CD4+ T cells are more variable, with a predominance of Th1 cells and a lower number of Th2 cells. […] The involvement of Th17 cells has been observed in some recent studies. […] Increased IL-18 serum levels have been found in patients with allergic contact dermatitis. This pro-inflammatory cytokine is involved in the Th1 response and immune cell infiltration into the tissues, so it probably has a role in the induction of contact dermatitis, together with IL-12 and IFN-gamma.
  • #2 Molecular Mechanisms of Nickel Allergy
    https://www.mdpi.com/1422-0067/17/2/202
    Allergic contact hypersensitivity to metals is a delayed-type allergy. Although various metals are known to produce an allergic reaction, nickel is the most frequent cause of metal allergy. […] Nickel ions released from various alloys are potent allergens or haptens that can trigger skin inflammation. They penetrate the skin and activate epithelial cells that produce various cytokines or chemokines. The reaction follows complex immune responses that involve the activation of antigen-presenting cells (APCs) and T cells. […] Human toll-like receptor (TLR) 4 has been shown to play a crucial role in the development of contact allergy to nickel. TLR4-deficient mice expressing transgenic human TLR4 developed contact hypersensitivity to nickel, whereas those expressing mouse TLR4 did not. […] Using a mouse model, a recent study showed that the increased expression of the thymic stromal lymphopoietin (TSLP) receptor (TSLPR) on DCs plays a key role in triggering an allergic response to nickel. […] The pathogenesis and mechanisms of the allergic response is highly complex, and many patients develop refractory disease. Because metal allergy is caused by materials used in products that are common in our daily life, chances of triggering the onset of allergic reactions are high.
  • #2 Molecular Mechanisms of Nickel Allergy
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4783936/
    Therefore, Ni-stimulated DCs prime activate T cells to induce skin inflammation at the site of exposure to nickel. […] However, the injection of short interfering (si) RNAs targeting MKK6 prevents a hypersensitive reaction after Ni immunization in a mouse model, suggesting that manipulating MKK6 in DCs might be a good therapeutic strategy for nickel allergy. […] Human toll-like receptor (TLR) 4 has been shown to play a crucial role in the development of contact allergy to nickel. […] Ni-induced activation of TLR4 leads to the activation of nuclear factor (NF)-B, p38, and interferon regulatory factor 3, resulting in the induction of multiple proinflammatory cytokines that trigger an allergic response. […] These findings explain why Ni2+, but not other contact allergens, directly triggers NF-B-dependent activation of human DCs.
  • #2 A Novel DC Therapy with Manipulation of MKK6 Gene on Nickel Allergy in Mice | PLOS One
    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0019017
    Although the activation of dermal dendritic cells (DCs) or Langerhans cells (LCs) via p38 mitogen-activated protein kinase (MAPK) plays a crucial role in the pathogenesis of metal allergy, the in vivo molecular mechanisms have not been identified and a possible therapeutic strategy using the control of dermal DCs or LCs has not been established. […] The activation of dermal DCs via p38 MAPK triggered a T cell-mediated allergic immune response in this model. In the MAPK signaling cascade in DCs, Ni potently phosphorylated MAP kinase kinase 6 (MKK6) following increased DC activation. […] The cooperative action between T cell activation and MKK6-mediated DC activation by Ni played an important role in the development of Ni allergy. […] DC activation by Ni played an important role in the development of Ni allergy. Manipulating the MKK6 gene in DCs may be a good therapeutic strategy for dermal Ni allergy.
  • #2 A Novel DC Therapy with Manipulation of MKK6 Gene on Nickel Allergy in Mice | PLOS One
    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0019017
    p38 MAPK is activated by an upstream kinase (MKK6 or MKK3) and then translocated into the nucleus where target molecules are phosphorylated by p38 MAPK. […] Our experiments using a Ni allergy model strongly suggest that MKK6 phosphorylation in dermal DCs is the first important trigger for the onset of an allergic response to Ni. […] Our in vivo experiments demonstrated that manipulating the MKK6 gene of DCs could control Ni allergy.
