Rheumatology 2000; 39: 1437-1439
© 2000 British Society for Rheumatology
Letters to the Editor |
Novel clinical manifestations associated with antiphospholipid antibodies
Department of Medicine, Juntendo University Izu-Nagaoka Hospital, Shizuoka and
1 Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
SIR, Antiphospholipid antibodies (aPL) are known to be related to other clinical manifestations, such as cardiac valve lesions and haemolytic anaemia, in addition to the major clinical features of antiphospholipid syndrome (APS), such as thrombosis, recurrent fetal loss and thrombocytopenia [1]. Recently, we encountered and reported on patients with reactive haemophagocytic syndrome (HPS) or hypopituitarism (Sheehan's syndrome), possibly induced by the presence of aPL [2, 3]. Patient 1 was a 27-yr-old woman who showed anaemia and severe thrombocytopenia (white cells 7.0x103/mm3; red cells 411x104/mm3; haemoglobin 7.0 g/dl; platelets 0.2x104 /mm3). aPL were detected in the immunological examination (Table 1
). Clinical and laboratory examinations allowed us to exclude connective tissue diseases, such as systemic lupus erythematosus (SLE) and autoimmune haemolytic anaemia, and viral infections or malignancies as underlying disorders. Bone marrow smears showed an increase in mature-looking histiocytes scattered among the haematopoietic cells. The histiocytes showed marked phagocytosis of the haematopoietic cells, including megakaryocytes and erythroblasts. On the basis of these findings, the patient was diagnosed with HPS associated with the presence of aPL.
|
Thrombocytopenia and anaemia improved with steroid treatment, and her haemophagocytic phenomena disappeared during the second bone marrow aspiration 1 month after initiating steroid treatment. We also encountered a similar patient (patient 2 in Table 1
), though the details of the patient profile were not described in this letter. In addition to infections and malignancies, autoimmune diseases such as SLE are also known to be causative disorders of HPS [4–6]; however, HPS associated with aPL has not been previously reported. Increases in serum cytokines (such as tumour necrosis factor 
and interferon 
), ferritin and body temperature are generally observed in infection- or malignancy-associated HPS. Cytokines are thought to play an important role in the induction of HPS. However, these findings were not noted in our patients and other reported patients with autoimmune-associated HPS [5, 6]. This suggests that the underlying mechanism of autoimmune-associated HPS is different from that of infection- or malignancy-associated HPS. Binding of aPL-bound haematopoietic cells to the Fc receptor of phagocytes via the Fc portion of aPL may play a significant role in aPL-associated HPS [7].
Patient 3 was a 33-yr-old woman who complained of fatigue, failure to lactate and to resume menses after delivery. Hormonal examinations revealed low levels of adrenocorticotropic hormone (<5 pg/ml, normal range 9–52) and prolactin (<1.0 ng/ml, normal range 1.4–14.6) and magnetic resonance imaging examination disclosed empty sella of the hypophysis, which is a neuroradiological finding indicating pituitary necrosis. She showed positive reactions to aPL and thrombocytopenia (Table 1); however, it was not clear whether her thrombocytopenia was associated with HPS (as in the patients 1 and 2) because there was no bone marrow examination. There were no autoimmune connective tissue disorders noted after further investigation. Although it is difficult to prove directly the relationship between empty sella and thrombosis of pituitary vessels, she was thought to have Sheehan's syndrome associated with the presence of aPL. To date, adrenal insufficiency (Addison's disease), hyperthyroidism (Graves’ disease) and primary and secondary hypopituitarisms have been reported as aPL-related endocrine disorders [8–10]; however, our patient was the first reported case of Sheehan's syndrome associated with aPL. Although Sheehan's syndrome is thought to be induced by ischaemic hypophyseal necrosis induced by extensive blood loss associated with delivery, blood loss in this patient was not severe. APS and/or the presence of aPL may play an important role in the occurrence of such postparturient hypopituitarisms.
Recently, new criteria for the classification for APS were provided by Wilson et al. [11]. These criteria emphasize the importance of thrombosis and/or recurrent fetal loss but omit thrombocytopenia from the clinical criteria. The new laboratory criteria have more accurate specifications for detecting aPL in order to define the parameters for diagnosing APS, compared with previous criteria [12]. The laboratory findings of our three patients fulfilled the new criteria. However, the clinical findings did not meet the new criteria for diagnosing APS even though these patients were diagnosed with APS according to the previous criteria [12], because these patients have not developed any thrombosis affecting the deep veins or arteries, or recurrent fetal loss. This preliminary criterion for APS seems to be more suitable for confirming a diagnosis. On the other hand, the possibility of novel minor clinical symptoms associated with aPL, especially aPL according to the laboratory criteria given by Wilson et al. (such as those found in our patients), should not be overlooked, since aPL-related aetiological mechanisms, including the development of thrombosis, are not yet entirely clear. Further studies of additional associated features of APS should be encouraged.
Notes
Correspondence to: I. Sekigawa, Department of Medicine, Juntendo University Izu-Nagaoka Hospital, 1129 Nagaoka, Izu-Nagaoka-cho, Tagata-gun, Shizuoka 410–2295, Japan 
References
- Piette JC. Towards improved criteria for the antiphospholipid syndrome. Lupus1998;7:149–57.
- Ikeda K, Nawata M, Ando S et al. Antiphospholipid antibody-associated haemophagocytic syndrome. Rheumatology2000; 39:564–5.
[Free Full Text] - Ikeda K, Takahama M, Matsushita M et al. A case of hypopituitarism associated with antiphospholipid syndrome. Rheumatology2000; 39:447–8.
[Free Full Text] - Wong KF, Hui PK, Chan KC, Chan YW, Ha SY. The acute lupus hemophagocytic syndrome. Ann Intern Med1991;114:387–90.[Web of Science][Medline]
- Kumakura S, Ishikura H, Endo J, Kobayashi S. Autoimmune-associated hemophagocytosis. Am J Hematol1995;50:148–9.[Medline]
- Kumakura S, Ishikura H, Umegae N, Yamagata S, Kobayashi S. Autoimmune-associated hemophagocytic syndrome. Am J Med1997;102:113–5.[Web of Science][Medline]
- Manfredi AA, Rovere P, Galati G et al. Apoptotic cell clearance in systemic lupus erythematosus. 1. Opsonization by antiphospholipid antibodies. Arthritis Rheum1997;41:205–14.
- Arnason JA, Graziano FM. Adrenal insufficiency in the antiphospholipid syndrome. Semin Arthritis Rheum1995;25:109–16.[Web of Science][Medline]
- Hofbauer LC, Spitzweg C, Heufelder AE. Graves' disease associated with the primary antiphospholipid syndrome. J Rheumatol1996; 23:1435–7.[Web of Science][Medline]
- Andre M, Aumaitre O, Piette JC, Thieblot P. Hypopituitarism in a woman with a severe primary antiphospholipid syndrome. Ann Rheum Dis1998;57:257–8.
[Free Full Text] - Wilson WA, Gharavi AE, Koike T et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome. Report of an international workshop. Arthritis Rheum1999;42:1309–11.[Web of Science][Medline]
- Harris EN. A reassessment of the antiphospholipid syndrome. J Rheumatol1990;17:733–5.[Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||