Ulcerative colitis and primary sclerosing cholangitis as part of autoimmune polyglandular syndrome type III

Ulcerative Colitis and Primary Sclerosing Cholangitis as Part of Autoimmune Polyglandular Syndrome Type III

To the Editor:

Autoimmune polyglandular syndrome (APS) is an autoimmune disease affecting 2 or more endocrine organs; generally 4 types of APS are distinguished. APS type III as a subdivision of type II is characterized by autoimmune thyroid disease with other autoimmune disorders but without adrenal insufficiency.¹

We report a case of a 37-year-old man initially diagnosed with ulcerative colitis (UC) who was found to have APS type III. In a 10-year period different clinical, laboratory, and radiological examinations revealed the presence of coexisting UC, primary sclerosing cholangitis (PSC), insulin-dependent diabetes mellitus (IDDM), Hashimoto's thyroiditis, vitiligo, and rheumatoid arthritis (RA). The rare combination of these different, severe syndromes has not been reported before.

Inflammatory bowel diseases are unusual as part of APS; however, celiac disease is the most commonly associated, immune-mediated enteral disease in APS type III.² The presence of UC in any type of APS has not been documented before.

The medical history of this 37-year-old man started in 1994 when he was diagnosed with UC pancolitis accompanied by PSC involving both the extra- and intrahepatic bile ducts. IDDM developed 2 years after the diagnosis of UC and PSC. After a long-lasting period with chronic mild activity, he had a flare-up of UC with 5–10 bloody stools daily in 2006. Control endocrine examinations performed in May 2007 revealed an elevated thyroid-stimulating hormone level of 199.5 mIU/L and an abnormal anti-thyroid peroxidase antibody level of 311.7 iu/mL, indicating Hashimoto's thyroiditis. Therefore, L-thyroxin treatment was administered. In October 2007, because of the continuous endoscopic and clinical activity of UC despite the usual mesalazine and azathioprine treatment, cyclosporine was introduced but had to be discontinued because of the development of weakness and myalgia. In the same year, patchy vitiligo was observed affecting the whole body. In March 2008 the presence of a deforming polyarthritis involving both wrists, elbows, knees, and the small joints of the hands and feet was noted. The diagnosis of RA was established based on symmetric polyarthritis and the typical radiographic changes, including multiple juxta-articular erosions in the metacarpo-phalangeal, proximal interphalangeal, intercarpal, and radiocarpal joints and multiple ankyloses in the intercarpal joints (Fig. 1). IgM rheumatoid factor and antimutated citrullinated vimentin antibodies were negative; dehydroepiandrosterone sulfate, adrenocorticotropic hormone, and cortisol test were also within the normal range. Coexistence of UC, PSC, Hashimoto's thyroiditis, IDDM, vitiligo, and RA indicated the diagnosis of APS type III. Gluten sensitive enteropathy was excluded by serological examinations and duodenal biopsy.

Because of his erosive and destructive RA and continuously active UC, biological treatment with infliximab had to be initiated in November 2008 and he has been placed on the liver transplant waiting list. After the 3-infusion induction therapy, the debilitating symptoms of rheumatoid arthritis showed significant improvement, UC remitted, and, surprisingly, the years of lasting increase of serum alkaline phosphatase level stopped and a more than 40% reduction from serum level of 3170 U/L to 1405 U/L was observed.

Both genetic and environmental factors are suspected to play a role in the accumulation of these autoimmune diseases in APS type III. Although most of the gene mutations in APS type III are unknown, a correlation between major histocompatibility complex (MHC) class II and APS type III has been described and an increased prevalence of HLA-DR3 and DR4 has been found.³

UC has never been reported in APS patients before. However, UC is known to be associated with PSC and RA. About 4%–7.5% of patients with UC have PSC.⁴ Coexistence of UC and RA is relatively rare (0.8%).⁵

To our knowledge this is the first reported case with concomitant UC, PSC, IDDM, Hashimoto's thyroiditis, vitiligo, and RA and the lack of Addison's disease, which is the hallmark of APS type II; coexistence of these diseases fulfilled the criteria for APS type III. Treatment of all components of the syndrome is difficult because of developing intolerance and interactions between the drugs and the underlying diseases. Blockade of tumor necrosis factor-α (TNF-α) by infliximab, which plays an important role in the pathogenesis of multiple autoimmune diseases, can be effective in UC and RA.

There is only 1 double-blind, placebo-controlled, randomized study of the efficacy of infliximab in a small group of PSC patients, in which infliximab failed to improve PSC after 6 infusions.⁶ In our case the initial results with infliximab are promising not only in the treatment of UC and RA, but also in PSC, making it possible to avoid urgent liver transplantation.

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