  • #2 Use of Raman spectroscopy in the analysis of nickel allergy
    https://www.spiedigitallibrary.org/journals/journal-of-biomedical-optics/volume-18/issue-6/061206/Use-of-Raman-spectroscopy-in-the-analysis-of-nickel-allergy/10.1117/1.JBO.18.6.061206.full
    Raman spectra of the skin of subjects with nickel allergy are analyzed and compared to the spectra of healthy subjects to detect possible biochemical differences in the structure of the skin that could help diagnose metal allergies in a noninvasive manner. […] Even though metal allergy is mainly an environmental disorder, null mutations in the filaggrin gene complex were recently found to be associated with nickel allergy and dermatitis. […] Because filaggrin gene mutations affect the integrity of the stratum corneum, these mutations allow the permeation of metal ions favoring allergic reactions. […] Nickel allergy has been related to filaggrin gene mutations, it is possible that the biochemical composition of nickel allergy patients is different from that of healthy subjects. […] In this work, the Raman spectra of skin of subjects with nickel allergy is analyzed and compared to the spectra of skin of healthy subjects to detect possible biochemical differences in the structure of the skin and develop a noninvasive method to diagnose metal allergies. […] The difference in Raman spectra can be explained by biochemical differences in the skin, which might be due to filaggrin or natural moisturizing factor deficiencies which have been linked to different types of skin allergy.
  • #2 Role of TNF-alpha polymorphism in patients with nickel allergy: a marker of susceptibility to contact polysensitization
    https://www.europeanreview.org/article/11025
    Nickel allergy is the most frequent contact allergy in the industrialized country. In allergic contact dermatitis after the presentation of haptenated peptides by resident or newly recruited skin cells, activated CD8+ T cells release IFN- and TNF-, these cytokines are potent activator of keratinocytes. The role of specific cytokines in nickel allergy is not yet fully elucidated. The adenine nucleotide at position -308 in the promoter region of the TNFA gene is associated with an increased production of TNF-, that is a potent activator of keratinocytes. […] The carriage of the TNFA308 A/A and GA genotype may act as a marker of enhanced susceptibility to contact polysensitization, indicating that TNF- is a key regulator of the initiation of delayed-type hypersensitivity reactions, the polymorphism seems to be not enough for the development of nickel monosensitization.
  • #2 Molecular Mechanisms of Nickel Allergy
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4783936/
    Using a mouse model, a recent study showed that the increased expression of the thymic stromal lymphopoietin (TSLP) receptor (TSLPR) on DCs plays a key role in triggering an allergic response to nickel. […] These results suggest that nickel allergy is triggered by a TSLP/TSLPR-mediated interaction between epithelial and immune cells. […] Molecular mechanisms of metal allergy need to be determined to develop novel therapeutic strategies.
  • #2 Systemic Nickel Allergy Syndrome (SNAS) – Research Article
    https://www.gavinpublishers.com/article/view/systemic-nickel-allergy-syndrome-taking-stock-of-medical-nutrition-therapy-snas-and-nutrition
    Systemic Nickel Allergy Syndrome (SNAS) manifestation is instead characterized by gastrointestinal symptoms including bloating, diarrhea or constipation, vomiting, nausea, abdominal pain, and cutaneous signs. […] It is well documented that Nickel is a strong hapten with a good chemical reactivity and a high molecular weight and hydrophobicity, which facilitates its penetration through the skin and mucous membranes. Nickel combines with some skin proteins of the skin and establishes an antigenic complex, which is recognized as non-self by the immune system triggering an immune response. […] In the specific case of SNAS, dietary Nickel ingestion causes Nickel conjugation to intestinal proteins. Nickel’s ability to induce an allergic reaction is due to the presence of two unpaired electrons in its peripheral orbit, which allow an organic bond with peptides or proteins leading to antigenic complexes responsible for allergic reactions.
  • #2 Azthena logo with the word Azthena
    https://www.news-medical.net/health/Nickel-Allergy.aspx
    Nickel ingestion through the diet in nickel-sensitive people triggers a series of changes in the immune system that can lead to the development of clinical reactions. […] Nickel ingestion causes a decrease in circulating CD8+, CD45RO+, and CLA+ blood lymphocytes, which can lead to the migration of CD8+ memory T cells into the tissues. […] Dietary ingestion of nickel also increases interleukin (IL)-5 levels in the serum. As a result, there is a rapid increase in the reproduction of eosinophils, which are white bloods cells that help fight allergies and infections. […] The mechanism of absorption of ingested nickel in the body is not fully understood yet, though it has been proved that vitamin C and iron are capable of decreasing the absorption of dietary nickel. Therefore, iron-rich foods and vitamin C supplements can help reduce the amount of nickel absorbed by the body.
