1. Kounis Syndrome
and Intracardiac
Metal Devices
From Bedside to Bench!
“A hypersensitivity blow up inside the heart”
Nicholas Kounis, Iatros, MD, FESC, FACC

3. Hypersensitivity inflammation
+
Acute coronary syndrome

4. Hypersensitivity inflammation
+
Acute coronary syndrome
Hypersensitivity coronary syndrome
(Kounis syndrome)

5. Hypersensitivity inflammation
Acute coronary syndrome
Hypersensitivity coronary syndrome
(Kounis syndrome)

6. Intracardiac devices Containing
Nickel and Other Metals
2. Devices for Closure
1. Coronary Stents Of Atrial
Septal Defects
including Bare and Patent Foramen
Metal Stents Ovale
(BMS) and Drug
Eluting Stents 3.Cardiac
Pacemakers and
(DES)
defibrillators
4. Artificial Cardiac
Valves

7. Kounis syndrome: the
hypersensitivity coronary syndrome
What is?
“The concurrence of acute coronary syndromes with conditions
associated with mast cell activation, involving interrelated and
interacting inflammatory cells, and including allergic or
hypersensitivity and anaphylactic or anaphylactoid insults”. “It is
caused by inflammatory mediators such as histamine, neutral
proteases, arachidonic acid products, platelet activating factor
and a variety of cytokines and chemokines released during the
activation process.” “A subset of platelets bearing FCεRI and
FCεRII receptors are also involved in the activation cascade”
Mast cells
Macrophages T-cells
Mast cells

8. The vicious cycle of
inflammatory cells
All these inflammatory cells participate in a
Macrophages vicious inflammatory cycle and via
multidirectional signals:
1. Mast cells can enhance T cell
activation1
Mast cells 2. T cells can mediate mast cell activation
and proliferation2
Macrophages
3. Inducible macrophage protein-1α can
activate mast cells3
4. mast cells can activate macrophages4
T-cells 5. T cells can regulate macrophage
activity5
Macrophages 1. Nakae S, et al. J Immunol 2006; 176: 2238
2. Mecori YA, et al. Clin Immunol 1999; 104: 517
3. Miyazaki D, et al. J Clin Invest 2005; 115: 434
4. Salari H, et al. J Immunol 1989; 142: 2821
5. Doherty TM. Curr Opin Immunol 1995; 7: 400

9. Kounis syndrome variants
Type I variant: includes patients with normal
coronary arteries without predisposing factors for coronary artery
disease in whom the acute release of inflammatory mediators can
induce either coronary artery spasm without increase of cardiac
enzymes and troponins or coronary artery spasm progressing to
acute myocardial infarction with raised cardiac enzymes and
troponin Nikolaidis LA, et al. Can J Cardiol 2002; 18: 508
Type II variant: includes patients with culprit but
quiescent pre-existing atheromatous disease in whom the acute
release of inflammatory mediators can induce either coronary artery
spasm with normal cardiac enzymes and troponins or plaque
erosion or rupture manifesting as acute myocardial infarction
Nikolaidis LA, et al. Can J Cardiol 2002; 18: 508
Type III variant: includes patients with coronary
artery stent thrombosis in whom aspirated thrombus specimens
stained with hematoxylin-eosin and Giemsa demonstrate the
presence of eosinophils and mast cells respectively
Biteker M. Expert Rev Clin Immunol 2010; 6: 777-88

10. Kounis syndrome:
main actions of main mediators
Cardiac effects of histamine
1.Coronary vasoconstriction (histamine test)
2. Induces tissue factor expression and activity
3. Activates platelets and potentiates the
aggregatory response of agonists e.g.
adrenaline, 5-hydroxytryptamine, and thrombin
4. Intimal thickening
5. Inflammatory cell modulation
6. Modulates the activity of neutrophils,
monocytes, and eosinophils
7. Proinflammatory cytokine production
8. P-selectine upregulation
9. Sensitizites nerve endings in coronary plaques

