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Leukemia Research 33 (2009) e95–e97

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Leukemia Research

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phy of the paranasal sinuses after 1 month showed no mass withinthe sinuses and there was regression of bone destruction.

The patient was hospitalized in December 2007 with thecomplaints of fever, cough, sputum, and deterioration of general

etter to the Editor

ntineutrophil cytoplasmic antibody associated vasculitis inne patient with severe aplastic anemiaescription of the first case

. Introduction

Antineutrophil cytoplasmic antibody (ANCA)-associated vas-ulitides might present with joint symptoms and sinusitis. Rarely,lassical destructive rheumatoid arthritis might be complicated byNCA-associated microscopic polyangiitis or Wegener’s granulo-atosis [1–4].The association between rheumatoid arthritis and aplastic ane-

ia is well-known in literature. Nevertheless, aplastic anemia andNCA-associated vasculitis has not been reported before. Here, weresent our patient previously diagnosed with erosive rheumatoidrthritis, who developed severe aplastic anemia and later diagnosedo have ANCA-associated vasculitis.

. Case report

Our 44-year-old female patient had been diagnosed withheumatoid arthritis in 2004 because of arthralgia and arthritis.he had been administered nonsteroidal antiinflammatory drugs,teroids, salazopyrine and methotrexate. She was hospitalized inrakya University Medical Faculty, Division of Rheumatology inebruary 2007 because of petechiae and ecchymoses. On phys-cal examination, her temperature was 37.6 ◦C; other vital signs

ere normal. She had conjunctival pallor; and there were petechiaend ecchymoses all over her body. There was no lymphadenopathyr hepatosplenomegaly. Whole blood count showed hemoglobin,g/dL; hematocrit, 22.4%; MCV, 86 fL; leucocytes, 1800 mm−3; neu-

rophils, 350 mm−3; platelets, 3000 mm−3. The peripheral bloodmear showed 20% neutrophils, 1% eosinophil, 64% lymphocytes,% monocytes. Routine biochemical tests were within normal lim-

ts. The absolute reticulocyte count was 25,000 mm−3. The bonearrow aspiration was hypocellular and there were 72% lym-

hocytes. The bone marrow biopsy yielded hypoplasia with 10%ellularity. The marrow was replaced with fat cells and scat-ered lymphocytes and stromal cells (Fig. 1). Urinary sedimentas nonsignificant. HBsAg, anti-HCV, and anti-HIV were all neg-

tive. Flow cytometry showed expression of CD55 and CD59 onrythrocytes and neutrophils. Chest X-ray and abdominopelvicltrasonography were normal. The patient was diagnosed asevere aplastic anemia and given immunosuppressive treatmentonsisting of antithymocyte globulin and cyclosporine A. Fromhe end of immunosuppressive treatment at February 2007ntil the beginning of September 2007, the highest hemoglobin

evel reached 8.2 g/dL with erythrocyte transfusions; the high-st leucocyte and neutrophil counts were, respectively, 930 and00 mm−3; the platelet count was always below 10,000 mm−3

nd she was transfused with platelet suspensions whenevereeded.

145-2126/$ – see front matter © 2009 Elsevier Ltd. All rights reserved.oi:10.1016/j.leukres.2009.01.015