  • #2 Nickel Allergy
    https://dermnetnz.org/topics/nickel-allergy
    Nickel allergy is one of the most common causes of contact allergic dermatitis. In affected individuals, dermatitis (also called eczema) develops in places where nickel-containing metal is touching the skin. […] Nickel allergy is diagnosed by the clinical history and by special allergy tests, patch tests. […] Unfortunately, desensitization with injections or pills is not possible so the allergy tends to persist long-term. […] It has been suggested that in nickel allergic people pompholyx may be due to nickel in the diet. Unfortunately it is not possible to avoid ingesting nickel as it is present in most foodstuffs. A low-nickel diet is only rarely helpful.
  • #2 Nickel Allergy – ECARF
    https://www.ecarf.org/en/information-portal/allergies-overview/nickel-allergy/
    A patch test is used to diagnose a contact allergy. For this test, adhesive tape with test chambers is applied onto the skin, usually on the back. The test chambers contain allergens and, if necessary, other suspected substances. The test results are read after 48 and 72 hours. […] The most effective method for relieving symptoms is to avoid the allergy-triggering substance. People who are allergic to nickel should stay away from everyday objects containing nickel and avoid prolonged skin contact. If contact cannot be avoided completely, safety measures such as gloves or protective clothing can help. […] In rare cases, the nickel content in food can exacerbate eczema in patients with a severe nickel allergy.
  • #2 Systemic Nickel Allergy Syndrome (SNAS) – Research Article
    https://www.gavinpublishers.com/article/view/systemic-nickel-allergy-syndrome-taking-stock-of-medical-nutrition-therapy-snas-and-nutrition
    Gold standard for SNAS diagnosis is based on an Oral Provocation Test (OPT), called also Nickel “Oral Challenge” (NOC) that can be performed only after 4-6 weeks of a Nickel-free diet. […] An observed rapid cutaneous response following oral Nickel provocation suggests a complex interplay within SNAS between Type IV (cellular) and III (humoral) hypersensitivity reactions. […] The provocation test consists of administering a capsule containing talc as placebo, followed by a capsule containing 0.6 mg of Nickel sulphate, 1 hour later. […] As far as “Nickel Free diet” (N-F diet) concerns, the practical limitation is that there’s no standard dietetic protocol universally accepted and recommended. […] Since Nickel is a ubiquitous trace metal, it’s very hard to provide a complete N-F diet, therefore usually N-F diet ends up to be a low Nickel diet.
  • #2 Nickel allergy: How to avoid exposure and reduce symptoms
    https://www.aad.org/public/diseases/eczema/insider/nickel-allergy
    Nickel is one of the most common causes of allergic contact dermatitis: a skin rash or irritation caused by touching an allergen. […] If you have a nickel allergy, the best way to avoid symptoms is to avoid objects containing nickel. […] Rashes caused by a nickel allergy are not life-threatening, but they can be uncomfortable.
  • #2 Systemic Nickel Allergy Syndrome (SNAS) – Research Article
    https://www.gavinpublishers.com/article/view/systemic-nickel-allergy-syndrome-taking-stock-of-medical-nutrition-therapy-snas-and-nutrition
    Many authors recommend the BraMaNi diet by Braga and Maccarinelli, developed to minimize additive content and vasoactive amines in foods. […] Adherence to a Nickel free diet is essential during the oral provocation test period to avoid false positive results. […] Nickel oral hyposensitization is a mechanism of immune tolerance in a Nickel-sensitized patient through the ingestion of low Nickel doses. […] According to preliminary results from the literature, a correlation between Nickel sensitive patients, gut microbiota composition, and obesity was identified. […] To date, data present in the literature related to this issue is still limited and controversial, and thus the role of gut microbiota related to SNAS patients must be further examined. […] At present, it is impossible to draw definite evidence-based recommendations about the nutritional support and management of SNAS. Nickel-free diets have been highly criticized for noncompliance and the inadequate intake of micronutrients.