11. Kounis syndrome: cardiac actions of
main mediators: Proteases
Tryptase Chymase
1. Activates the zymogen forms of 1. Converts angiotensin I to
metalloproteinases such as angiotensin II and angiotensin II
interstitial collagenase, gelatinase, receptors are found in the medial
and stromelysin and can promote muscle cells of human coronary
plaque disruption or rupture. arteries. Thus, angiotensin II
2. Degrates the pericellular matrix generated by chymase could act
components fibronectin and synergistically with histamine and
vitronectin and neuropeptides, aggravate the local spasm of the
such as vasoactive intestinal infarcted coronary artery. Chymase
peptide (VIP) and calcitonin gene also can remove cholesterol from
related peptide (CGRP) HDL
3. Tryptase can degrade HDL 2. Activates MMP-1,-2,-9 and plays a
4. Activates neighboring cells by major role in the physiologic
cleaving and activating protease- degradation of fibronectin and
activated receptor (PAR)-2, and thrombin
thrombin receptors 3. Releases latent TGF-β1 from the
extracellular matrix
4. Inhibits smooth muscle growth
Cathepsin D 5. Induces apoptosis of arterial smooth
1. Angiotensin II-forming protease muscle cells and endothelial cells
2.Degrates both fibronectin and VE-cadherin which are
necessary for adhesion of endothelial cells to their basement
membrane and to each other

12. Kounis syndrome: cardiac actions
of the main mediators
Leukotrienes: Powerful arterial vasoconstrictors
and their biosynthesis is enhanced in the acute phase of
unstable angina
Thromboxane: A potent mediator of platelet
aggregation with vasoconstricting properties
Platelet activating factor: In myocardial
ischemia acts as proadhesive signalling molecule or via
activation of leucocytes and platelets to release other
mediators. In experimental anaphylaxis reproduces the
electrical and mechanical effects observed in allergic
reactions such as ST changes and arrhythmias acting
either through the release of leukotrienes or as a direct
vasoconstrictor

13. How Kounis syndrome is associated with stent and other
devices thrombosis? Antigens are necessary and antigens are
present not only throughout stenting process but
also after implantation of devices containing nickel,
polymers and other metals
the Facts
the evidence
the mechanism

14. 3
THE FACTS: First generation Drug
Eluting Stents components:
1.The metal itself is made from
stainless steel which contains:
nickel, chromium, manganese, titanium and molybdenum
2.The polymer coating
3.The antineoplastic Paclitaxel
3.The antiproliferative Rapamycin
All these are strong allergens and
constitute the “stent antigenic complex”
Kounis NG, et al. J Am Coll Cardiol 2006; 48: 592

15. Hypersensitivity to Drug Eluting
Stents components and Kounis
syndrome
Hypersensitivity reactions to nickel
allergic contact dermatitis
baboon syndrome (erythema in the buttocks and upper
inner thighs resembling the red bottom of baboons)
bronchial asthma
dependent edema
diffuse exanthema
fever
flexural dermatitis
itching erythema
pericarditis
pompholyx formation
rosacea
sarcoid granuloma (delayed hypersensitivity)
Kounis NG. Hahalis G, Theoharides TC. J Interven Cardiol 2007; 20: 314

16. Hypersensitivity to Drug Eluting
stents components and Kounis
syndrome
Hypersensitivity reactions with the use of polymers
and Latex
-allergic conjunctivitis
-allergic rhinitis
-allergic allergic stomatitis
-facial angioedema
-generalized anaphylactic reaction
-generalized urticaria
-interstitial asthma
-neurodermatitis
-stomatitis venenada
Kounis NG. Hahalis G, Theoharides TC. J Interven Cardiol 2007; 20: 314

17. Hypersensitivity to Drug Eluting
Stents components and Kounis
syndrome
Hypersensitivity reactions with the use of paclitaxel
-angioedema
-atrioventricular block
-bronchospasm
-cutaneous flushing
-diaphoresis
-Kounis syndrome
-left bundle branch block
-ventricular tachycardia
-urticaria
Kounis NG. Hahalis G, Theoharides TC. J Interven Cardiol 2007; 20: 314

18. Hypersensitivity to Drug Eluting
Stents components and Kounis
syndrome
Hypersensitivity reactions of Rapamycin
-acrocyanosis
-angioedema
-flushing
-pruritus
-interstitial pneumonitis
-Schonlein-Henoch purpura
-localized eczematiform eruption
-palpable purpura due to leucocytoplastic vasculitis
-paradoxic coronary vasoconstriction
Kounis NG. Hahalis G, Theoharides TC. J Interven Cardiol 2007; 20: 314

19. SECOND GENERATION STENTS:
they are named cobalt-chromium
stents (misleading term?)
Xience
(everolimus) stent
The information we have obtained from
the manufacturer indicates that the alloy
composition of the Xience stent is 55%
cobalt 20% chromium, 15% tungsten,
10% nickel
Min. Max
Carbon 0.05 0.15
Manganese 1.00 2.00
Silicon -- 0.40
Phosphorus -- 0.040
Sulfur -- 0.030
Chromium 19.00 21.00
Nickel 9.00 11.00
Tungsten 14.00 16.00
ron -- 3.00
Cobalt* Balance Balance
•

