Page 1072 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 60 Myelodysplastic Syndromes 955

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absorption in the small bowel (it is important to note that newer to medical attention. When present, fever is most commonly a sign
forms of gastric bypass, including gastric sleeve procedures and newer of infection, though a small number of patients may run low-grade
iterations of the roux-en-y, maintain small bowel absorption such that fevers in the absence of a discernible infection. Splenomegaly or
patients do not typically develop copper deficiency). Clinically, hepatomegaly are rare and should prompt consideration of either an
patients with copper deficiency develop an anemia that can be nor- alternate diagnosis or an MDS/MPN overlap syndrome.
mocytic or macrocytic and can occasionally be profound. Mild
neutropenia can also be seen, while clinically significant thrombocy-
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topenia is rare. Such patients can also develop neurologic symptoms Dermatologic Manifestations
similar to those seen in vitamin B 12 deficiency, including peripheral
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neuropathy, myelopathy, demyelination, and rarely optic neuritis. Although dermatologic manifestations of MDS are uncommon, a
In the marrow, copper deficiency is classically associated with ring few deserve specific mention. Neutrophilic dermatosis (Sweet syn-
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sideroblasts and erythroid and neutrophil vacuolization. In the drome) is characterized by painful plaques on the face, neck, or
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right clinical setting, negative testing for somatic SF3B1 mutations extremities, often in association with fever and diffuse arthralgias.
in the presence of definite ring sideroblasts should elevate the degree While neutrophilic dermatosis can be seen in any subclass of MDS,
of suspicion. it is classically associated with an impending transformation to AML.
Alcohol is a common cause of hematologic abnormalities, espe- It frequently responds to steroids or dapsone therapy, but may recur
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cially macrocytic anemia, even in the absence of folate or vitamin B 12 as steroids are tapered. Recently, Sweet syndrome in MDS patients
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deficiency. Bone marrow examination often reveals sideroblastic has been associated with heterozygous mutations in MEFV, a gene
changes, and sometimes megaloblastic morphology, but frank dyspla- linked to Mediterranean fever. 285
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sia is uncommon. Patients with borderline marrow findings who Pyoderma gangrenosum (PG) is an ulcerative, necrotic lesion that
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are suspected of significant alcohol intake should be advised to most frequently develops on the extremities. Histologically it is also
completely abstain from drinking (such advice is occasionally heeded), characterized by neutrophilic infiltrates; clinically, it may be associ-
with a repeat marrow examination in 2–3 months. ated with pathergy and frequently develops at the site of recent minor
Other drugs and toxins have also been associated with dysplastic trauma, such as intravenous (IV) catheter insertion sites. PG can be
changes in the marrow. Well-described offenders include valproic associated with a wide range of underlying conditions other than
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acid, mycophenolate mofetil, ganciclovir, alemtuzumab, MDS. A high index of suspicion is necessary to distinguish it from
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nucleoside analogues such as fludarabine and cytarabine, and the necrotizing infections, since treatment of PG involves systemic ste-
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antimetabolites mercaptopurine and methotrexate. These tend to roids, and surgical debridement is contraindicated.
cause macrocytic anemias and can also cause neutropenia and throm- Other dermatologic manifestations of MDS include monocytic
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bocytopenia. On the other hand, isoniazid and chloramphenicol, infiltrates, classically of the gingiva and other mucosal surfaces, a
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and to a lesser extent cycloserine and pyrazinamide, have been process most frequently seen in CMML; the development of a
associated with modest sideroblastic anemia. The anemia associated chloroma or granulocytic sarcoma, which by definition implies pro-
with isoniazid, in particular, can often be reversed with high doses of gression to AML; and petechial lesions, which most frequently develop
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vitamin B 6 (pyridoxine). Chloramphenicol can separately cause an on the lower extremities and imply severe thrombocytopenia.
idiosyncratic pancytopenia that is particularly distinguished by
prominent vacuolization of erythroid precursors. 272
Among infectious agents, HIV infection has specifically been Autoimmune Manifestations
associated with dysplastic changes in the marrow. Patients typically
have hypercellular marrows with evidence of trilineage dysplasia most A percentage of patients with MDS may have overlapping immuno-
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predominant in the erythroid line. The erythroid hematopoiesis logic or rheumatologic features to their disease, which may in part
almost always is megaloblastic, and reticulated fibrosis is often seen arise from the immune dysregulation that occurs during disease
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in bone marrow biopsies. The marrows also often have polyclonal pathogenesis. In a few patients, these may be the presenting
plasma cell expansion, lymphoid aggregates, and granulomas are complaint. Such manifestations can include episodes of seronegative
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often seen. The differential diagnosis of erythrodysplasia in patients oligoarthritis or polyarthritis, cutaneous vasculitis, polymyosi-
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with HIV infection includes the influence of medications, opportu- tis, or autoimmune peripheral neuropathies. Rare patients can
nistic infections, or a direct effect of HIV on the hematopoietic present with a lupus-like syndrome that can include fever, polyar-
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progenitor cells. Since the US Preventive Services Task Force now thralgias, polychondritis, pleuritis, pericarditis, and cytopenias
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recommends a one-time HIV test for all adults, essentially all (including hemolytic anemias). Other autoimmune phenomena have
patients in whom MDS is being considered should be tested to rule also been reported, including mucocutaneous ulcerations, iritis,
out HIV. polymyositis, inflammatory bowel disease, and erythrocyte aplasia.
Other primary hematologic disorders are also on the differential Many of these, which are essentially paraneoplastic syndromes,
diagnosis with MDS. Hypoplastic MDS, for example, can be difficult respond to the initiation of immunosuppressive agents such as
to distinguish from aplastic anemia and in the absence of character- corticosteroids. 292
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istic cytogenetic or genetic abnormalities. Similarly, some patients Some reports have additionally documented cases of patients who
with MDS may have a significant degree of co-existing fibrosis, which were diagnosed with rheumatologic conditions only weeks or months
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can complicate the distinction from a myeloproliferative disorder. before they were found to have MDS, including relapsing polychon-
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Again, genetic analysis may help make this distinction clearer. 278 dritis, polymyalgia rheumatica or temporal arteritis, Raynaud
phenomenon, Sjögren syndrome, and autoimmune glomerulone-
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phritis. However, since some of these conditions are relatively
Signs and Symptoms common themselves, particularly in older populations, whether they
represent a true association with MDS or are merely coincidental
Signs and symptoms of MDS are typically vague. Although some occurrences is not entirely clear.
patients profess to being asymptomatic, fatigue is extremely common,
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as is a sense of general malaise. Rarely, patients may complain of
diffuse arthralgias that can lead to suspicion for an underlying rheu- Objective Findings: Erythroid Lineage
matologic disorder like systemic lupus erythematosus.
Smaller proportions of patients may present with severe or recur- The majority of patients with MDS present with some degree of
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rent infections as a result of immune defects, most commonly anemia, which contributes significantly to fatigue and lethargy, the
neutropenia. Bleeding or easy bruising as a result of thrombocytope- most common presenting complaint. 296,297 The anemia is often
nia or qualitative platelet defects also bring some patients with MDS macrocytic, and the peripheral blood smears of MDS patients