  • #2 +Bioline International Official Site (site up-dated regularly)
    http://www.bioline.org.br/request?dv07116
    The degree and pattern of nickel allergy varies: Some patients develop vesicular type of hand eczema following the ingestion of nickel in diet. Such hand eczema flares up when such patients are treated with oral nickel sulfate. […] Studies have confirmed the role and benefit of hyposensitization with oral nickel in nickel allergy. It has been noted that oral tolerance to nickel sensitization can be obtained by feeding with nickel sulfate in nickel sensitive individual, and this has opened a new area of investigation for the treatment of nickel allergy. The suggested mechanism for oral hypo-sensitization in nickel-sensitive individual is the stimulation of the suppresser T-cell production by antigen excess. […] Nickel is a ubiquitous trace metal, and it is a fact that nickel cannot be completely avoided from diet; however, the careful selection of food with relatively low nickel concentration can bring a reduction in the total dietary intake of nickel per day. This can influence the outcome of nickel dermatitis. Studies have confirmed the benefit of low nickel diet in the management of nickel eczema.
  • #2 Relationship between nickel allergy and diet – Indian Journal of Dermatology, Venereology and Leprology
    https://ijdvl.com/relationship-between-nickel-allergy-and-diet/
    Nickel allergy is a chronic and recurring skin problem; females are affected more commonly than males. Nickel allergy may develop at any age. Once developed, it tends to persist life-long. Nickel in the diet of a nickel-sensitive person can provoke dermatitis. […] The degree and pattern of nickel allergy varies: (c) Some patients develop vesicular type of hand eczema following the ingestion of nickel in diet. […] Studies have confirmed the role and benefit of hyposensitization with oral nickel in nickel allergy. It has been noted that oral tolerance to nickel sensitization can be obtained by feeding with nickel sulfate in nickel sensitive individual, and this has opened a new area of investigation for the treatment of nickel allergy. The suggested mechanism for oral hypo-sensitization in nickel-sensitive individual is the stimulation of the suppresser T-cell production by antigen excess.
  • #2 Nickel Allergy and Autoimmune Disease
    https://www.verywellhealth.com/nickel-allergy-and-autoimmune-disease-5198646
    A nickel allergy could make you more susceptible to autoimmune disease, according to research. Nickel allergy is sometimes called nickel allergic contact dermatitis (NACD). […] Researchers are looking into common underlying mechanisms to understand how the two may be related. […] The precise relationship between these illnesses is unclear, but allergies and autoimmune diseases both involve similar immune-system activity. Several studies have noted a link between nickel allergies and autoimmune disease. […] A 2014 paper suggested that a systemic nickel allergy is a risk factor for developing autoimmune thyroid disease. Another study found that people with nickel allergy from oral exposure were especially likely to have an autoimmune disease. […] The International Academy of Oral Medicine and Toxicology (IOAMT) reported that metal can cause inflammation. And that inflammation can lead to the development of both allergic and autoimmune diseases.
  • #2 Irritable Bowel Syndrome and Nickel Allergy: What Is the Role of the Low Nickel Diet?
    https://www.jnmjournal.org/journal/view.html?doi=10.5056/jnm16027
    Irritable bowel syndrome (IBS) is characterized by chronic abdominal pain or discomfort accompanied by abnormal bowel movements. In sensitized subjects, ingested nickel (Ni) may induce gastrointestinal symptoms similar to IBS, in addition to typical systemic cutaneous lesions (systemic nickel allergy syndrome [SNAS]). A low nickel diet could improve the systemic manifestations. […] Growing evidence suggests that patients with IBS have decreased intestinal barrier function and that some forms of IBS are associated with low-grade intestinal inflammation. Similarly, Ni allergy is associated with immune system dysregulation with prevalent immunosuppressive action. In particular, Ni-sensitive patients with symptom recrudescence after Ni ingestion showed significant decrease of CD8+ and massive inflammatory infiltration of CD4+ CD45RO+ T lymphocytes in the duodenal lamina propria and epithelium as well as an involvement of Th2-type cytokines (IL-5 and IL-13).