20. SECOND GENERATION STENTS:
they are named cobalt-chromium
stents (misleading term?)
Xience Endeavor
(everolimus) stent (zotarolimus) stent
The information we have obtained from
the manufacturer indicates that the alloy
composition of the Xience stent is 55%
cobalt 20% chromium, 15% tungsten,
10% nickel
Min. Max
Carbon 0.05 0.15
Manganese 1.00 2.00
Silicon -- 0.40
Phosphorus -- 0.040
Sulfur -- 0.030
Chromium 19.00 21.00
Nickel 9.00 11.00
Tungsten 14.00 16.00
ron -- 3.00
Cobalt* Balance Balance
•

21. 4. Clopidogrel-induced allergic
skin rash

22. 4. Clopidogrel-induced allergic
skin rash
5. Kounis NG, et al. “Myocardial
infarction after aspirin treatment,
and the Kounis syndrome”. J R Soc
Med 2005; 98: 296

23. 6. Atopic stented individuals are
under the risk of any additional
drug or environmental
exposure which may “join
forces” with the previous 5
agents and trigger the cascade
of intrastent thrombosis

24. More than 5 antigens are irreversibly implanted
and some of them apply continuous, persistent,
chronic and repetitive allergic irritation!
Allergic inflammation is initiated by allergens
cross-bridging their corresponding, receptor-
bound, immunoglobin IgE or IgG antibodies on “ IgE antibodies with different
the surface of the mast cells or basophils. A
total of 1000 bridges are necessary to trigger
specificities can have an
the cell out of maximal number of some 500 000 additive effect i.e. if mast cells
-1 000 000 IgE molecules on the cell surface. It are sensitized with small, even
might be possible to accumulate the critical
number of bridges by more than one noncross- subthreshold numbers of IgE
reactive allergen and its corresponding IgE
antibody
antibodies of different
specificities they can “join
forces” and trigger the cells to
release its mediators,if the
patient is simultaneously
exposed to corresponding
allergens”
Nopp A, et al. Allergy 2006; 61: 1336
MacGlashan DW, et al. J Immunol 1997; 158: 1438

25. Stents, like magnet, attract
inflammatory cells!
1. Stent thrombosis associated with allergic symptoms such
as glottis edema, cold sweat, and tongue enlargement
followed a flavonate-propyphenasone administration a week
after stent implantation. Int J Cardiol. 2009; 134: e45-6.
2. Acute myocardial infarction, in the stented area, coincided
with allergic reaction following intravenous administration of
the non-anionic contrast material iopromide during a routine
excretory urography . Int J Cardiol 2010; 139: 206-9.
3. Intrastent thromboses have also been reported following
insect and larvae sting allergic reactions. Cases J. 2009; 2: 7800

26. Types of PFO and ASD ocluders containing
nitinol ( nickel-titanium alloy)
AMPLATZER® device - used for PFO repair GORE HELEX Septal Occluder - used for PFO
repair

28. The generators are covered with titanium and the
pacing leads are made from MP35N (an alloy of
Ni, Co, Cr, and Mo)

29. Artificial heart valves: Parts are
made of Co-Cr-W-Ni alloy. Today
nickel free-valves are available

30. The ASD and PFO closure device and
Kounis syndrome symptoms and signs
The “Device syndrome”
Eight out of 9 patients with proven,
by skin tests, allergy to nickel
developed a syndrome the 2nd and
3rd posroperative day after
implantation a full nitinol Aplatzer
occluder and low nitinol Premere
closure system consisting of:
-exertional dyspnea
-palpitations
-worsening of headache
-asthenia
-leukocytosis
-atrial fibrillation (2 patients with
negative skin patch testing but
with occluder system implantation)
Rigatelli G, et al. Congenit Heart Dis 2007;2:416–20

31. The ASD and PFO closure device and
Kounis syndrome symptoms and signs
The “Device syndrome” The Kounis syndrome
Eight out of 9 patients with proven,
by skin tests, allergy to nickel • -Chest discomfort
developed a syndrome the 2nd and • -Acute chest pain
3rd posroperative day after • -Dyspnea
implantation a full nitinol Aplatzer • -Faintness
occluder and low nitinol Premere • -Nausea
• -Vomiting
closure system consisting of: • -Syncope
-exertional dyspnea • -Pruritus
-palpitations • -Urticaria
-worsening of headache • -Hypotention
-asthenia • -Diaphoresis
-leukocytosis • -Pallor
• -Palpitations
-atrial fibrillation (2 patients with • -Bradycardia
negative skin patch testing but • -Tachycardia
with occluder system implantation) Kounis NG, et al. Br J Clin Pract 1991;45:121–8
Rigatelli G, et al. Congenit Heart Dis 2007;2:416–20

