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Systemic vasculitis and myelodysplastic syndromes. A report of two cases

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Vol. 40, No. 1, January 1997, pp 179-182
0 1997, American College of Rheumatology
A Report of Two Cases
Two cases of systemic vasculitis associated with
myelodysplastic syndromes are reported. Vasculitis may
develop either before or after the diagnosis of a hematologic disorder, and it responds to treatment with
high-dose corticosteroids.
Myelodysplasticsyndromes (MDS) are characterized by cytopenia and histologic features of hematopoietic dysplasia. The natural history of MDS varies widely,
ranging from chronic anemia with a low propensity for
leukemic conversion to disorders characterized by profound disturbances in blood cell production with a high
risk of progression to acute leukemia or bone marrow
failure. These syndromes are classified according to
morphologic features and bone marrow blast cell counts
(1). Some reports have suggested that MDS may be
accompanied by immune disorders (2).
Few cases of MDS associated with cutaneous
vasculitides have been previously reported (3-6). We
describe 2 patients with systemic vasculitis. One had
refractory anemia with excess blasts and the other had
refractory anemia, both of which are subtypes of MDS (1).
Patient 1. In June 1992, a 68-year-old man developed
pruritic erythematous papules on his back, shoulders, neck,
Bruno Philippe, MD: Pneumologie Hapita1 Foch, Suresnes et
Universite Paris-Ouest, Suresnes, and Hapita1 Necker, Paris, France;
Louis-Jean Couderc, MD, Bernard Epardeau, MD, Olivier Bletry,
MD, Isabelle Caubarrere, MD: HBpital Foch, Suresnes et Universite
Paris-Ouest, Suresnes, France; Dorninique Droz, MD, Georges
Choukroun, MD, Bruno Varet, MD, Olivier Hermine, MD: Hapita1
Necker, Paris, France; Fredtric Charlotte, MD: Hopital La PitiC
Salpttritre, Paris, France.
Address reprint requests to Louis-Jean Couderc, MD, Service
de Pneumologie, Hapita1 Foch, 40 rue Worth, 92150 Suresnes, France.
Submitted for publication February 26, 1996; accepted in
revised form July 15, 1996.
and head. Skin biopsy revealed a perivascular cellular infiltrate
made up of small lymphocytes and histiocytes in the dermis,
with infiltration of the capillary vessel walls without leukocytoclasia. Direct immunofluorescence showed no immunoglobulin or complement deposition.
Laboratory tests showed mild anemia, with a hemoglobin level of 93 gmiliter. The white blood cell (WBC) count was
3.08 X lOY/liter,with 37% neutrophils, 56% lymphocytes, 4%
monocytes, and 7% eosinophils, and the platelet count was 123
X 10’iliter. Bone marrow aspiration showed normal cellularity,
with reduced segmentation and granulation of granulocytes
and 5% of blasts, consistent with refractory anemia with excess
blasts (1). No cytogenetic abnormality was detected. The
patient received red blood cell transfusions and prednisolone,
40 mg/day, with the dosage tapered over 15 days. The cutaneous lesions regressed within 3 days.
One year later, the patient complained of an enlarged
right testis and blood in his urine. No cutaneous lesion was
identified. Biopsy of the epididymis showed characteristic
interstitial lesions of vasculitis. Larger arteries showed fibrinoid necrotic foci of the vessel wall and parietal thrombosis. The
vessel wall was infiltrated with polymorphic inflammatory cells
including polymorphonuclear neutrophils, with leukocytoclasia
(Figure 1).At this time, his serum creatinine level rose to 1,045
A transjugular renal biopsy specimen revealed extensive polymorphic interstitial cellular infiltration composed of
lymphocytes,plasma cells, polymorphonuclear cells, and eosinophils, as well as interstitial hemorrhage in the medulla. The
arterioles and arteries were normal, the glomeruli were ischemic, and epithelial cell necrosis was observed in the tubules.
Direct immunofluorescence revealed IgA-containing interstitial plasma cells and C3 deposits in the vessels.
No antibodies to human immunodeficiency virus, human T lymphotropic virus type I, hepatitis A, B, and C viruses,
cytomegalovirus, Toxoplasma, or Mycoplasma pneumoniae
were detected. The results of immunologic tests for antinuclear
antibodies, rheumatoid factor, cryoglobulins, immunoglobulin
levels, Coombs’ test, total hemolytic complement, C3, C4,
antineutrophil cytoplasmic antibodies (ANCA), and antiglomerular basement membrane antibodies were negative or
normal. No monoclonal protein was detected by serum
Figure 1. Epididymis biopsy of patient 1, showing fibrinoid necrosis
and a prominent neutrophil infiltrate, with leukocytoclasia (arrows) of
the arterial wall. M = media; L = lumen (hematoxylin and eosin
stained, original magnification X 160).
The patient underwent 4 hemodialysis sessions, and he
was treated with prednisone, 60 mg/day. Within 1 week, the
testis appeared normal. Bone marrow cytology did not show a
progression of the refractory anemia with excess blasts. The
first year of followup was marked by several relapses of the
cutaneous vasculitis after the prednisone dosage had been
tapered to 30 mg/day for 6 months. Danazol, 600 mg/day, was
begun, which made it possible to decrease the corticosteroids
to 20 mg/day. The followup course was unremarkable over the
next 2 years.