  • #2 Semaphorin 3A: A potential target for prevention and treatment of nickel allergy | Communications Biology
    https://www.nature.com/articles/s42003-022-03641-0
    Metal allergy is one of the typical immune disorders encountered during the application of dental/medical materials and has a highly complex pathogenic mechanism. […] Herein, we show that Sema3A expression was upregulated in nickel (Ni) allergy-induced mouse ear tissue and in NiCl2-stimulated mouse keratinocytes. […] Our results demonstrate that Sema3A promotes the development of metal allergy and should be explored as a potential target for the prevention and treatment of metal allergy. […] We speculated that Sema3A, being a secretory protein, might function like cytokines or chemokines and may play a crucial role in both intercellular and intracellular communication, thereby influencing the process of metal allergy development. […] Sema3A may play a role in triggering or regulating the process of Ni allergy through p38 kinase activation and TNF- expression in keratinocytes.
  • #2 Immunological Mechanisms of Metal Allergies and the Nickel-Specific TCR-pMHC Interface
    https://www.mdpi.com/1660-4601/18/20/10867
    Cross-reactivity to different metal ions has been investigated in vivo by patch testing and in vitro by restimulation of metal-specific T cell clones. […] The wide variation in the frequencies of co-sensitized patients between different metal ions indicates that it is difficult to investigate the extent of T cell cross-reactivity by patch testing only. […] Cross-reactivity becomes likely with elements that are listed in close proximity in the PSE. Since Ni2+ and Pd2+ have physiochemical similarities, they can form similar complexes and thus trigger the same modifications in proteins present in the skin or pMHC.
  • #3 Nickel Allergy: Rash, Symptoms, Testing, Treatment & Prevention
    https://my.clevelandclinic.org/health/diseases/17842-nickel-allergy
    Nickel allergy is a skin rash or irritation that occurs when you come into contact with nickel. This condition is a form of allergic contact dermatitis. Allergic contact dermatitis happens when your skin touches or comes near an ordinarily harmless substance. Nickel allergy is the most common type of contact dermatitis related to metal. […] Researchers dont know the exact cause of nickel allergy. It happens when your immune system sees nickel as harmful. […] A nickel allergy may develop the first time youre exposed to nickel or after many times. Once your body has a first allergic reaction to nickel, youll likely continue to be allergic every time youre in contact with it.
  • #3 Allergic contact dermatitis: Immune system involvement and distinctive clinical cases | Allergologia et Immunopathologia
    https://www.elsevier.es/en-revista-allergologia-et-immunopathologia-105-articulo-allergic-contact-dermatitis-immune-system-S030105461100200X
    Chemically reactive small molecular compounds penetrating into the skin may determine a hapten-specific immune response that involves T cells, invariant Natural Killer T cells, Natural Killer, T regulatory cells, epidermal Langerhans cells and keratinocytes. […] Two temporally and spatially spaced phases are usually necessary to achieve a contact hypersensitivity reaction: the sensitisation and the elicitation phase. […] In the sensitisation phase, which occurs at the first contact of the skin with the hapten, the innate immunity induces inflammation and consequently the recruitment of dendritic cells, especially Langerhans cells, and leukocytes. […] Re-exposure of sensitised individuals with the same hapten induces the activation of specific T lymphocytes in the dermis and the epidermis and triggers the inflammatory process responsible for the appearance of cutaneous lesions within 24/72h.
  • #3 A Novel DC Therapy with Manipulation of MKK6 Gene on Nickel Allergy in Mice | PLOS One
    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0019017
    Although the activation of dermal dendritic cells (DCs) or Langerhans cells (LCs) via p38 mitogen-activated protein kinase (MAPK) plays a crucial role in the pathogenesis of metal allergy, the in vivo molecular mechanisms have not been identified and a possible therapeutic strategy using the control of dermal DCs or LCs has not been established. […] The activation of dermal DCs via p38 MAPK triggered a T cell-mediated allergic immune response in this model. In the MAPK signaling cascade in DCs, Ni potently phosphorylated MAP kinase kinase 6 (MKK6) following increased DC activation. […] The cooperative action between T cell activation and MKK6-mediated DC activation by Ni played an important role in the development of Ni allergy. […] DC activation by Ni played an important role in the development of Ni allergy. Manipulating the MKK6 gene in DCs may be a good therapeutic strategy for dermal Ni allergy.