32. Kounis syndrome and intracardiac Devices
THE EVIDENCE

33. -Localized Hypersensitivity and Late Coronary
Thrombosis Secondary to a Sirolimus-Eluting Stent
Should We Be Cautious?-
Virmani et al. Circulation 2004; 109: 701
Focal strut malapposition
with aneurysmal dilatation
(double arrows in D and F)
and occlusive luminal
thrombosis
E Extensive inflammation
consisting primarily of
eosinophils and
lymphocytes, with a focal
giant cell reaction around
stent strut (*) and
surrounding polymer.
Marked inflammation is
similarly present in intima,
media, and adventitia in J
(left box in E). K and L
(Luna stains) show giant
cells (arrowheads) around
a polymer remnant that
has separated from stent
numerous
strut and
eosinophils
within arterial
wall

34. It has been stated that
“eosinophilic infiltration
of intrastent thrombus
seems to be a common
finding in stented
patients and is not a
peculiarity”
Zavalloni D, et al. J Cardiovasc Med 2009;10: 942

35. Kounis syndrome and intracardiac device
thrombosis
THE MECHANISM

36. Platelets play a central role in pathogenesis of thrombosis

37. Stent thrombosis
1. Platelet adhesion
2. Platelet activation
3. Platellet aggregation

38. LMW Heparin
2.
PATHOPHYSIOLOGY OF STENT THROMBOSIS AND KOUNIS SYNDROME
Mast cell HIRUDIN
Mast cell BIVALIRUDIN
Eosinophil Triflusal
Aspirin
Ticagrelor TXA2
Clopidogrel
Prasugrell thrombin
Ticlopidin
ADP
(P2Y12)
2. ACTIVATION
GP IIb/ IIIa receptors serotonin
serotonin
Pl changes from discoid
to spiculated form
Fibrinogen
Degranulation
epinephrine
Mediators
GP IIb/ IIIa inhibitors Adhesive (vWF, fibrinogen) ME
1. ADHESION Prothrombotic (V,XI, PAI-1) DA
Proinflammatory (PDGF, PF4)
Via interaction of Aggregatory (ADP, ATP, Ca, Mg) TO
3. AGGREGATION
GP IIb/II/a and vWF RS

39. LMW Heparin
2.
PATHOPHYSIOLOGY OF STENT THROMBOSIS AND KOUNIS SYNDROME
Mast cell HIRUDIN
Mast cell BIVALIRUDIN
Eosinophil Triflusal
Aspirin PAF
Ticagrelor TXA2
Clopidogrel
Prasugrell thrombin
Ticlopidin
ADP
(P2Y12)
2. ACTIVATION
GP IIb/ IIIa receptors serotonin
serotonin
Pl changes from discoid
to spiculated form
Fibrinogen
Degranulation
epinephrine
Mediators
GP IIb/ IIIa inhibitors Adhesive (vWF, fibrinogen) ME
1. ADHESION Prothrombotic (V,XI, PAI-1) DA
Proinflammatory (PDGF, PF4)
Via interaction of Aggregatory (ADP, ATP, Ca, Mg) TO
3. AGGREGATION
GP IIb/II/a and vWF RS

40. PATHOPHYSIOLOGY OF STENT THROMBOSIS AND KOUNIS SYNDROME LMW Heparin
2. Mast cell
Mast cell
HIRUDIN
BIVALIRUDIN
Eosinophil Triflusal
Aspirin PAF histamine
Ticagrelor TXA2
Clopidogrel
Prasugrell thrombin
Ticlopidin
ADP
(P2Y12)
2. ACTIVATION
GP IIb/ IIIa receptors serotonin
serotonin
Pl changes from discoid
to spiculated form
Fibrinogen
Degranulation
epinephrine
Mediators
GP IIb/ IIIa inhibitors Adhesive (vWF, fibrinogen) ME
1. ADHESION Prothrombotic (V,XI, PAI-1) DA
Proinflammatory (PDGF, PF4)
Via interaction of Aggregatory (ADP, ATP, Ca, Mg) TO
3. AGGREGATION
GP IIb/II/a and vWF RS

