Severe combined immunodeficiency with thrombocytopenia and disseminated mycobacteriosis

Background: Severe Combined Immunodeficiency (SCID) is the most severe form of primary immunodeficiency and it’s characterized by absence of T-cell mediated immunity and impaired B-cell function. Early onset and severe infectious complications are the main symptoms. Bone marrow transplant is one curative treatment available and should be performed as soon as possible in the course of the disease.

Methods: Retrospectively reviewed laboratory and clinical data.

Results: JPOL, 2 year-old male, born to non-consanguineous parents, was a previously healthy boy until 14 months of age when he presented with 5 days of fever and pancytopenia. He was admitted for 10 days when fever and hematological abnormalities resolved after antibiotic use. Blood cultures and serum titers for the most prevalent viruses were negative. At 1 1/2 years he started to present mild diarrhea, perineal dermatitis and abdominal distension with splenomegaly. In less than 24 hours the perineal hyperemia evolved to an extensive necrotic ulcer. The patient was admitted to the intensive care unit with septic shock followed by cardio respiratory arrest. He developed severe neutropenia, hemolytic anemia (direct Coombs positive) and autoimmune thrombocytopenia (anti-platelet IgM positive) requiring several blood product infusions (more than 30). At the same time, he started to present new cutaneous lesions over the scalp, left hand and feet. He was also submitted to a colostomy for better perineal healing. All blood, urine and skin biopsy cultures were negative. The histopathological exam from the perineal ulcer was compatible with Pyoderma Gangrenosum and he was started on corticosteroids when the lesions improved quickly. IgA, IgG and IgE levels were very low but IgM was extremely high (more than 4,000 mg/dL) so he was started on intravenous immunoglobulin. Lymphocyte immunophenotyping showed a normal number of CD3⁺ T lymphocytes (3,290/mm³) however there were no naïve CD4⁺ or CD8⁺ T cells. B cells were absent (4.5/mm³) while NK cell number was increased (2,354/mm³). Diagnosis of T-B-NK+ SCID was made. Bone Marrow Immunohistochemistry was compatible with Mycobacteriosis and CNS MRI showed multiple granuloma formation. Patient had been vaccinated twice with BCG, at birth and at 9 months (because of no BCG scar formation). Empirical therapy for Mycobacterium bovis was initiated.

Conclusions: T-B-NK+SCID patients can produce autoantibodies and high IgM suggesting the presence of abnormal clones. Early vaccination with a live microorganism (BCG) poses a great risk to these patients.