  • #3 Systemic Nickel Allergy Syndrome (SNAS) – Research Article
    https://www.gavinpublishers.com/article/view/systemic-nickel-allergy-syndrome-taking-stock-of-medical-nutrition-therapy-snas-and-nutrition
    Systemic Nickel Allergy Syndrome (SNAS) manifestation is instead characterized by gastrointestinal symptoms including bloating, diarrhea or constipation, vomiting, nausea, abdominal pain, and cutaneous signs. […] It is well documented that Nickel is a strong hapten with a good chemical reactivity and a high molecular weight and hydrophobicity, which facilitates its penetration through the skin and mucous membranes. Nickel combines with some skin proteins of the skin and establishes an antigenic complex, which is recognized as non-self by the immune system triggering an immune response. […] In the specific case of SNAS, dietary Nickel ingestion causes Nickel conjugation to intestinal proteins. Nickel’s ability to induce an allergic reaction is due to the presence of two unpaired electrons in its peripheral orbit, which allow an organic bond with peptides or proteins leading to antigenic complexes responsible for allergic reactions.
  • #3 Azthena logo with the word Azthena
    https://www.news-medical.net/health/Nickel-Allergy.aspx
    Nickel ingestion through the diet in nickel-sensitive people triggers a series of changes in the immune system that can lead to the development of clinical reactions. […] Nickel ingestion causes a decrease in circulating CD8+, CD45RO+, and CLA+ blood lymphocytes, which can lead to the migration of CD8+ memory T cells into the tissues. […] Dietary ingestion of nickel also increases interleukin (IL)-5 levels in the serum. As a result, there is a rapid increase in the reproduction of eosinophils, which are white bloods cells that help fight allergies and infections. […] The mechanism of absorption of ingested nickel in the body is not fully understood yet, though it has been proved that vitamin C and iron are capable of decreasing the absorption of dietary nickel. Therefore, iron-rich foods and vitamin C supplements can help reduce the amount of nickel absorbed by the body.
  • #3 Nickel Allergy – ECARF
    https://www.ecarf.org/en/information-portal/allergies-overview/nickel-allergy/
    A patch test is used to diagnose a contact allergy. For this test, adhesive tape with test chambers is applied onto the skin, usually on the back. The test chambers contain allergens and, if necessary, other suspected substances. The test results are read after 48 and 72 hours. […] The most effective method for relieving symptoms is to avoid the allergy-triggering substance. People who are allergic to nickel should stay away from everyday objects containing nickel and avoid prolonged skin contact. If contact cannot be avoided completely, safety measures such as gloves or protective clothing can help. […] In rare cases, the nickel content in food can exacerbate eczema in patients with a severe nickel allergy.
  • #3 Relationship between nickel allergy and diet – Indian Journal of Dermatology, Venereology and Leprology
    https://ijdvl.com/relationship-between-nickel-allergy-and-diet/
    Nickel allergy is a chronic and recurring skin problem; females are affected more commonly than males. Nickel allergy may develop at any age. Once developed, it tends to persist life-long. Nickel in the diet of a nickel-sensitive person can provoke dermatitis. […] The degree and pattern of nickel allergy varies: (c) Some patients develop vesicular type of hand eczema following the ingestion of nickel in diet. […] Studies have confirmed the role and benefit of hyposensitization with oral nickel in nickel allergy. It has been noted that oral tolerance to nickel sensitization can be obtained by feeding with nickel sulfate in nickel sensitive individual, and this has opened a new area of investigation for the treatment of nickel allergy. The suggested mechanism for oral hypo-sensitization in nickel-sensitive individual is the stimulation of the suppresser T-cell production by antigen excess.
  • #3 +Bioline International Official Site (site up-dated regularly)
    http://www.bioline.org.br/request?dv07116
    The degree and pattern of nickel allergy varies: Some patients develop vesicular type of hand eczema following the ingestion of nickel in diet. Such hand eczema flares up when such patients are treated with oral nickel sulfate. […] Studies have confirmed the role and benefit of hyposensitization with oral nickel in nickel allergy. It has been noted that oral tolerance to nickel sensitization can be obtained by feeding with nickel sulfate in nickel sensitive individual, and this has opened a new area of investigation for the treatment of nickel allergy. The suggested mechanism for oral hypo-sensitization in nickel-sensitive individual is the stimulation of the suppresser T-cell production by antigen excess. […] Nickel is a ubiquitous trace metal, and it is a fact that nickel cannot be completely avoided from diet; however, the careful selection of food with relatively low nickel concentration can bring a reduction in the total dietary intake of nickel per day. This can influence the outcome of nickel dermatitis. Studies have confirmed the benefit of low nickel diet in the management of nickel eczema.