41. PATHOPHYSIOLOGY OF STENT THROMBOSIS AND KOUNIS SYNDROME LMW Heparin
2. Mast cell
Mast cell
HIRUDIN
BIVALIRUDIN
Eosinophil Triflusal
Aspirin PAF histamine
FCεRI-FCεRII
Ticagrelor TXA2
Clopidogrel
Prasugrell thrombin
Ticlopidin
ADP
(P2Y12)
2. ACTIVATION
GP IIb/ IIIa receptors serotonin
serotonin
Pl change from discoid
to spiculated form
Fibrinogen
Degranulation
epinephrine
Mediators
GP IIb/ IIIa inhibitors Adhesive (vWF, fibrinogen) ME
1. ADHESION Prothrombotic (V,XI, PAI-1) DA
Proinflammatory (PDGF, PF4)
Via interaction of Aggregatory (ADP, ATP, Ca, Mg) TO
3. AGGREGATION
GP IIb/II/a and vWF RS

42. PATHOPHYSIOLOGY OF STENT THROMBOSIS AND KOUNIS SYNDROME LMW Heparin
Mast cell HIRUDIN
MAST CELL INHIBITORS
Mast cell BIVALIRUDIN
Eosinophil Triflusal
Aspirin PAF histamine
FCεRI-FCεRII
Ticagrelor TXA2
Clopidogrel
Prasugrell thrombin
Ticlopidin
ADP
(P2Y12)
2. ACTIVATION
GP IIb/ IIIa receptors serotonin
serotonin
Pl changes from discoid
to spiculated form
Fibrinogen
Degranulation
epinephrine
Mediators
GP IIb/ IIIa inhibitors Adhesive (vWF, fibrinogen) ME
1. ADHESION Prothrombotic (V,XI, PAI-1) DA
Proinflammatory (PDGF, PF4)
Via interaction of Aggregatory (ADP, ATP, Ca, Mg) TO
3. AGGREGATION
GP IIb/II/a and vWF RS

44. Petrikova M, et al. H1 antihistamines and
activated blood platelets. Inflammation
Res 2006; 55 Suppl 1: S51-S52.
Antihistamines Dithiaden, Loratadine and Bromadyl
inhibited platelet activation-aggregation in 3
experimental systems:
1. Whole human blood from healthy male donors
2. Platelets in plasma
3. Isolated platelets
Despite their stimulation with
adenosine-5`-diphosphate (ADP)
It was thought that this action was on cytosolic
phospholipase A2 at arachidonate cascade rather than at
specific histamine receptors (!)

45. In patients with cardiac pacemakers and defibrillators who
died: Thrombi were found at autopsy in 33% of ventricular
and 48% on atrial leads
Novak M, et al. Europace. 2009; 11: 1510-6

47. Thrombus after ASD and PFO
Device closure Krumsdorf U, et al. JACC 2004;43; 302-9

48. Mid esophageal 2 (chamber view, 90 degrees).
95-1596
Cardona L et al. Circulation 2011;124:1595-1596

49. Prevention of
thrombosis

50. Fighting against stent thrombosis
1.Taking careful history of
adverse drug reactions and
allergies
2.Monitoring of inflammatory
mediators after stent or
device insertion
3.Performing antibody and skin
testing when and where
appropriate
4.Performing macrophage and
T-cell activation studies
5.Considering desensitization
strategies
6.Considering the use of mast
cell stabilizers and steroids
Kounis NG, et al. J Am Coll Cardiol 2006; 48: 592
Kounis NG, et al N Engl J Med 2006; 354: 2076
7.Measuring of acute phase reactans
8.Periprocedural antiinflammatory therapy
Gaspardone A, Versaci F. Am J Med 2005; 96: 65L

51. Fighting against stent thrombosis
1.Taking careful history of
adverse drug reactions and
allergies
2.Monitoring of inflammatory
mediators after stent or
device insertion
3.Performing antibody and skin
testing when and where
appropriate
4.Performing macrophage and
T-cell activation studies
5.Considering desensitization
strategies
6.Considering the use of mast
cell stabilizers and steroids
Kounis NG, et al. J Am Coll Cardiol 2006; 48: 592
Kounis NG, et al N Engl J Med 2006; 354: 2076
7.Measuring of acute phase reactans
8.Periprocedural antiinflammatory therapy
Gaspardone A, Versaci F. Am J Med 2005; 96: 65L

