SNAS and thyroid autoimmunity risk

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SNAS (Systemic nickel allergic syndrome may predispose susceptible individuals to developing chronic autoimmune thyroiditis (CAT)

 

Systemic nickel allergic syndrome as an immune-mediated disease with an increased risk for thyroid autoimmunity

Original Article:

Andrioli M, Trimboli P, Maio D, Persani L, Minelli M. Systemic nickel allergic syndrome as an immune-mediated disease with an increased risk for thyroid autoimmunity. Endocrine. 2015;50(3):807-810.

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Reviewed by Erin Wesner, BS, MSII & Jack Guccione, BS, MSIII. Loma Linda University School of Medicine

 

Keywords: Systemic nickel allergic syndrome, Nickel, Chronic autoimmune thyroiditis, Hashimoto

 

Key points:

  • Systemic nickel allergic syndrome (SNAS) may predispose susceptible individuals to developing chronic autoimmune thyroiditis (CAT)
  • Thyroid dysregulation is identified by elevated blood levels of thyroglobulin antibody and symptoms including fatigue, constipation, and weight gain.
  • Prior nickel sensitization with gastrointestinal and diffuse cutaneous symptoms and elevated thyroglobulin antibody may indicate SNAS-related thyroid disorder.
  • In over 200 patients studied, SNAS positive individuals showed a two-fold greater prevalence of CAT.

 

Introduction:

  • Chronic autoimmune thyroiditis (CAT) is the most common cause of hypothyroidism in areas with adequate iodine intake.1
    • CAT results from high circulating levels of anti-thyroid antigens and inflammatory mediators that cause gradual thyroid destruction.
    • Genetic, autoimmune and environmental factors (viruses, stress, hormones, pollution) have been identified as potential causes of CAT.2
  • Systemic nickel allergic syndrome (SNAS) is a chronic inflammatory disorder. It is characterized by a constellation of symptoms which can involve cutaneous, respiratory, gastrointestinal, and/or neurologic following systemic exposure to nickel (eg:  ingestion, implantation, inhalation) in individuals with prior nickel sensitization. (Table 1).1,3
    • This is in contrast to allergic contact dermatitis (ACD) wherein localized skin lesions erupt in response to direct contact with nickel (jewelry).
    • Approximately 20% of patients with a delayed allergy to nickel sulfate experience SNAS.1
    • SNAS is mediated through the release of cytokines by Th2 cells and Th1 cells, particularly IL-5 and IL-4.1,3
    • Intestinal biopsies taken from SNAS patients following nickel ingestion have shown increased amounts of CD4+ lymphocytes in the duodenal lamina propria and a decrease in the number of epithelial CD8+ lymphocytes due to apoptosis.3

Andrioli et al Article Review:

  • Andrioli et. al evaluated 239 patients over a 12-month period who had presented with immune-mediated inflammatory disease at the Department of Immune-Mediated Inflammatory Diseases of the Padre Pio Hospital in Campi Salentina, Lecce, Italy.1
    • All subjects underwent thyroid function testing as well as thyroid gland ultrasonography to identify thyroid disease.1
    • Thyroglobulin antibody (TGAb) (a blood test for thyroid dysfunction) was used to identify CAT in the study participants.
    • The authors defined SNAS by cutaneous and systemic manifestations, positive Ni patch testing in conjunction with an oral Ni challenge test, and clinical improvement following 4 weeks of a low Ni diet.1
      • 136 subjects met the diagnostic criteria for SNAS.1
      • Out of the remaining 103 subjects (non-SNAS), 40 tested positive for non-SNAS hypersensitivities (gluten, idiopathic dermatitis, lactose intolerance, allergic sensitivity to aeroantigens).1
      • The authors reported positive CAT in 26.5% of the SNAS group versus 12.7% in the non-SNAS group.
        • Notably, the global prevalence of CAT is estimated to be 1-2% in Caucasian women, but elevated in individuals with immune-mediated inflammatory disease, although the precise mechanisms remain unknown.1,4,5
        • For example, individuals with type 1 diabetes, celiac disease, Sjogren’s syndrome, rheumatoid arthritis and systemic lupus erythematosus all carry increased risk of developing CAT. None of these diseases were specifically identified in the non-SNAS group studied in Andrioli et al.1,6-9
      • Of note, TGAb levels were two fold higher in the SNAS group when compared to the non-SNAS group (19.9% vs. 7.8%).1

