Introduction

Many studies have demonstrated the existence of a familial aggregation of different systemic and organ-specific autoimmune diseases [1–15]. Furthermore, an increased prevalence of autoimmune diseases has been described among the relatives of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), scleroderma (SSc), and other connective tissue diseases (CTDs) [1–10].

The aim of the present survey was to obtain, by means of patient interviews, a preliminary estimate of the prevalence of systemic and organ-specific autoimmune diseases among the first- and second-degree relatives of Caucasian patients with CTDs or inflammatory arthritides being followed at the Rheumatology Unit and the Immuno-allergology Unit of the University of Pisa.

Materials and methods

Patients suffering from RA, spondyloarthropathies, or CTDs were invited to participate in this study during the course of one of their regular checkup visits. Patients with a diagnosis of osteoarthritis, osteoporosis, or fibromyalgia were recruited as controls.

Using a structured questionnaire designed ad hoc for this study, patients and controls were asked about the presence of the following autoimmune conditions among their first- and second-degree relatives: systemic autoimmune diseases (CTD, RA, or spondyloarthropathies), autoimmune thyroid disease (Hashimoto’s thyroiditis [HT] or Graves’ disease), psoriasis, vitiligo, discoid cutaneous lupus erythematosus, hemolitic anemia, idiopathic thrombocytopenia, insulin-dependent diabetes mellitus (IDDM), autoimmune hepatitis, primary biliary cirrhosis, coeliac disease, demyelinating diseases, myasthenia gravis, and idiopathic uveitis.

All of the variables were analyzed independently using the χ 2 test.

Results

Between June 2007 and January 2008, a total of 711 subjects (626 patients and 85 controls) were interviewed. The diagnoses of the patients are summarized in Table 1.

Table 1 The patient cohort (n = 711), grouped by diagnosis, and the reported occurrence of autoimmune conditions among their first- and second-degree relatives
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Three hundred ten patients (50%) versus 21 controls (25%) were found to have at least one first- or second-degree relative affected with an autoimmune condition (p < 0.0001). No significant differences between the disease subgroups were observed in the frequency of this association, as shown in Table 1.

Among the 310 patients, 197 (63%) had one relative, 83 (27%) had two relatives, 27 (9%) had three relatives, one (0.3%) had four relatives, and two (0.7%) had five relatives affected with an autoimmune disease. Among the controls, 17 (81%) had one affected relative and four (20%) had two affected relatives.

Therefore, in our patient cohort, a total of 473 affected relatives were reported. The most common conditions were organ-specific autoimmune diseases (in 358 subjects), beginning with 160 relatives (34%) suffering from autoimmune thyroid (AT) disease and followed by 112 relatives (24%) with psoriasis, 21 relatives with vitiligo, and 19 relatives with IDDM.

Systemic autoimmune diseases were reported in 126 relatives and were distributed as follows: 66 RA (14%), 16 sacroileitis, ten undifferentiated CTDs (UCTDs), eight SLE, seven SSc, eight psoriatic arthritis, six Sjögren’s syndrome (SS), three systemic vasculitis, one antiphospholipid syndrome, and one overlap syndrome.

Among the controls, organ-specific autoimmune diseases were observed in 19 relatives (thyroiditis, four; psoriasis, seven; vitiligo, two; IDDM, one) and systemic autoimmune diseases in seven relatives (three RA, one diabetes mellitus, one UCTD, one spondylitis, one overlap syndrome).

Among the patients, first-degree relatives were more frequently affected (13%) than second-degree relatives (6%), in the following order: siblings (27%), mothers (18%), offspring (14%), fathers (8%), grandparents (5%), and grandchildren (1%) (Table 2).

Table 2 Distribution of autoimmune diseases among the relatives of the patients
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A significant difference was observed in the prevalence of AT disease between the relatives of the patients and controls (3% versus 0.5%).

Discussion

In the present study, we evaluated by means of patient interviews the prevalence of organ-specific and systemic autoimmune diseases among the first- and second-degree relatives of patients with CTDs, RA, and spondyloarthropathies being followed at our hospital units.

We found a higher prevalence of autoimmune conditions among the relatives and in particular among the mothers and siblings of patients compared with controls. The most frequently reported condition was AT disease, which was observed in 34% of the affected relatives, followed by psoriasis (24%) and RA (14%).

On average, systemic and organ-specific autoimmune diseases occur in 5–8% of the general population. A familial aggregation for autoimmune conditions has been described in patients with CTDs, as well as AT disease and celiac disease [1–15].

To evaluate the familial aggregation of systemic autoimmune diseases, it is necessary to determine the prevalence of these conditions among individuals with different degrees of kinship. The majority of published studies have examined homozygous twins or individuals who share 50% of their genetic background (parents, brothers, dyzygous twins) compared with individuals who are not genetically related. For the CTDs, the data suggest a concordance rate of about 30% among homozygous twins and 2–5% among dyzygous twins and brothers, while in the general population the prevalence of these conditions varies between 0.1% and 1%.

In patients with CTDs, a familial aggregation for systemic and organ-specific conditions has been reported. In the majority of studies, first-degree relatives appear to be more frequently affected [1–10].

In the Grupo Latinoamericano de Estudio del Lupus Eritematoso cohort, a familial aggregation of autoimmune conditions among SLE patients was observed. It is interesting that, as in our study, an increased prevalence of AT disease was observed [2].

Similar results have been reported for SS, where relatives of SS patients were found to be primarily affected by AT disease, vitiligo, and IDDM [3, 4].

A higher occurrence of autoimmune disorders among the relatives of juvenile RA (JRA) patients has also been reported. In a recent study, a prevalence of 12.6% was observed among relatives versus 4% among controls. The only disorder that showed a statistically different rate of occurrence between JRA families and control families was HT, with the authors reporting a frequency of 6.1% and 5.1%, respectively, in the first- and second-degree relatives of JRA patients versus 2.1% and 1.3% in the relatives of controls [9].

Similarly, in our cohort, we found a high prevalence of AT disease among the first- and second-degree relatives of patients: 34% of the first-degree relatives and 3% of the second-degree relatives. It must be taken into account, in addition, that subclinical hypothyroidism has been associated with a number of conditions (including obstetric pathology, dementia, and cardiac complications) and AT disease may be difficult to diagnose [16].

One major limitation of the present study is the fact that the data were gathered indirectly, through interviews with patients and not with the relatives themselves. Nonetheless, we believe that our data are reliable since our evaluation was restricted to close relatives, regarding whom it can be supposed that the patients had a good knowledge of any eventual autoimmune conditions.