Elsevier

Joint Bone Spine

Volume 71, Issue 4, July 2004, Pages 275-283
Joint Bone Spine

Review
Chronic autoimmune thyroiditis and rheumatic manifestations

https://doi.org/10.1016/j.jbspin.2003.06.005Get rights and content

Abstract

A variety of rheumatic manifestations have been described in association with autoimmune thyroiditis. In the past, most of these manifestations were attributed to the underlying thyroid dysfunction, in particular hypothyroidism. However, a responsibility of the mechanisms involved in the autoimmunity rather than a direct action of thyroid hormones seems supported by the evidences that some rheumatic manifestations may occur even in euthyroid patients, or that they are more frequent in hypothyroid patient with autoimmune thyroiditis than in those without this disease. Rheumatic manifestations could be sometimes attributable to the autoimmune rheumatic diseases frequently associated with autoimmune thyroiditis, such as Sjögren’s syndrome, rheumatoid arthritis, systemic lupus erythematosus, or scleroderma. Among the most important or frequent rheumatic manifestations there are a mild non-erosive variety of arthritis, polyarthralgia, myalgia, and sicca syndrome without a true Sjögren’s syndrome. Although the possible pathogenesis of these manifestations is not completely established, some hypotheses may be proposed, including a role of autoantibodies characteristics of autoimmune thyroiditis, a possible overlap between autoimmune thyroiditis and some autoimmune rheumatic diseases, and a systemic inflammatory reaction associated with thyroiditis.

Introduction

Chronic autoimmune thyroiditis (CAT), also called chronic lymphocytic thyroiditis or Hashimoto’s thyroiditis, is the most common and extensively studied organ-specific autoimmune disorder in humans. CAT is characterized by diffuse lymphocytic infiltration of the thyroid gland, presence of antithyroid antibodies (ATA) in serum, clinical evidence of goitrous or atrophic gland and frequent thyroid dysfunction of varying degrees [1], [2]. Although the pathogenic mechanisms are still incompletely defined, the immune involvement in CAT is demonstrated by many findings, including early activation of CD4 T lymphocytes specific for thyroid antigen [3], expression of major-histocompatibility-complex (MHC) class II proteins induced by interferon-γ [4], self-reactive CD4 T cells stimulation of autoreactive B cells to secrete ATA [5], and cytokine-regulated apoptotic pathways [6].

A variety of rheumatic manifestations (RM) have been described in association with CAT. Most of these RM are usually attributable to the underlying thyroid dysfunction, mainly hypothyroidism [7], [8], which is in turn frequently linked to CAT [9]. However, in some cases, in particular when there is absence of thyroid dysfunction or when the treatment of thyroid disease induces the return to the normal thyroid function, two further possibilities can be considered to explain RM. The first derives from the evidence that, in a non-negligible number of patients, RM could be attributable to some autoimmune rheumatic diseases associated or overlapping with CAT, such as Sjögren’s syndrome (SS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or scleroderma [10], [11], [12], [13]. The other possibility suggests a direct responsibility of mechanisms involved in the thyroid autoimmunity. Thus, RM associated with CAT may be essentially classified in: (A) related to thyroid dysfunction; (B) secondary to autoimmune rheumatic diseases associated with CAT; (C) related to underlying thyroid autoimmunity.

Section snippets

Rheumatic manifestations due to autoimmune diseases associated with CAT

Due to the frequency of the CAT and ATA in the population, and particularly in women, the probability of the casual coexistence of two autoimmune diseases in the same subject is high. Thus, despite many papers continuously report cases of the association of CAT with other autoimmune diseases, definite non-casual associations are actually few (Table 1) [7], [14]. To approach these aspects, there are two modalities, one concerning the prevalence of CAT and/or ATA in autoimmune rheumatic diseases,

Rheumatic manifestations related to thyroid autoimmunity

RM associated with CAT may involve a variety of organs or tissues, even if the most representative are symptoms affecting joints, muscle and skin. The definition of “rheumatic” for some of these manifestations, i.e. PM, may seem inappropriate. However, in our or other experiences, it is not rare that patients with this mucinosis are seen in rheumatology [55]. The main RM found in 139 patients with CAT attending our Division of Rheumatology from 1981 for rheumatic complaints and without any

Conclusions

The most correct approach to the final conclusions of this review would obviously be a definitive statement on the relationship between RM and CAT. Unfortunately we still do not have any definitive demonstration. However, we believe that most aspects discussed above may be suggestive in favor of an actual pathogenic link between some RM and CAT. Furthermore, a lesson may derive from other diseases strongly suspected to be related to thyroid autoimmunity, such as chronic idiopathic urticaria [88]

References (106)

  • S Goucha et al.

    Association of seborrheic pemphigus and Hashimoto autoimmune thyroiditis. A propos of a further case

    Rev Med Interne

    (2002)
  • T Gambichler et al.

    Mid-dermal elastolysis associated with Hashimoto’s thyroiditis

    J Eur Acad Dermatol Venereol JEADV

    (1999)
  • H Hashimoto

    Zur Kenntniss der lymphomatösen Veränderung der Schilddrüse (Struma lymphomatosa)

    Arch Klin Chir

    (1912)
  • C.M Dayan et al.

    Chronic autoimmune thyroiditis

    N Engl J Med

    (1996)
  • A.P Weetman et al.

    Autoimmune thyroid disease: further developments in our understanding

    Endocr Rev

    (1994)
  • I Todd et al.

    Interferon-gamma induces HLA-DR expression by thyroid epithelium

    Clin Exp Immunol

    (1985)
  • G.F Del Prete et al.

    In vivo activated cytotoxic T cells in the thyroid infiltrate of patients with Hashimoto’s thyroiditis

    Clin Exp Immunol

    (1986)
  • G Stassi et al.

