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Autoimmune thyroiditis perdating the presentation of systemic lupus erythematosus: Two cases and a review of literature
Abhay I Ahluwalia
Classified Specialist Medicine and Endocrinologist, INHS Asvini, Colaba, Mumbai-400 005
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Dhir R, Ahluwalia AI, Sridhar J, Mani H, Pruthi H S, Shah K M. Autoimmune thyroiditis perdating the presentation of systemic lupus erythematosus: Two cases and a review of literature. Indian J Dermatol Venereol Leprol 2002;68:292-294
AbstractAutoimmune diseases are commonly encountered in dermatology practice. While the association of two autoimmune diseases in the same individual is not unknown, it is relatively rare for the second disease to be suspected based on cutaneous manifestations. We present two such cases wherein cutaneous manifestations were the first clue to the development of lupus erythematosus in a setting of autoimmune thyroiditis. Further, we have reviewed literature on this uncommon occurrence and discuss various aspects of this association.
Cutaneous manifestations are a fairly common occurrence in systemic autoimmune diseases. However, the diagnosis of a second autoimmune disease following dermatologic manifestations in a setting of thyroiditis is relatively infrequent. We present two such cases, wherein cutaneous manifestations were the first clue to the development of lupus erythematosus in patients with autoimmune thyroiditis.
A 22- year-old unmarried woman presented with weight gain, facial puffiness, dryness of skin and lethargy of three months duration. On examination she was also found to have bradycardia and a palpable thyromegaly. Thyroid function tests confirmed hypothyroidism with a serum thyroxine (T4) of 4.0 µgm/dl (normal range 5-11.5 µgm/dl),serum tri-iodo-thyronine (T3 ) of the ng/dl (nomal range 60-180 ng/dl) and serum thyroid stimulating hormone (TSH) level being 58 tdU/L (normal range 0.05-5.5 pJU/L).
Thyroid fine needle aspiration showed features suggestive of a classic lymphocytic (Hashimoto′s) thyroiditis and the patient tested positive for thyroid antimicrosomal antibodies (titer 1: 1600). Thus a diagnosis of autoimmune thyroiditis was established. At this point there were no manifestations of any other autoimmune disorder. Thyroid hormone replacement therapy with levothyroxine at a daily dose of 100 pg was begun and her symptoms gradually improved. Two months later she presented with a malar rash over the face with photosensitivity, and a discoid lesion on the back. Skin biopsy of the discoid lesion showed features of discoid lupus erythematosus with hydropic degeneration of the basal cell layer and a patchy predominantly peri-appendageal inflammatory infiltrate. Over the next month she also developed fever, arthralgias, inflammation of the metacarpophalangeal joints, and alopecia. Additional laboratory investigations at this point revealed anemia (hemoglobin being 8.5 gm/dl), raised sedimentation rate (ESR 52 mm fall in the first hour), and a positive serum anti-nuclear factor, thus cofirming the diagnosis of systemic lupus erythematosus (SLE). Oral steroids (prednisolone 40 mg daily) and chloroquine phosphate (500mg daily) were added to her treatment regimen, and she has shown a good therapeutic response and is presently on maintenance therapy.
A 33-year-old woman, a mother of two, who presented with weight gain and a thyromegaly, was found to be biochemically hypothyroid (serum T4-3.5 µgm/dl, serum T3-44ng/dl and TSH - 100plU/L). Thyroid antimicrosomal antibodies were present at a titer of 1:3200 and thyroid fine needle aspiration showed features of a lymphocytic thyroiditis. Thyroid hormone replacement therapy was begun. Five years after the onset of hypothyroidism, she presented with joint pains, alopecia, oral ulcers and recurrent ulceration over the legs. Histologic findings on skin biopsy were consistent with subacute cutaneous erythematosus (SCLE). She tested positive for anti-nuclear factor. Presently, she is being treated with prednisolone and chloroquine, while thyroid hormone replacement is being continued.