  • #3 Nickel Allergy and Autoimmune Disease
    https://www.verywellhealth.com/nickel-allergy-and-autoimmune-disease-5198646
    A nickel allergy could make you more susceptible to autoimmune disease, according to research. Nickel allergy is sometimes called nickel allergic contact dermatitis (NACD). […] Researchers are looking into common underlying mechanisms to understand how the two may be related. […] The precise relationship between these illnesses is unclear, but allergies and autoimmune diseases both involve similar immune-system activity. Several studies have noted a link between nickel allergies and autoimmune disease. […] A 2014 paper suggested that a systemic nickel allergy is a risk factor for developing autoimmune thyroid disease. Another study found that people with nickel allergy from oral exposure were especially likely to have an autoimmune disease. […] The International Academy of Oral Medicine and Toxicology (IOAMT) reported that metal can cause inflammation. And that inflammation can lead to the development of both allergic and autoimmune diseases.
  • #3 Irritable Bowel Syndrome and Nickel Allergy: What Is the Role of the Low Nickel Diet?
    https://www.jnmjournal.org/journal/view.html?doi=10.5056/jnm16027
    Irritable bowel syndrome (IBS) is characterized by chronic abdominal pain or discomfort accompanied by abnormal bowel movements. In sensitized subjects, ingested nickel (Ni) may induce gastrointestinal symptoms similar to IBS, in addition to typical systemic cutaneous lesions (systemic nickel allergy syndrome [SNAS]). A low nickel diet could improve the systemic manifestations. […] Growing evidence suggests that patients with IBS have decreased intestinal barrier function and that some forms of IBS are associated with low-grade intestinal inflammation. Similarly, Ni allergy is associated with immune system dysregulation with prevalent immunosuppressive action. In particular, Ni-sensitive patients with symptom recrudescence after Ni ingestion showed significant decrease of CD8+ and massive inflammatory infiltration of CD4+ CD45RO+ T lymphocytes in the duodenal lamina propria and epithelium as well as an involvement of Th2-type cytokines (IL-5 and IL-13).
  • #3 Semaphorin 3A: A potential target for prevention and treatment of nickel allergy | Communications Biology
    https://www.nature.com/articles/s42003-022-03641-0
    Metal allergy is one of the typical immune disorders encountered during the application of dental/medical materials and has a highly complex pathogenic mechanism. […] Herein, we show that Sema3A expression was upregulated in nickel (Ni) allergy-induced mouse ear tissue and in NiCl2-stimulated mouse keratinocytes. […] Our results demonstrate that Sema3A promotes the development of metal allergy and should be explored as a potential target for the prevention and treatment of metal allergy. […] We speculated that Sema3A, being a secretory protein, might function like cytokines or chemokines and may play a crucial role in both intercellular and intracellular communication, thereby influencing the process of metal allergy development. […] Sema3A may play a role in triggering or regulating the process of Ni allergy through p38 kinase activation and TNF- expression in keratinocytes.
  • #3 Systemic Nickel Allergy Syndrome (SNAS) – Research Article
    https://www.gavinpublishers.com/article/view/systemic-nickel-allergy-syndrome-taking-stock-of-medical-nutrition-therapy-snas-and-nutrition
    Many authors recommend the BraMaNi diet by Braga and Maccarinelli, developed to minimize additive content and vasoactive amines in foods. […] Adherence to a Nickel free diet is essential during the oral provocation test period to avoid false positive results. […] Nickel oral hyposensitization is a mechanism of immune tolerance in a Nickel-sensitized patient through the ingestion of low Nickel doses. […] According to preliminary results from the literature, a correlation between Nickel sensitive patients, gut microbiota composition, and obesity was identified. […] To date, data present in the literature related to this issue is still limited and controversial, and thus the role of gut microbiota related to SNAS patients must be further examined. […] At present, it is impossible to draw definite evidence-based recommendations about the nutritional support and management of SNAS. Nickel-free diets have been highly criticized for noncompliance and the inadequate intake of micronutrients.
