ReviewChronic autoimmune thyroiditis and rheumatic manifestations
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]
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