Infection

Viral infection

As with idiosyncratic reaction to drugs, hypoplasia occurs in only a miniscule proportion of those exposed. However, viral infection is probably an under-diagnosed cause: EBV for example may be demonstrable in patients without the typical clinical features of infective mononucleosis and acyclovir may produce hematologic improvement when a virus etiology cannot be proven. The destructive effect of virus may be due to direct action or an immune effect such as T-lymphocyte mediated suppression.

The best-known association is with viral hepatitis - usually non-A, -B, -C. Hypoplasia is usually severe, though the preceding hepatitis may not be and manifests at a mean of 9-10 weeks after onset of hepatitis.

Hypoplasia occurs in isolated instances of infection with EBV, HIV, Varicella, CMV, dengue-type viruses, measles, mumps and parvovirus. Hypoplasia is more likely if there is associated immunodeficiency either drug-induced or natural, eg. EBV in x-linked lymphoproliferative disorder. Although the effect of parvovirus is ordinarily restricted to the erythron, panhypoplasia occasionally occurs in apparently normal persons.

Transient hypoplasia may occur in rickettsial infection, e.g. Q fever and ehrlichiosis.

Genetic syndromes and panhypoplasia

Fanconi's syndrome

Diagnosis is most reliably made by quantitation of chromosomal breaks (cultured blood lymphocytes) induced by the DNA cross-linking agent, diepoxybutane (DEB, Auerbach et al 1989). Abnormal fragility appears to be specific for Fanconi's anemia and is detectable from birth and before onset of cytopenias. A scoring system for diagnosis, using other characteristics, has been devised.

Approximately 7% of patients do not have malformations. The DEB procedure is therefore recommended for all cases of panhypoplasia, whether associated with malformations or not. The DEB procedure does not reliably detect the carrier state (autosomal recessive). Sibs and parents may share some of the somatic anomalies but do not have blood changes. Heterogeneity is in part explicable by the existence of at least 2 genes for the disorder (chromosome 9 and 20).

Blood abnormalities are rare before 18 months and may not manifest till about 20 years. Average age at onset of pancytopenia is about 6 and 1/2 years for boys and about 8 and 1/2 years for girls. Thrombocytopenia is usually the first sign and may be misdiagnosed as idiopathic if the association with somatic anomalies is not recognized; granulocytopenia and then anemia follow, evolving over months to years. Fetal features e.g. macrocytosis and increased HbF (heterogeneous distribution and i antigen are common, even before onset of anemia.

Dyserythropoiesis is common, with megaloblastosis, internuclear bridges, karyorrhexis and defective hemoglobinization. In the pre-symptomatic period, the marrow may appear normal or show hyperplasia.

There is a risk (about 20%) of malignancy, especially AML-M4 and squamous cell carcinoma. Malignancy is occasionally the presenting feature.

Dyskeratosis congenita

Ectodermal dysplasia is characteristic - in skin, nails and teeth and in hair (loss or premature graying); leukoplakia of squamous surfaces may produce stricture of hollow viscera (e.g. oesophagus) and is a risk (about 10%) for malignancy. Growth retraction is common.

Table 4 : Genetic syndromes and marrow panhypoplasia

• DNA repair detect
  
  • Fanconi
  • Dyskeratosis congenita
    
    
• Pancreas-marrow syndromes
  
  • Shwachman
  • Pearson
  • Atypical cystic fibrosis
    
    
• Others
  
• Defective cellular uptake of folate
  
• Aplasia preceded by congenital amegakaryocytosis
  
  

Last created on 22-01-2002
Last updated on 01-07-2006