52. Fighting against stent thrombosis
1.Taking careful history of
adverse drug reactions and
allergies
2.Monitoring of inflammatory
mediators after stent or
device insertion
3.Performing antibody and skin
testing when and where
appropriate
4.Performing macrophage and
T-cell activation studies
Which means that allergic
5.Considering desensitization
strategies predisposition
6.Considering the use of mast may help in prediction of
cell stabilizers and steroids the risk for stent
Kounis NG, et al. J Am Coll Cardiol 2006; 48: 592
Kounis NG, et al N Engl J Med 2006; 354: 2076
thrombosis
7.Measuring of acute phase reactans
8.Periprocedural antiinflammatory therapy
Gaspardone A, Versaci F. Am J Med 2005; 96: 65L

53. Future
directions for
stents and other
devices

54. 1.Nickel free stainless steel with number
of blood platelets attached to and 316L stainless steel
after dipping in fresh human blood plasma for
25 min and 3 hours
Yang K, Ren Y. Sci Technol Adv Mater
2010; 11: 1-13

55. Nickel sensitization (patch test)in North-Eastern Italy
(Belluno, Bolzano, Padova, Pordedone,
Rovereto,Rovigo, Trento, Trieste)
31.6% in women (9771)
10.0% in men (4693)
The overall prevalence 24.6%

56. Bioabsorbable Stents
• …At 2 years after
implantation the
stent was
bioabsorbed, had
vasomotion
restored, restenosis
prevented and was
clinically safe,
suggesting freedom
from late thrombosis
Serruys PW, et al. Lancet; 2009; 373: 897

57. Bioabsorbable Stents
• …At 2 years after
implantation the • ..However, three
stent was “mores” are
bioabsorbed, had needed: more
vasomotion patients, more
restored, restenosis follow-up, and
prevented and was more experience
clinically safe,
in complex
suggesting freedom
from late thrombosis lesions
Colombo A, Sharp A. Lancet. 2009; 3 73:
Serruys PW, et al. Lancet; 2009; 373: 897
869

58. 3. Bioabsorbable Stents: A
self expanding drug-eluting non allergic
poly-lactic acid stent

59. Medronic’s Official
safety information
Contraindications Warnings
The Endeavor Sprint Zotarolimus- Please ensure that the inner
Eluting Coronary Stent System is package has not been opened or
contraindicated for use in: damaged, as this indicates the
1. Patients with a known sterile barrier has been breached.
hypersensitivity to zotarolimus or The use of this product carries the
structurally-related compounds. risks associated with coronary
2. Patients with a known artery stenting, including
hypersensitivity to the cobalt- subacute thrombosis, vascular
based alloy (cobalt, nickel, complications, and/or bleeding
chromium, and molybdenum). events.
3. Patients with a known This product should not be used in
hypersensitivity to patients who are not likely to
Phosphorylcholine polymer or its comply with the
individual Components and in recommended antiplatelet
4.patients with a known therapy
hypersensitivity or allergies to
aspirin, heparin, clopidogrel or
ticlopidine

61. My euharisties to all of you
Σας Εσταριστώ όλοσς σας
Nicholas Kounis

62. Nickel: a ubiquitous metal
Nickel allergy is most commonly associated with earrings and other jewelry for
body piercings that contain some nickel. Common sources of nickel exposure
include:
Jewelry for body piercings
Other jewelry, including rings, bracelets, necklaces and jewelry clasps
Watchbands
Clothing fasteners, such as zippers, snaps and bra hooks
Belt buckles
Hairpins
Eyeglass frames
Coins
Kitchen utensils
Paper clips
Pens
Keys
Tools, such as hammers and screwdrivers
Dental fillings
Artificial body parts (prostheses), such as artificial heart valves
Drinking water
Alkaline batteries
Cell phones
Nickel is also found in some foods, such as oatmeal, chocolate, nuts, beans and dried
fruit. Nickel may also be found in canned foods

63. Nickel allergy

64. People who are severely allergic to nickel as from earrings or belt
buckles, can actually develop a rash from eating foods high in
nickel.
In particular, chronic hand dermatitis has been associated with
eating foods high in nickel in patients with a known allergy. If you
are allergic to nickel and have a chronic rash, especially of your
hands, then consider a nickel-free diet. Try to avoid:
-Chocolate
-Potatoes
-Salmon
-Nuts and Legumes
(beans, lentils)
-Any canned food or
canned fruit
-Hot water from the tap
-Anything acidic (like
tomatoes) cooked in a
stainless steel pan
-Leafy green vegetables