Autoimmune diseases are multifactorial acquired disorders that likely result from a complex interplay of a number of predisposing genetic and environmental risk factors,, Autoimmune thyroiditis may appear in the course of other nonorgan-specific autoimmune diseases such as Sjogren syndrome, polymyalgia rheumatica, temporal arteritis, relapsing polychondritis, type 1 diabetes mellitus, pernicious anemia and thrombocytopenia. In their series of 160 cases of Sjogren′s syndrome, Ramos Casals found that 36% of patients had evidence of thyroid disease, with 20% having autoimmune thyroiditis and 16% having non-autoimmune thyroid disease. The bulk of the patients with autoimmune thyroiditis showed hypothyroidism. Thyroid disease was more common in patients with Sjogren′s syndrome than in age and gender-matched controls. In another study, Mihailova et al found autoimmune thyroiditis in 44.4% of children with juvenile chronic arthritis, although 85.2% of these were euthyroid. Thyroid gland disorders were also detected in children suffering from SLE. Thyroglobulin antibodies were positive (1:80-1:5120) in 7 out of 12 cases while antinuclear antibodies (1:3201:2560) were detected in 8 out of 12 cases. Others have also documented the association between thyroiditis and SLE., An association of autoimmune thyroiditis and seronegative systemic lupus erythematosus (SLE) has also been reported. At the same time, the development of systemic autoimmune diseases in a setting of established thyroiditis is also described, albeit less frequently. These second autoimmune disorders have included SLE, scleroderma, and ankylosing spondylitis.,,,,
Autoimmune diseases are commonly encountered in dermatology practice since many such conditions may present as skin disorders. This is especially true in the case of SLE, wherein localized cutaneous forms such as DLE and SCLE are common in the absence of full-blown systemic disease. Cutaneous manifestations also occur in association with thyroid disorders, the most common being various forms of cutaneous mucinosis has been reported to be Hashimoto′s thyroiditis. Other cutaneous disorders have also been associated with autoimmune thyroiditis including urticaria, angioedema and lichen amyloidosis., We have come across only one other case in literature of SCLE occurring in association with autoimmune thyroiditis, reported by Ilan and colleagues. Their patient, however, also had co-existing Sjogren′s syndrome and developed subacute cutaneous lupus two years after onset of thyroiditis. This late development of SCLE is in keeping with our second case who also presented with cutaneous lupus years after diagnosis of thyroiditis. We emphasize that cutaneous manifestations in a setting of thyroiditis merits investigation for other systemic autoimmune diseases, since the systemic manifestations by themselves maybe falsely attributed to the thyroid disorder thereby missing a diagnosis of a second autoimmune disease.
The pathogenetic mechanisms of development of other autoimmune diseases in patients with thyroiditis are unknown. The similarity of histologic lesions in thyroiditis and Sjogren s syndrome supports a common pathogenetic mechanism. In addition, a similar genetic background could predispose individuals to both diseases. Thyroglobulin directed antibodies have been suggested as a possible target in the occurrence of mixed SLE and thyroiditis, with transition from polyreactive proteolytic activity to autoantigen directed activity. Whereas the diverse clinical. manifestations of many autoimmune diseases cannot be simply explained by the existence of autoantibodies, idiotypic dysregulation may provide an alternative explanation. Tomer et al have shown that it is possible to induce both non-organ specific systemic autoimmune diseases such as SLE and antiphospholipid syndrome, as well as experimental autoimmune thyrojditis by idiotypic manipulation in naive mice. Other etiologic considerations that have been evoked describe the occurrence of mixed autoimmune diseases include drugs and viral infections. Drug-induced cutaneous lupus, has not, however, been described with thyroid hormone replacement therapy. On the other hand, infection with hepatitis C virus may cause multiple autoimmune manifestations.
In summary, we have described two cases with different cutaneous presentations of lupus in patients with known autoimmune thyrojditis. Awareness of this association is important for dermatologists since, in a setting of autoimmune thyroiditis, cutaneous manifestations may be the ffrst clue to the development of SLE for other systemic manifestations may be mistaken to be due to the thyroid disorder per se. Further, the development of the lupus may be as much as years later, especially in the case of SCLE. The manifestations of lupus respond to therapy with steroids and chloroquine. However, therapy of the lupus may have to be continued for a long time, since discontinuation of therapy has been reported to precipitate thyrotoxic crisis. Although thyroid involvement is not presently included in the classification criteria of SLE, the lookout for the association of thyroiditis and cutaneous lupus may prompt the inclusion of thyroiditis within the broader spectrum of SLE.
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