    Autoimmune thyroid disease: new models of cell death in autoimmunity

    Nat Rev Immunol

    (2002)
  • R Volpé

    Autoimmunity in the thyroid

  • R.H Scofield

    Autoimmune thyroid disease in systemic lupus erythematosus and Sjögren’s syndrome

    Clin Exp Rheumatol

    (1996)
  • J Karsh et al.

    Thyroid disease in Sjögren’s syndrome

    Arthritis Rheum

    (1980)
  • W.W Buchanan

    The relationship of Hashimoto’s thyroiditis to rheumatoid arthritis

    Geriatrics

    (1965)
  • M.D Gordon et al.

    Thyroid disease in progressive systemic sclerosis: increased frequency of glandular fibrosis and hypothyroidism

    Ann Intern Med

    (1981)
  • G Kaplan et al.

    Syndrome de Gougerot-Sjögren, connectivites et pathologie autoimmune

    Rev Rheum

    (1977)
  • F Gasches et al.

    Fréquence des maladie auto-immunes chez 218 patients atteints de pathologie thyroïdiennes auto-immunes

    Rev Méd Interne

    (1988)
  • P Humbert et al.

    Les syndromes auto-immune multiples (SAM)

    Ann Med Interne

    (1988)
  • B.U Hansen et al.

    Autoimmune thyroiditis and primary Sjögren’s syndrome: clinical and laboratory evidence of the coexistence of the two diseases

    Clin Exp Rheumatol

    (1991)
  • J Coll et al.

    High prevalence of subclinical Sjögren’s syndrome features in patients with autoimmune thyroid disease

    J Rheumatol

    (1997)
  • R Kolsi et al.

    Syndrome de Gougerot-Sjögren associé aux dysthyroïdies

    Rev Rhum

    (1990)
  • S.P Changlai et al.

    Objective evidence of decreased salivary function in patients with autoimmune thyroiditis (chronic thyroiditis, Hashimoto’s thyroiditis)

    Nucl Med Commun

    (2002)
  • C Vitali et al.

    Preliminary criteria for the classification of Sjögren’s syndrome. Results of a prospective concerted action supported by the European Community

    Arthritis Rheum

    (1988)
  • L Punzi et al.

    Thyroid gland disorders in primary Sjogren's syndrome.

    Rev Rhum Engl Ed

    (1996)
  • C.T Pease et al.

    Clinical, serological, and HLA phenotype subsets in Sjögren’s syndrome

    Clin Exp Rheumatol

    (1989)
  • H Moens et al.

    Hashimoto’s thyroiditis is associated with HLA-DRw3

    N Engl J Med

    (1978)
  • B.U Hansen et al.

    Clinical and immunological features of Sjögren’s syndrome in patients with primary biliary cirrhosis with emphasis on focal sialoadenitis

    Acta Med Scand

    (1988)
  • K.L Becker et al.

    The connective tissue diseases and symptoms associated with Hashimoto’s thyroiditis

    N Engl J Med

    (1963)
  • A.T Masi et al.

    Hashimoto’s disease: a clinical-pathological study with matched controls

    Lancet

    (1966)
  • L.M Mulhern et al.

    Hashimoto’s disease: a search for associated disorders in 170 clinically detected cases

    Lancet

    (1966)
  • A.J Silman et al.

    Autoimmune thyroid disease and thyroid autoantibodies in rheumatoid arthritis patients and their families

    Br J Rheumatol

    (1989)
  • C.M Deighton et al.

    Rheumatoid arthritis in thyroid disease positive and negative same-sexed sibships

    Br J Rheumatol

    (1992)
  • S Prahalad et al.

    Increased prevalence of familial autoimmunity in simplex and multiplex families with juvenile rheumatoid arthritis

    Arthritis Rheum

    (2002)
  • R.H Scofield

    Autoimmune thyroid disease in systemic lupus erythematosus and Sjögren’s syndrome

    Clin Exp Rheumatol

    (1996)
  • D Pyne et al.

    Autoimmune thyroid disease in systemic lupus erythematosus

    Ann Rheum Dis

    (2002)
  • A.T Chan et al.

    Thyroid disease in systemic lupus erythematosus and rheumatoid arthritis

    Rheumatology (Oxford)

    (2001)
  • D Mihailova et al.

    Autoimmune thyroid disorders in juvenile chronic arthritis and systemic lupus erythematosus

    Adv Exp Med Biol

    (1999)
  • K.L Becker et al.

    The connective tissue diseases and symptoms associated with Hashimoto’s thyroiditis

    N Engl J Med

    (1963)
  • F Gashes et al.

    Fréquence des maladies autoimmunes chez 218 atteints de pathologies thyroïdiennes autoimmunes

    Ann Méd Int

    (1998)
  • L.E Kahl et al.

    Prospective evaluation of thyroid function in patients with systemic sclerosis (scleroderma)

    J Rheumatol

    (1986)
  • M.B Gordon et al.

    Thyroid disease in progressive systemic sclerosis: increased frequency of glandular fibrosis and hypothyroidism

    Ann Intern Med

    (1981)
  • L De Keyser et al.

    Thyroid dysfunction in a prospectively followed series of patients with progressive systemic sclerosis

    J Endocrinol Invest

    (1990)
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      These manifestations are most commonly characterized by non-erosive arthritis and polyarthralgia [12]. While these manifestations occur at higher rates in the hypothyroid population, they have also been shown to occur in euthyroid patients with autoimmune thyroiditis [12]. Current hypotheses about the pathophysiology of this association include attack on synovial tissue from anti-thyroid autoantibodies, overlap between chronic autoimmune thyroiditis and other subclinical rheumatic disorders, and a systemic progression of an autoimmune process [12,14,15].

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