Patient 2. A 27-year-old man complained of dyspnea of
3 years' duration. In 1993, a chest radiograph and thoracic
computed tomography scan showed diffuse bilateral interstitial
infiltrates. Bronchoalveolar lavage showed a total of 144 X
103/mlalveolar cells, with 28% lymphocytes, 21% neutrophils,
1% eosinophils, and 50% alveolar macrophages (60% siderophages). Findings of special stains and cultures for pathogens were negative. Open lung biopsy showed neutrophil
polymorphonuclear foci and small lymphocytes, with destruction of small vessel walls (Figure 2).
The patient's creatinine level and urinary sediment
were normal. Results of the same immunologic and virologic
tests as in patient 1 were negative or normal. His hemoglobin
level was 60 gm/liter, the WBC count was 3.5 X 109/1iter,with
43% neutrophils, 40% lymphocytes, 8% eosinophils, and 6%
monocytes, and the platelet count was 125 X lO'/liter. Fetal
hemoglobin was increased to 8.1% (normal <2%).
Bone marrow aspirate was normocellular; granulopoiesis was hypoplastic, with a reduction in segmentation and
granulation of the granulocytes but no excess blasts. The bone
marrow progenitor culture at day 10 showed virtually no
granulocyte-macrophage colony-stimulating factor and 24
clusters/lO' mononuclear cells, consistent with a diagnosis of
refractory anemia (1). Cytogenetic analysis gave normal
Fifteen days after the open lung biopsy, the patient's
Figure 2. Lung biopsy of patient 2, showing infiltration of small vessel
walls by small lymphocytes and some polymorphonuclear leukocytes
(hematoxylin and eosin stained, original magnification X 160).
dyspnea worsened. His temperature was 39"C, and a chest
radiograph showed diffuse bilateral alveolar and interstitial
opacities (Figure 3). Arterial blood gases obtained while the
patient was breathing room air showed mild hypoxemia (Pao,
Figure 3. Chest radiograph of patient 2, showing diffuse alveolar and
interstitial opacities bilaterally.
70 mm Hg, Paco, 35 mm Hg). A blood transfusion was not
done because of the patient’s religious beliefs. He was given
500 mg of methylprednisolone per day, intravenously, for 2
days, then oral prednisone 50 mg/day. His fever and dyspnea
disappeared, and the Pao, increased to 97 mm Hg, within 48
hours. Simultaneously, the size of the pulmonary opacity
decreased. He was discharged from the hospital on a regimen
of 40 mg of prednisone daily, and was lost to followup.
Vasculitis associated with a malignancy is a well
known event which occurs more often in association with
hematologic diseases (particularly hairy cell leukemia)
than with solid neoplasms (3,7). These vasculitides usually affect the skin and joints, but rarely other organs
(3-6). Vasculitis may develop either before or after the
hematologic disorder is diagnosed. There have been
only a few reports of suspected systemic vasculitis with
lung involvement or the presence of ANCA in MDS
patients (8-10).
The clinical and histologic profile of patient 1was
consistent with a diagnosis of macroscopic periarteritis
nodosa, which has never been reported in MDS (8).
Such a pathologic aspect has been described only in
hairy cell leukemia (9). Consistent with this diagnosis,
our patient did not have ANCA. The second patient
presented with alveolar hemorrhage complicating the
pulmonary vasculitis with no systemic involvement, and
no ANCA was demonstrated. A similar vasculitis limited
to the lungs has been recently reported (11).
The mechanisms underlying vasculitis remain unknown. One hypothesis would be an activation of B cells
and the synthesis of organ-specific and non-organspecific autoantibodies, which in 1 study (2), were
present in 15 of 67 patients tested (22%). However,
Savige et a1 (12) could not demonstrate a consistent
relationship between the presence of ANCA and MDSassociated vasculitis, since only 1 of 25 patients with
MDS was positive for ANCA. Another explanation has
been suggested for the potential role of either autoreactive T cells or autoantibodies which may sometimes
occur in MDS (2). Another possibility would be that
immune complexes are involved. Indeed, macrophage
function is severely impaired, which results in decreased
immune complex clearance (13). In addition, neutrophil
chemotaxis could be accompanied by oxide anion hyperproduction, which implies organ injury, such as that
described in Sweet’s syndrome with lung involvement
(14). Finally, another hypothesis may be that bone
marrow changes play a significant role in the etiology of
vasculitis (10).
Some authors have reported a worse prognosis
for MDS associated with vasculitis (4). In most cases,
vasculitis responded dramatically to steroids and did not
usually require the addition of other immunosuppressive
therapies, which may worsen MDS-related cytopenia
(12,15). Consistent with these findings, and despite
severe and life-threatening systemic involvement, our 2
patients responded to corticosteroid treatment. However, the skin involvement in patient l recurred when
the corticosteroid dosage was tapered. We therefore
successfully used danazol as an immunomodulating
agent (16) to prevent the recurrence of systemic involvement. In our 2 patients, treatment of the vasculitis had
no effect on the course of the MDS.
In conclusion, our 2 patients showed clear biopsy
evidence of lung and testicle involvement by vasculitis.
Therefore, patients with apparently idiopathic systemic
vasculitis should be evaluated for underlying MDS as
well as for other well-known causes. Furthermore, in the
2 cases reported here, systemic vasculitis did not seem to
be associated with a worse prognosis and responsed to
high-dose corticosteroids.
The authors thank Ms G. Flohic for secretarial
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