|Year : 2014 | Volume
| Issue : 4 | Page : 161-163
Acquired idiopathic pure white cell aplasia: A rare cause of agranulocytosis
Sadia Sultan, Syed Mohammad Irfan
Department of Hematology, Liaquat National Hospital, Karachi, Pakistan
|Date of Web Publication||13-Dec-2014|
Dr. Sadia Sultan
Department of Hematology, Liaquat National Hospital, Karachi
Source of Support: None, Conflict of Interest: None
Pure white cell aplasia (PWCA) is an exceedingly rare hematological disease of unknown origin exemplified by agranulocytosis, virtually lack of all granulocytic spectrums (from myeloblast to neutrophils) in the bone marrow with normal erythroid and megakaryocytic lineages. It has been associated with underlying autoimmune disorders, thymomas, chronic lymphocytic leukemia and drug induced or may be idiopathic. Here we report the case of a patient with this rare finding, who was admitted to our hospital with septicemia having agranulocytosis, multiple oral candidiasis, perianal abscess and right arm cellulitis. Bone marrow examination revealed absolute absence of all myeloid precursors cells. All diagnostic workup for secondary underlying cause were found to be negative and diagnosed as idiopathic PWCA. Immunosuppression with methylprednisolone pulse therapy was failed to induce neutrophils recovery. PWCA is a benign disorder, but have serious consequences due to threatening febrile neutropenia, disseminated fungal infection and septicemia. Needs urgent management depending upon underlying etiology.
Keywords: Agranulocytosis, idiopathic, pure white cell aplasia
|How to cite this article:|
Sultan S, Irfan SM. Acquired idiopathic pure white cell aplasia: A rare cause of agranulocytosis. J Appl Hematol 2014;5:161-3
| Introduction|| |
Pure white cell aplasia (PWCA) is a rare cause of neutropenia.  The diagnosis is based on bone marrow examination, which reveals virtually absent granulopoiesis, while erythropoiesis and megakaryocytopoiesis are intact. ,[ 2] Clinically, these patients often present with recurrent infections owing to very severe neutropenia.  PWCA may be drug-induced; however cases have also been reported in association with autoimmune disorders, thymomas or idiopathic. ,, Immunological pathogenesis has been demonstrated in some PWCA cases.  Surgical thymectomy or drug discontinuation may be clinically useful in secondary PWCA if associated with thymomas or drugs induced. Other treatment options include immunosuppressive therapies such as corticosteroids, intravenous immunoglobulin and cyclosporine. ,
| Case Report|| |
A gentleman 27 years, previously healthy presented to casualty with high-grade fever associated with rigors for 2 week, followed by progressive dysphagia for 5 days and the perianal discomfort for 3 days. The patient had denied any past history of recurrent pyogenic infection. His drug history was not significant. Physical examination revealed a pertinent finding of multiple oral candidiasis along with right arm cellulitis with no purulent discharge. Per rectal examination revealed perianal abscess. His blood pressure was 100/70 mmHg with tachycardia, heart rate of 126 beats/min regular and oral temperature of 39.5°C. Systemic examination was all unremarkable.
A complete blood count revealed very severe neutropenia with a total leukocytic count of 0.2 × 10 9 /L (absolute neutrophil count: 0.00 × 10 9 /L). Hemoglobin and platelet count were 12.2 gm/dl and 302 × 10 9 /L respectively. Routine biochemistry investigations revealed serum creatinine of 0.5 mg/dL, urea 21 mg/dL with normal electrolytes. Coagulation profile and liver function were also normal. The C-reactive protein was markedly elevated at 21 mg/L (normal <10 mg/L).
