Kimberly P. Dunsmore, M.D.
University of Virginia Children's Medical Center
Charlottesville, Virginia

Introduction

Immune-mediated thrombocytyopenia (ITP) in childhood is a usually benign disorder with the majority of patients having resolution of the disease within six months. However, approximately 15% of pediatric patients develop the chronic form of the disease with thrombocytopenia lasting from months to years. ITP can also be the presenting feature of other autoimmune diseases such as systemic lupus erythematosus. The following case report illustrates how immune-mediated thrombocytopenia can be a presenting sign of a more global underlying autoimmune disorder.

Case Report

A 13-year-old female presented to the UVA Pediatric Hematology/Oncology clinic with a blotchy red rash on her lower extremites, buttocks and abdomen persistent for 2 months, microscopic hematuria, and thrombocytopenia with normal hemoglobin and white blood cell count. Her only bleeding symptom was mild epistaxis. She had a viral gastroenteritis 6 weeks prior to presentation but had otherwise been healthy. She was on no chronic medications and had used only diphenhydramine and acetaminophen in the past several months. A fracture of her wrist and toe had healed without difficulty or abnormal bleeding. Her family history was positive for arthritis in her father diagnosed during his teens and Crohn's disease in her paternal grandfather. Physical exam revealed mild facial flushing and a peculiar petechial rash on the flexor surfaces of her lower extremites bilaterally extending to her buttocks. The rash was macular, petechial but not palpable. She had other areas of isolated petechia and one ecchymoses from a blood draw. Initial CBC showed a hemoglobin of 13.7gm/dl, MCV 91, WBC 7.0 x 109/L with a normal differential and a platelet count of 58 x 109/L. Urinalysis showed 4-6 red blood cells per high power field but no other abnormalities. Bone marrow aspirate and biopsy revealed normal maturation of erythroid, myeloid and megakaryocyte lines but the erythroid series had slightly open chromatin suggestive of megaloblastic change. There were also cellular laden macrophages present. She underwent biopsy of the rash which revealed lymphocytic capillaritis. In view of these findings she underwent further laboratory testing. A red blood cell folate was normal, as was a serum vitamin B-12. Chem 17, hepatitis profile, HIV, immunoglobin levels, complement levels and anti-cardiolipin antibodies were all within normal limits. ANA titer was 1:160, homogenous, with negative anti-DNA, single and double-stranded and negative anti-ENA titers. She had a positive direct anti-platelet antibody. Over the next month, she developed increased menorrhagia, and her platelet count fell to 19 x 109/L. Prednisone was started at 30mg BID. Her platelet count returned to normal and her rash resolved but the rash and thrombocytopenia returned with tapering of her steroids. She elected not to have further steroid therapy, and when she had new oral and vaginal bleeding symptoms with a platelet count of 10 x 109/L, she received IVIG therapy. Once again her bleeding symptoms resolved and her platelet count normalized, but in two weeks her platelet count fell to 32 x 109/L. Over the next several months, her platelet count stabilized to the 50 to 100 x 109/L range. She developed recurrent non-herpetic mouth ulcers. Repeat bone marrow aspirate and biopsy 6 months after diagnosis revealed increased megakaryocytes and normal myeloid and erythroid series without evidence of megaloblastic change. Approximately one year after diagnosis, she developed swelling in her neck with symptoms of cold intolerance and fatigue. Thyroid ultrasound revealed no nodules, masses or abcesses. Her thyroid panel was normal, but her ANA was now 1:320 with a speckled pattern, and she had anti-microsomal thyroid antibodies. She was placed on Synthroid with improvement in her symptoms and subsequent fall in her thyroid antibodies. Her platelet counts have remained in the 50 to 100 x 109/L.

Conclusion

ITP, a usually benign condition of childhood, can be the presenting sign of a more global autoimmune disorder. This is more common in adolescent females who develop chronic ITP. The most common autoimmune disorder associated with ITP is systemic lupus erythematosus. The development of ITP can precede the diagnosis of lupus by months to years. The patient in the case report does not meet diagnostic criteria for lupus but has two other autoimmune disorders. Repeated clinical monitoring for development of signs and symptoms of autoimmune disorders, especially lupus, is indicated for adolescents who develop chronic ITP.