A Letter

Multiple Autoimmune Syndrome: Celiac Disease, Hashimoto's Thyroiditis, and Systemic Lupus Erythematosus  

Nabil Belfeki1 , Souheil Zayet2 , Imed Ben Ghorbel1 , Mohamed Habib Houman1
1 Department of Internal Medicine, University Hospital of La Rabta, Tunis, Tunisia
2 Department of Infectious Disease, University Hospital of La Rabta, Tunis, Tunisia
Author    Correspondence author
International Journal of Clinical Case Reports, 2017, Vol. 7, No. 1   doi: 10.5376/ijccr.2017.07.0001
Received: 24 Feb., 2017    Accepted: 15 Mar., 2017    Published: 05 Apr., 2017
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Preferred citation for this article:

Belfeki N., Zayet S., Ghorbel I.B., and Houman M.H., 2017, Multiple autoimmune syndrome: celiac disease, hashimoto’s thyroiditis, and systemic lupus erythematosus, International Journal of Clinical Case Reports, 7(1): 1-3 (doi: 10.5376/ijccr.2017.07.0001)


Multiple autoimmune syndrome is the association of three or more autoimmune diseases in the same patient. We report the case of a 24-year-old woman with a medical past history of celiac disease since the age of 3. She complained of fatigue, malar rash, and paresthesia of the lower limbs. Physical examination objectified fever at 38°C and butterfly rash. Cell blood count showed leucopenia and lymphopenia. Thyroid tests concluded to primary hypothyroidism. Immunological investigations revealed positive antinuclear antibodies (1/3200), anti-DNA, and thyroperoxydase antibodies. The HLA haplotype typing was A1 A26 B50 B16 DR3 DR52 DQ2. The diagnosis of multiple autoimmune syndrome associating systemic lupus erythematosus, celiac diasese, and Hashimoto’s thyroiditis was retained. The patient was treated with hydroxychloroquine 400 mg/day and L-thyroxine 100 µg/day. The global outcome was favorable and the patient was free of symptoms. The decline is 10 years. The current case is unique in this aspect that the combination of these three autoimmune disorders has rarely been reported in the past.

Multiple autoimmune syndrome; Systemic Lupus Erythematosus; Celiac disease; Hashimoto’s thyroiditis


Autoimmune diseases are known to have association with each other but it is very rare to see multiple autoimmune diseases in one patient. The combination of at least three autoimmune diseases in the same patient is referred to as multiple autoimmune syndrome (MAS) (Humbert and Dupond, 1988).We report a case of MAS in a 24-year old girl who was diagnosed to be suffering from Hashimoto's thyroiditis, celiac disease, and systemic lupus erythematosus (SLE).


1 Case Report

A 24-year-old woman had a family past history of celiac disease with her brother and personal past history of celiac disease since the age of 3. The diagnosis of celiac disease was retained at the age of 3 since the patient had abdominal pain, subtotal villous atrophy on jejunal biopsy, and positive Ig A anti transglutaminase and Ig A anti endomysium antibodies. The patient’s symptoms improved after a gluten-free diet. At the age of 24, she complained of fatigue, malar rash, and joint pain on wrists and fingers. On examination, she had fever at 38°C. Her weight was 51 kg for a height of 152 cm. She had a smooth non tender goiterous swelling in the front of her neck, measuring about 5×6 cm. She presented a butterfly malar rash and reported photosensitivity. Musculoskeletal and abdominal examinations were unremarkable and urine sticks were negative. First hour laboratory tests showed leucopenia (3 800/mm3), lymphopenia (800/mm3), and an erythrocyte sedimentation rate of 57 mm. Serum protein electrophoresis showed hypergammaglobulinemia (25 g/l). Thyroïd profile showed high thyroid stimulating hormone (TSH) (65 µUI/ml) and low T4 (4 ng/L). Immunological investigations showed that antinuclear antibodies (1/3200), anti-DNA, and anti-thyroperoxydase antibodies were all positive. Complements fractions (C3, C4, and CH50) were normal. Thyroid echography showed diffuse nontoxic goiter. The HLA haplotype typing was A1 A26 B50 B16 DR3 DR52 DQ2. Based on clinical and laboratory findings, the diagnosis retained was of multiple autoimmune syndrome associating systemic lupus erythematosus (according to the American College of Rheumatology criteria for classification of systemic lupus erythematosus (Hocheberg, 1997)), Hashimoto thyroiditis and celiac disease. Besides a gluten free diet, the patient was treated with hydroxychloroquine (400 mg/day) and L-thyroxine (100 µg/day). She responded positively to this treatment and is being regularly followed up in our outpatient clinic. Ten years later, no relapse was noted.


