Case Studies

 Case 8.4 Graft-versus-host disease in an infant with severe combined immune deficiency

A 3-month-old boy was admitted to hospital with failure to thrive and a persistent cough. On examination his height and weight were below the third centile. Initial investigations revealed marked anaemia: Hb 50g/l, white-cell count 8.9 x 10⁹/l, platelet count 260 x 10⁹/l. A chest X-ray was reported to be compatible with right lower lobe pneumonia but no organism was identified on blood culture. He was treated empirically with broad spectrum antibiotics but failed to improve.

In view of his anaemia he was transfused with two units of packed red cells. Six days following transfusion he developed a widespread erythematous maculopapular rash and abnormal liver function tests. A skin biopsy showed diffuse vacuolar degeneration of basal epidermal cells with a mononuclear inflammatory cell infiltrate and aberrant expression of HLA-DR on epidermal keratinocytes. These findings were indicative of GVHD and raised the possibility of underlying immunodeficiency in the baby. Subsequent immunological investigations were diagnostic of severe combined immune deficiency (SCID): i.e. marked T- and B-cell lymphopenia and hypogammaglobulinaemia.

In the light of this diagnosis the baby was bronchoscoped and analysis of bronchial secretions revealed Pneumocystis carinii, a common pathogen in babies with defective cellular immunity. The baby was treated aggressively with co-trimoxazole, intravenous immunoglobulin and prophylactic antifungal therapy. Despite his poor outlook it was decided to perform a single haplotype matched bone marrow transplant from his father. Sadly, this was unsuccessful and the baby died 3 days later from overwhelming sepsis. This was not unexpected since transplantation in the face of established GVHD and sepsis often proves difficult. GVHD as a result of the use of non-irradiated blood should not occur now that there is greater awareness of SCID, but is included here to demonstrate the obvious similarity of findings between GVHD due to blood T lymphocytes and bone marrow cells.

While the general principles of bone marrow transplantation for leukaemia and SCID are similar, comparison of this case with Case 8.3 highlights some important differences (Table C8.1).

Table C8.1 Comparison of bone marrow transplantation for primary immune deficiency with BMT for leukaemia.

GVHD, graft-versus-host disease.