The patient was rehospitalized in September 2007 with swellingover both eyes, and a large ecchymosis on the right half of the face.The temperature was 38.4 ◦C, there were ecchymoses and edemaover both orbits and the surrounding tissue; the right nasal pas-sage was obstructed. There was no organomegaly. Hemoglobin was8.6 g/dL; hematocrit, 30.2%; MCV, 86 fL; leucocytes, 1000 mm−3;neutrophils, 250 mm−3; platelets, 10,000 mm−3. Cranial tomog-raphy was within normal limits. Computed tomography of theparanasal sinuses showed a mass 5 cm × 4 cm × 4 cm in diameterwhich filled almost completely and caused destruction of the maxil-lary, ethmoid, and sphenoid sinuses. After obtaining an urgent deeptissue biopsy meropenem 1 g (thrice a day) and classical ampho-tericin B 1 mg/(kg day) were started to be given. The histopathologicexamination of tissue biopsies showed a necrotizing granuloma-tous reaction deep on the respiratory mucosal tissue. Geographicnecrosis with palisating histiocytes and mixed type inflammatoryinfiltrate were seen on microscopic examination. There was nosign for fungal infection on PAS stain. Elastica van Gieson stain didnot show any vascular damage for a vasculitis. The final diagno-sis was necrotising granulomatous inflammation (Figs. 2 and 3).The rheumatoid factor was negative, antinuclear antibody (ANA)was positive at a dilution of 1/1280 in a nuclear and dot pattern, P-ANCA and MPO-ANCA were positive at a titer of 1/160. The patientwas diagnosed with ANCA-associated vasculitis. The mass in theparanasal sinuses and edema of the face which did not regress after3 weeks of antibiotics, started to regress after methylprednisolone1 g/day administered for 3 consecutive days. Thereafter, she waskept on methylprednisolone 60 mg/day. The computed tomogra-

Fig. 1. Bone marrow is devoid of hematopoietic elements showing largely fat cells(H&E ×12.5).

e96 Letter to the Editor / Leukemia Re

Fig. 2. Geographic necrosis in a granulomatous reaction. Arrows point the necrosis(H&E ×12.5).

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Fig. 3. Palisating histiocytes around the necrosis (arrow) (H&E ×100).

ondition. She died because of pneumonia which did not regressfter broad-spectrum antibiotics.

. Discussion

The coexistence of vasculitis and malignancy is well-known5–13]. The prevalence of malignancy in patients with vasculitisaries between 3 and 8% [14]. The most frequently diagnosed malig-ancies in patients with vasculitis are hematological malignancies15,16].

ANCA are antibodies which develop directly against neutrophilranules and monocyte lysosomes [2]. The two main ANCA anti-ens are MPO which exists in azurophilic granules and PR3 whichxists both in azurophilic granules and secretory vesicles [17]. Vas-ulitides associated with lymphoma are frequently ANCA-negative10].

It is known that aplastic anemia might coexist with rheumatoidrthritis or might be secondary to drugs used for rheumatoid arthri-is. Until now, there has been no report on an association betweenplastic anemia and ANCA-associated vasculitis. It was stated thathe incidence of hematological malignancies was increased inatients with Wegener granulomatosis [13].

Many different mechanisms might be operating in vasculitidesssociated with malignancies. Among these are immune complex

ormation, the polyclonal activation of B lymphocytes, the activityf monoclonal immunoglobulins, the direct influence of malignan-ies on vessel wall and the effects of drugs used for cancer therapy11,12].

search 33 (2009) e95–e97

We presented our patient with severe aplastic anemia whowas given immunosuppressive therapy consisting of antithymo-cyte globulin and cyclosporine A. Nevertheless, she did not respondto this therapy. She developed a destructive paranasal sinus massduring follow-up, and diagnosed with ANCA-associated vasculi-tis after finding a positive ANCA and a necrotising granulomatousinflammation on tissue biopsy. Her response to corticosteroids wassatisfactory; however, she died because of pneumonia.

We reported this case because although there is an estab-lished connection between aplastic anemia and rheumatologicdiseases like rheumatoid arthritis and systemic lupus erythe-matosus, the coexistence of aplastic anemia and ANCA-associatedvasculitis has not been reported before. When patients withhematological malignancies develop systemic symptoms, besidesinfectious causes, systemic vasculitides should be born inmind.

Conflict of Interest

None.

References

[1] Palomar R, Castaneda O, Rodrigo E, Ruiz San-Millan JC, Martin Gago J, Morales P,et al. Microscopic polyangiitis in a patient with rheumatoid arthritis. Nefrologia2005;25:438–41.

[2] Ortiz-Santamaria V, Serra A, Teixido J, Olivé A. Rheumatoid arthritis associatedwith microscopic polyangiitis. Med Clin (Barc) 2000;114:793–4.