  • #4 A Novel DC Therapy with Manipulation of MKK6 Gene on Nickel Allergy in Mice | PLOS One
    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0019017
    p38 MAPK is activated by an upstream kinase (MKK6 or MKK3) and then translocated into the nucleus where target molecules are phosphorylated by p38 MAPK. […] Our experiments using a Ni allergy model strongly suggest that MKK6 phosphorylation in dermal DCs is the first important trigger for the onset of an allergic response to Ni. […] Our in vivo experiments demonstrated that manipulating the MKK6 gene of DCs could control Ni allergy.
  • #4 Nickel Allergy – ECARF
    https://www.ecarf.org/en/information-portal/allergies-overview/nickel-allergy/
    A patch test is used to diagnose a contact allergy. For this test, adhesive tape with test chambers is applied onto the skin, usually on the back. The test chambers contain allergens and, if necessary, other suspected substances. The test results are read after 48 and 72 hours. […] The most effective method for relieving symptoms is to avoid the allergy-triggering substance. People who are allergic to nickel should stay away from everyday objects containing nickel and avoid prolonged skin contact. If contact cannot be avoided completely, safety measures such as gloves or protective clothing can help. […] In rare cases, the nickel content in food can exacerbate eczema in patients with a severe nickel allergy.
  • #4 Nickel Allergy and Autoimmune Disease
    https://www.verywellhealth.com/nickel-allergy-and-autoimmune-disease-5198646
    A nickel allergy could make you more susceptible to autoimmune disease, according to research. Nickel allergy is sometimes called nickel allergic contact dermatitis (NACD). […] Researchers are looking into common underlying mechanisms to understand how the two may be related. […] The precise relationship between these illnesses is unclear, but allergies and autoimmune diseases both involve similar immune-system activity. Several studies have noted a link between nickel allergies and autoimmune disease. […] A 2014 paper suggested that a systemic nickel allergy is a risk factor for developing autoimmune thyroid disease. Another study found that people with nickel allergy from oral exposure were especially likely to have an autoimmune disease. […] The International Academy of Oral Medicine and Toxicology (IOAMT) reported that metal can cause inflammation. And that inflammation can lead to the development of both allergic and autoimmune diseases.
  • #5 Nickel Allergy – ECARF
    https://www.ecarf.org/en/information-portal/allergies-overview/nickel-allergy/
    A patch test is used to diagnose a contact allergy. For this test, adhesive tape with test chambers is applied onto the skin, usually on the back. The test chambers contain allergens and, if necessary, other suspected substances. The test results are read after 48 and 72 hours. […] The most effective method for relieving symptoms is to avoid the allergy-triggering substance. People who are allergic to nickel should stay away from everyday objects containing nickel and avoid prolonged skin contact. If contact cannot be avoided completely, safety measures such as gloves or protective clothing can help. […] In rare cases, the nickel content in food can exacerbate eczema in patients with a severe nickel allergy.
  • #5 Nickel Allergy and Autoimmune Disease
    https://www.verywellhealth.com/nickel-allergy-and-autoimmune-disease-5198646
    A nickel allergy could make you more susceptible to autoimmune disease, according to research. Nickel allergy is sometimes called nickel allergic contact dermatitis (NACD). […] Researchers are looking into common underlying mechanisms to understand how the two may be related. […] The precise relationship between these illnesses is unclear, but allergies and autoimmune diseases both involve similar immune-system activity. Several studies have noted a link between nickel allergies and autoimmune disease. […] A 2014 paper suggested that a systemic nickel allergy is a risk factor for developing autoimmune thyroid disease. Another study found that people with nickel allergy from oral exposure were especially likely to have an autoimmune disease. […] The International Academy of Oral Medicine and Toxicology (IOAMT) reported that metal can cause inflammation. And that inflammation can lead to the development of both allergic and autoimmune diseases.

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mutacja filagryny test płatkowy nadwrażliwość typu IV autoimmunologiczna choroba tarczycy kinaza białkowa aktywowana mitogenami objawy żołądkowo-jelitowe prezentacja antygenu dieta niskonieklowa limfocyt CD8 receptor Toll-podobny 4 semaforyna 3A kortykosteroid ogólnoustrojowy mikrobiom jelitowy alergiczne kontaktowe zapalenie skóry zespół jelita drażliwego reaktywność krzyżowa faza wywołania choroba autoimmunologiczna terapia PUVA cytokina prozapalna komórka Langerhansa faza sensytyzacji limfocyt CD4+ systemowa alergia na nikiel cyklosporyna limfocyt T