Symptoms and Signs of Myelodysplastic Syndromes 3

Symptoms and Signs of Myelodysplastic Syndromes

Patients can be asymptomatic or, if anemia is more severe, can have pallor, weakness, loss of a sense of well being, and exertional dyspnea.14,93,94 A small proportion of patients have infections related to severe neutropenia or neutrophil dysfunction, or hemorrhage related to severe thrombocytopenia or platelet dysfunction at the time of diagnosis. Patients with severe depressions of neutrophil and platelet counts at diagnosis usually have oligoblastic myelogenous leukemia. Rarely, patients have fever unrelated to infection.95 Arthralgia is the initial complaint in some patients.84 The presentation, infrequently, can mimic a connective tissue disease.96,97 Hepatomegaly or splenomegaly occurs in approximately 5 or 10 percent of patients, respectively.

Special Clinical Features of Myelodysplastic Syndromes

Diabetes Insipidus of Myelodysplastic Syndromes

Patients with an indolent phase (oligoblastic myelogenous leukemia) prior to overt AML may develop diabetes insipidus. Hypothalamic involvement can lead to polyuria, polydipsia, and decreased libido. Hypothalamic-posterior hypophysis insufficiency in clonal myeloid states is associated with monosomy 7 in hematopoietic cells.98,99 Hypodipsia can occur with extensive hypothalamic involvement. The syndrome lacks the signs of thirst, polyuria, and polydipsia because signals transmitted by the thirst center to the cerebral cortex are blocked.99

Neutrophilic Dermatosis of Myelodysplastic Syndromes

Acute neutrophilic dermatosis (Sweet disease) is an acute febrile illness characterized by erythematous patches on the arms, face, and legs that progress to painful brown plaques. The plaques may ulcerate and produce large necrotizing skin lesions. The histopathology of the skin is that of a dense dermal neutrophilic infiltrate.100,101 The syndrome, which occurs principally in middle-aged women, lasts for 6 to 10 weeks, often is associated with blood neutrophilia, and may recur. At least 10 percent of patients with Sweet disease develop AML or another clonal myeloid disease. Occasional cases have been associated with monocytosis or cytogenic abnormalities in marrow cells prior to AML onset. Granulocyte colony-stimulating factor (G-CSF) and all trans-retinoic acid (ATRA) administration has been followed by Sweet disease in some cases.101 Other dermatopathic conditions also have been associated with clonal myeloid diseases.102

Inflammatory Syndromes of Myelodysplastic Syndromes

Immune or inflammatory syndromes may be seen in as many as 10 percent of patients. A symptom complex that mimics systemic lupus erythematosus; fever, pleurisy, symmetric arthritis, plasma antinuclear antibody, and pancytopenia with a hyperplastic marrow) may precede AML.96 Several patients with signs of systemic lupus erythematosus and the lupus erythematosus cell phenomenon were reported in a review of the clonal myeloid syndromes.96,103 Behçet disease, glomerulonephritis, seronegative arthritis, systemic vasculitis, polychondritis, polyneuropathy, panniculitis, and inflammatory bowel disease also have been associated with clonal myeloid disorders.96,97,104–109

Other Cancers of Myelodysplastic Syndromes

The incidence of other cancers may be higher in subjects with myelodysplastic diseases.