 

Key Points:

  • Andrioli et al. recognized a statically significant association between CAT and SNAS.1
  • The authors reported a two-fold greater prevalence of CAT in patients with SNAS (26.5%) compared to patients with other non-SNAS immune-mediated inflammatory disorders (12.7%).1
  • Based on Andrioli et al’s findings and literature review, the authors suggest that metal induced allergic reactions from nickel may promote increased production of TGAb through an autoimmune-inflammatory mechanism resulting in the development of CAT.
    • SNAS is associated with elevated levels of IL-4, a stimulator of B lymphocyte activity and differentiation.This cytokine may play a role in the production of TGAb in susceptible individuals when systemically exposed to nickel.
  • Concordant with these findings, elevated T-cell mediated pro-inflammatory cytokines are present in nickel-sensitized individuals, placing those with SNAS at a higher risk of developing autoimmune disorders (CAT).10
    • Further studies are warranted to define the pathogenic mechanism and protocol for screening for CAT in patients with SNAS.1

 

Table 1: Common SNAS and CAT individual and shared symptoms in descending order of frequency*10,11

Symptoms of SNAS10 Symptoms of CAT11 Shared symptoms10,11
Urticaria/angioedema Cold intolerance Fatigue
Dermatitis Impaired memory Edema
Recurrent abdominal pain Hair loss Constipation
Diarrhea Slowed movements Headache
Dyspepsia Brady cardia <60/min Bloating
Gastro-esophageal reflux Dry, coarse skin  
Itching Weight gain  
     
*SNAS – systemic nickel allergy syndrome; CAT – chronic autoimmune thyroiditis

 

References:

  1. Andrioli M, Trimboli P, Maio D, Persani L, Minelli M. Systemic nickel allergic syndrome as an immune-mediated disease with an increased risk for thyroid autoimmunity. Endocrine. 2015;50(3):807-810.
  2. Duntas LH. Environmental factors and thyroid autoimmunity. Ann Endocrinol (Paris). 2011;72(2):108-113.
  3. Braga M, Quecchia C, Perotta C, et al. Systemic nickel allergy syndrome: nosologic framework and usefulness of diet regimen for diagnosis. Int J Immunopathol Pharmacol. 2013;26(3):707-716.
  4. Weetman AP. Non-thyroid autoantibodies in autoimmune thyroid disease. Best Pract Res Clin Endocrinol Metab. 2005;19(1):17-32.
  5. Fallahi P, Ferrari SM, Ruffilli I, Elia G, Biricotti M, Vita R, Benvenga S, Antonelli A. The association of other autoimmune diseases in patients with autoimmune thyroiditis: Review of the literature and report of a large series of patients. Autoimmun Rev. 2016; 15(12):1125-1128.
  6. Appenzeller S, Pallone AT, Natalin RA, Costallat LT. Prevalence of thyroid dysfunction in systemic lupus erythematosus. J Clin Rheumatol. 2009;15(3):117-119.
  7. Biro E, Szekanecz Z, Czirjak L, et al. Association of systemic and thyroid autoimmune diseases. Clin Rheumatol. 2006;25(2):240-245.
  8. Counsell CE, Taha A, Ruddell WS. Coeliac disease and autoimmune thyroid disease. Gut. 1994;35(6):844-846.
  9. Piatkowska E, Szalecki M. Autoimmune thyroiditis in children and adolescents with type 1 diabetes. Pediatr Endocrinol Diabetes Metab. 2011;17(4):173-177.
  10. Ricciardi L, Carni A, Loschiavo G, et al. Systemic nickel allergy: oral desensitization and possible role of cytokines interleukins 2 and 10. Int J Immunopathol Pharmacol. 2013;26(1):251-257.
  11. Kostoglou-Athanassiou I, Ntalles K. Hypothyroidism – new aspects of an old disease. Hippokratia. 2010;14(2):82-87.