BCG lymphadenitis and failure to thrive in a 9-month-old
Omar is a 9-month-old boy, the third child of first-cousin parents. He received BCG at birth. Since 3 months of age he has had oral thrush, watery diarrhea, and two episodes of pneumonia. His weight is 6.8 kg (birth weight 3.0 kg). Examination shows a left axillary lymph node 3 cm across with a discharging sinus at the BCG scar, hepatosplenomegaly, absent tonsils, and fine crackles at both lung bases. Investigations: lymphocytes 0.8 x 10^9/L (reference 2.5-5.5), CD3-positive cells 12% of lymphocytes, IgG 2.1 g/L, IgA undetectable, IgM 0.3 g/L, HIV antibody negative. Chest radiograph shows diffuse bilateral infiltrates and no visible thymic shadow. He has never attended daycare and his developmental milestones are mildly delayed.
1. What is the unifying diagnosis, and how do the lymphocyte count, thymic shadow, and immunoglobulin pattern support it? Why is the BCG site relevant?
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The unifying diagnosis is severe combined immunodeficiency (SCID), most likely T-B-NK+ or T-B+NK- depending on the genetic defect. The absolute lymphocyte count of 0.8 x 10^9/L is far below the age-related reference and is the first clue; CD3-positive cells at 12% confirm profound T-cell deficiency. The absent thymic shadow, absent tonsils, hypogammaglobulinemia, undetectable IgA, and low IgM fit SCID. HIV is negative, which excludes the main acquired mimic.
The BCG site is central: a discharging axillary node after BCG at birth is BCGitis or BCGosis, a sign that the infant cannot contain a live attenuated vaccine. Live vaccines are contraindicated in SCID because they can disseminate. The chronic thrush and diarrhea reflect impaired T-cell immunity; the pneumonias reflect both T-cell and antibody failure.
Do not stop at recurrent pneumonia. The combination of a live-vaccine complication, absent thymus, lymphopenia, and hypogammaglobulinemia is a pediatric emergency.
2. List the immediate interventions and the specific things that must be avoided. How would you confirm the diagnosis?
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Immediate.
- Admit to a single room with reverse isolation; screen visitors for illness.
- Start IVIG 400-500 mg/kg every 3-4 weeks.
- Give co-trimoxazole prophylaxis for Pneumocystis jirovecii; treat thrush with an antifungal.
- Treat BCGosis with a multidrug regimen active against Mycobacterium bovis: isoniazid, rifampicin, and ethambutol. Pyrazinamide is not useful for BCG. Involve infectious diseases.
- Use only irradiated, leukodepleted, CMV-negative blood products.
- Avoid all live vaccines in the child: BCG, oral polio, rotavirus, MMR, and varicella.
- Avoid steroids and other immunosuppressants unless absolutely necessary.
- Refer urgently for hematopoietic stem cell transplantation, which is the only cure.
Confirmation. Flow cytometry for CD3, CD4, CD8, CD19, CD16/56 and naive T cells; TREC assay; and a genetic panel for SCID genes. Obtain immunology input before giving any vaccine or blood product.
3. What advice would you give about siblings, future pregnancies, and household vaccination?
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Siblings. Screen all siblings with a CBC, lymphocyte subsets, and immunoglobulin levels, even if asymptomatic. Until screened, do not give them live vaccines that could be transmitted to the patient, especially oral polio, rotavirus, and varicella. Inactivated vaccines are safe. If a sibling is also affected, the same isolation and transplant pathway applies.
Future pregnancies. The likely inheritance is autosomal recessive, so the recurrence risk is 25%. If the genetic mutation is identified, offer prenatal diagnosis with chorionic villus sampling and preimplantation genetic testing. Consanguinity counseling should be non-judgmental and include extended family screening.
Household vaccination. Immunocompetent household contacts can receive inactivated vaccines. Live injectable vaccines are generally acceptable, but varicella and rotavirus should be discussed with immunology because of shedding. Avoid oral polio vaccine in the household. The patient should not receive any live vaccine, including BCG revaccination.
Counseling. Explain that the child must avoid crowds and sick contacts, and that early transplant offers the best survival. Provide written emergency instructions and a contact number.