[3] Soubrier M, Le Seaux S, Dubost JJ, Mizony MH, Ristori JM, Bussière JL. Rheuma-toid arthritis preceding microscopic polyangitis, report of two cases. Rev MedInterne 2000;21:78–82.

[4] Amano K, Nakabayashi K, Tsuzaka K, Takeuchi T, Koide J, Abe T, et al. A case withrheumatoid arthritis complicated with ANCA-associated vasculitis. Ryumachi1998;38:741–6.

[5] Pankhurst T, Savage CO, Gordon C, Harper L. Malignancy is increased in ANCA-associated vasculitis. Rheumatology (Oxford) 2004;43:1532–5.

[6] Kurzrock R, Cohen PR. Vasculitis and cancer. Clin Dermatol 1993;11:175–87.

[7] Greer JM, Longley S, Edwards NL, Elfenbein GJ, Panush RS. Vasculitis associatedwith malignancy experience with 13 patients and literature review. Medicine(Baltimore) 1988;67:220–30.

[8] Hamidou MA, Derenne S, Audrain MA, Berthelot JM, Boumalassa A, Grolleau JY.Prevalence of rheumatic manifestations and antineutrophil cytoplasmic anti-bodies in haematological malignancies, a prospective study. Rheumatology2000;39:417–20.

[9] Diez-Porres L, Rios-Blanco JJ, Robles-Marhuenda A, Gutierrez Molina M, GilAguado A, Vazquez-Rodriguez JJ. ANCA-associated vasculitis as paraneoplasticsyndrome with colon cancer: a case report. Lupus 2005;14:632–4.

10] Hamidou MA, El Kouri D, Audrain M, Grolleau JY. Systemic antineutrophil cyto-plasmic antibody vasculitis associated with lymphoid neoplasia. Ann RheumDis 2001;60:293–5.

11] Naschitz JE, Rosner I, Rozenbaum M, Elias N, Yeshurun D. Cancer-associatedrheumatic disorders. Semin Arthritis Rheum 1995;24:231–41.

12] Mertz LE, Conn DL. Vasculitis associated with malignancy. Curr Opin Rheumatol1992;4:39–46.

13] Knight A, Askling J, Ekbom A. Cancer incidence in a population based cohort ofpatients with Wegener’s granulomatosis. Int J Cancer 2002;100:82–5.

14] Hayem G, Gomez MJ, Grossin M, Meyer O, Kahn MF. Systemic vasculitis andepithelioma, a report of three cases with a literature review. Rev Rhum Engl Ed1997;64:816–24.

15] Fernandez-Miranda C, Garcia-Marcilla A, Martin M, Gil R, Vanaclocha F, TorresN, et al. Vasculitis associated with a myelodysplastic syndrome: a report of 5cases. Med Clin (Barc) 1994;103:539–42.

16] Hamidou MA, Boumalassa A, Larroche C, El Kouri D, Bletry O, Grolleau JY. Sys-temic medium-sized vessel vasculitis associated with chronic myelomonocyticleukemia. Semin Arthritis Rheum 2001;31:119–26.

17] Reumaux D, Duthilleul P, Roos D. Pathogenesis of diseases associated withantineutrophil cytoplasm antibodies. Hum Immunol 2004;65:1–12.

Gülsüm Emel Pamuk a,∗

Elif Gülsüm Ümit c

Fulya Öz Puyan d

Erman Öztürk a

Muzaffer Demir a

ia Re

c

Letter to the Editor / Leukem

a Division of Hematology, Trakya University Medical Faculty,Edirne, Turkey

b Division of Rheumatology, Trakya University Medical Faculty,

Edirne, Turkey

Department of Internal Medicine, Trakya University Medical Faculty,Edirne, Turkey

d Department of Pathology, Trakya University Medical Faculty,Edirne, Turkey

search 33 (2009) e95–e97 e97

∗ Corresponding author at: Eski Yıldız Cad. Park Apt. No:24,Daire:18, 80700 Besiktas-Istanbul, Turkey.

Tel.: +90 2163477595.

E-mail address: gepamuk@yahoo.com (G.E. Pamuk)

3 December 2008

Available online 23 February 2009