The peripheral blood smear examination showed agranulocytosis with identified few mature lymphoid cells and absence of blast cells. Bone marrow examination revealed significant finding of selective aplasia of granulocytic lineage, with essentially normal erythropoiesis and megakaryopoiesis. Leishman's stained bone marrow aspirate smear revealed well preserved erythroid precursors, but absence of granulopoiesis [Figure 1]. No dysplastic features were noted in aspirate. The hematoxylin and eosin stained trephine biopsy sections (×100) exhibited erythroid islands and well-distributed megakaryocytes, with no appreciating granulocytic lineage [Figure 2].
|Figure 1: Leishman's stain, bone marrow aspirate shows various erythroid precursors with absence of granulopoiesis|
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|Figure 2: H and E, Bone trephine section shows erythroid precursors and megakaryocytes, with the absence of granulopoiesis (Oil emersion, ×100)|
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A baseline chest radiograph was normal. To rule out underlying thymoma, computed tomography of the chest was done, however findings were unremarkable. In addition investigations showed a low-serum immunoglobulin IgG level of 5.5 g/L (normal: 7-16 g/L) and a normal IgA level of 0.8 g/L (normal: 0.7-4 g/L). An autoimmune profile was negative. An extensive work upincluding human immunodificiency virus, acuit hepatitis screening, test for rheumatoid factor and ANA were negative.
The patient received supportive management included intravenous broad spectrum antibiotics, incision and drainage of a abscess, an antifungal agent and a trial of methylprednisolone pulse therapy. Family refused for intravenous immunoglobulin due to financial constrains. The overall general condition and laboratory markers were not improved; eventually he was expired by the 4 th day of hospitalization due to severe septicemia.
| Discussion|| |
Pure white cell aplasia (PWCA) is an unusual hematological disorder demonstrated by the agranulocytosis, virtually lacking in all neutrophil series in the bone marrow and intact erythropoiesis and megakaryopoiesis. , It has been associated with autoimmune disorders, chronic lymphocytic leukemia, drug induced or may be idiopathic. , However majority of the cases have been associated with thymoma and thymic carcinoma.  Rarely patients with primary biliary cirrhosis or autoimmune hepatitis may demonstrate this rare phenomenon. , PWCA has been well reported previously with ibobrufen, chlorpropamide, and mesalazine drugs exposure. ,,
The PWCA was first described in 1983, and realized that not all "white cells" are affected, but rather only affects the neutrophils series accountable in 70% of cases.  Since then, a few additional cases have been reported in the literature. , Even though accurate reason for PWCA has not been elucidated, its relation with thymomas has been well described in the literature accountable in 70% of cases.  PWCA may recognize as an autoimmune disease, even the demonstration of an immune-mediated process by antibodies and/or T lymphocytes are unproven. ,
The secondary PWCA is thought to have an autoimmune pathogenesis with an antibody-mediated against the myelocytic precursor cells.  Few of the reported cases were revealed antineutrophil antibodies demonstration in PWCA.  However very severe neutropenia of unknown etiology should promptly evaluated by bone marrow examination for possible PWCA. PWCA should always be included in the differential diagnosis of isolated neutropenia.
Idiopathic or primary PWCA are extremely rare entity, often associated with secondary causes. Idiopathic entity seems to have aggressive clinical course with poor outcome having more risk of disseminated fungal infections and severe sepsis as indicated in our case report. To the best of our knowledge it is the first case reported from our part of the world.
Treatment approach should be adapted based on underlying disease.  However, it has been treated with a variety of immunomodulating agents, including steroids, cyclosporin, high-dose immunoglobulins and thymectomy when associated with thymoma. , Though PWCA is exceptionally rare in daily practice, but may be the underlying cause in isolated neutropenia.
| Conclusion|| |
Pure white cell aplasia is a rare disease. The pathogenesis is uncertain, likely to have immune mediated process. Once diagnosed, look for possible underlying cause. Idiopathic variant seems to have aggressive clinical course which necessitate the early treatment with immunosuppressive therapy.
| Acknowledgment|| |
We great fully acknowledge all the staff member of Hematology department of Liaquat National Hospital for their help and cooperation.
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[Figure 1], [Figure 2]