2 Discussion

Autoimmune diseases encompass a wide spectrum of diseases, from organ specific Hashimoto's thyroiditis to systemic diseases such as systemic lupus erythematosus. Although the etiology is still poorly understood, genetic, immunological, hormonal and environmental factors are the major predisposing and triggering factors (Szyper-Kravitzm et al., 2005). Studies documenting increased risk of developing autoimmune diseases (ADs) have shown that these conditions share several immunogenetic mechanisms (Koning, 2015). HLA A1B8DR3 haplotype is associated to celiac disease (Castiblanco et al., 2015). This haplotype is seen in systemic lupus erythematosus in 40 to 70% of cases (Sparks and Costenbader, 2014). Hence, the two diseases can occur in the same patient as they share common genetic background. The multiple autoimmune syndrome were described by Humbert and Dupond in 1988 as a syndrome(s) consisting of the presence of three or more well characterized ADs in one patient (Humbert and Dupond, 1988). This definition is based on 91 reported cases of such associations in the literature (Mohan and Ramesh, 2003). MAS can be classified into three groups according to the prevalence of their associations with one another. Type 1 MAS includes myasthenia gravis, thymoma, polymyositis, and giant cell myocarditis. Type 2 includes Sjögren's syndrome, rheumatoid arthritis, primary biliary cirrhosis, scleroderma, and autoimmune thyroid disease. Type 3 groups together autoimmune thyroid disease, myasthenia gravis and/or thymoma, Sjögren's syndrome, pernicious anaemia, idiopathic thrombocytopenic purpura, Addison's disease, insulin-dependent diabetes, vitiligo, autoimmune haemolytic anaemia, SLE, and dermatitis herpetiformis (Mohan and Ramesh, 2003). Systemic lupus erythematosus (SLE), autoimmune thyroid disease (AITD), and Sjögren's syndrome together were the most frequent ADs encountered (Anaya et al., 2012). For our case, with the presence of Hashimoto’s thyroiditis and SLE, our patient seems to qualify, but only partially, with type 3 MAS. Celiac disease, though an immune mediated disorder, is not included in the classification of MAS and usually associated to type 1 diabetes mellitus (Zhao et al., 2016). The review of literature revealed only one case report with these conditions occurring in a pediatrician patient although there have been reports of variable association between any two of these conditions. In Fact, Latif et al reported the case of an 11 year-old patient presenting general symptoms, constipation, joint pain, and goiter. The final diagnosis was MAS. NSAIDS with short course of corticosteroids were given for SLE, levothyroxine for Hashimoto’s thyroiditis, and gluten free diet was advised for coeliac disease. The patient responded positively to this treatment (Latif et al., 2010). A patient suffering from one autoimmune disease has 25% chances of acquiring another autoimmune disease (Mohan and Ramesh, 2003). The association of celiac disease and systemic lupus erythematosus is uncommon. Few cases were reported (Zitouni et al., 2004; Hrycek and Siekiera, 2008; Freeman et al., 2008). In a case series of 30 patients affected with MAS, celiac disease was associated to Hashimoto’s thyroiditis in 9 patients (Giardino et al., 2011). This association is frequent and well known in the literature with as prevalence estimated at 5.4%. This could be explained by the sharing of a common genetic predisposition by the two disorders, namely the DQ2 allele (Kumar et al., 2001). The association of Hashimoto’s thyroiditis with systemic lupus erythematosus has been reported in adults in a range of 7.5% to 8.9% (Zitouni et al., 2004).


3 Conclusions

According to definition; the combination of three autoimmune diseases in our patient qualifies for the diagnosis of MAS. This case illustrates the importance of regular follow-up of each patient with autoimmune disease, in order to detect other associated autoimmune conditions. Genetics background plays an important part in its occurrence.


Authors’ contributions

Nabil Belfeki and Souheil Zayet followed the patient at the outpatient clinic. Nabil Belfeki and Imed Ben Ghorbel performed the bibliography for this case. Mohamed Habib Houman supervised the whole case before its submission in International Journal of Clinical Case Reports. All authors read and approved the final manuscript.



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PMid:25437282 PMCid:PMC4250576


Zitouni M., Daoud W., Kallel M., et al., 2004, Systemic lupus erythematosus with celiac disease: a report of five cases, Joint Bone Spine, 71: 344-346



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