Sequential presentation of Hashimoto thyroiditis and idiopathic thrombocytopenic purpura followed by pernicious anemia and autoimmune atrophic gastritis with Helicobacter pylori infection: A potential case of autoimmune polyglandular syndrome type 3B

Key Figure.

Upper gastrointestinal endoscopy showing corpus/fundus-predominant mucosal atrophy with marked vascular visibility. a, esophagogastric junction; b, antrum; c, incisura angularis; d, fundus; and e and f, corpus.

A 70-year-old woman was referred to the Department of Hematology due to thrombocytopenia. The platelet count was 2.2 × 10⁴/μL with a high immature platelet fraction (IPF), while the red and white cell counts as well as white cell differential were normal (Table 1). Platelet-associated immunoglobulin G (PAIgG) was positive, albeit at a low level. Antinuclear antibodies (ANA) were positive, but complement levels were not decreased. The anti-Helicobacter pylori IgG antibody titer was in the upper limit of normal. No other underlying conditions causing thrombocytopenia were observed. Bone marrow examination showed a left-shift of megakaryocytes towards younger forms with less evidence of platelet production. Erythroid and myeloid precursors were normal. The patient had received levothyroxine (Thyradin-S) due to hypothyroidism at a previous hospital. As anti-thyroid autoantibodies were positive, the condition was attributed to Hashimoto thyroiditis (Table 1). The patient was diagnosed with idiopathic thrombocytopenic purpura (ITP), and low-dose prednisolone was started. However, because the patient was reluctant to take the drug, the dosages were kept to a minimum.

Table 1. Course of the test results related to APS

One year and 6 months after the first visit, the red cell indices gradually increased to reach macrocytic and hyperchromic ranges (Table 1). The level of serum vitamin B12 was low and anti-intrinsic antibody was positive (Table 1). Serum iron and ferritin levels were normal. Endoscopic examination of the upper gastrointestinal tract revealed marked atrophy of the gastric mucosa with inconspicuous rugal folds and visible submucosal vessels in the corpus and fundus, while the mucosa of the antrum was considered to be unaffected (Key Figure). The Campylobacter-like organism (CLO) test was negative. No neurological signs or symptoms were observed, but she complained of being lethargic. The patient was diagnosed with pernicious anemia (PA) associated with autoimmune atrophic gastritis, and vitamin B12 was administered intramuscularly and orally, readily leading to normalization of red cell indices and the vitamin B12 level (Table 1).

A second endoscopic examination performed 10 months after the first examination again disclosed corpus/fundus-predominant mucosal atrophy (Figure 1, top). Because the ¹³C urea breath test (UBT) was found to be above the cut-off value of 2.5‰ (Table 1), the patient received H. pylori eradication therapy, consisting of vonoprazan, amoxicillin, and clarithromycin, resulting in successful eradiation of the bacteria, confirmed by a negative UBT result. A third endoscopic examination after the eradication therapy disclosed O-2-stage atrophic gastritis according to the Kimura-Takemoto classification (Figure 1, bottom). The patient is currently doing well, receiving 50 μg of levothyroxine and vitamin B12 supplement therapy.

Figure 1.

Second (top) and third (bottom) upper gastrointestinal endoscopy. a and d, antrum; b and e, corpus; and c and f, fundus.

Here, we described a female patient in her 70s, who initially presented with Hashimoto thyroiditis and ITP and subsequently developed PA and autoimmune atrophic gastritis with H. pylori infection. Autoimmune polyglandular syndrome (APS) is defined by the combination of two or more autoimmune disorders involving endocrine and/or non-endocrine organs, and the syndrome has historically been classified as a very rare monogenic juvenile type (type 1) or a relatively common polygenic adult type (type 2) (Table 2). ¹ APS type 3, on the other hand, is defined by the association of an autoimmune thyroid disease with other autoimmune endocrine/non-endocrine condition(s) other than Addison disease. ^2,3 According to the classification scheme presented in Table 2 and updated version proposed by Betterle et al.,³ the current case represents the type 3B subtype. As total body stores of vitamin B12 are in the range of 2 to 5 mg, deficiency typically does not develop for at least one to two years, even if vitamin B12 intake or absorption ceases, ⁴ likely accounting for the interval between the initial presentation and manifestation of PA in this case. APS type 3B was formerly referred to as “thyro-gastric syndrome”, and it has been shown that 10–40% of patients with Hashimoto thyroiditis develop autoimmune gastritis. ^3,5 Thus, when treating patients with Hashimoto thyroiditis, we need to carefully monitor the red cell indices.

Table 2. Classification of APS

The course of this case was complicated by the co-occurrence of ITP and H. pylori infection. It is possible that ITP represented another autoimmune non-endocrine component of APS; in fact, there was a case report of APS type 3 associated with ITP. ² On the other hand, there is evidence that H. pylori serves as a trigger of autoimmune gastritis and PA.⁶ In this case, eradication therapy was delayed as the H. pylori IgG antibody titer was an equivocal value and the CLO test was negative. Thus, since each diagnostic test has its own disadvantages and limitations, other available methods should be considered when H. pylori infection is still suspected despite a negative test result. In this case, because the platelet count after eradication therapy remained in the range of 13.6 to 17.3 × 10⁴/μL without the administration of prednisolone, it is more likely that ITP at the initial presentation was simply due to H. pylori infection rather than a manifestation of APS.

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