Journal of Global Infectious Diseases

: 2014  |  Volume : 6  |  Issue : 3  |  Page : 132--134

Disseminated bacillus calmette guerin disease in a twin infant with severe combined immunodeficiency disease

Hema Mittal, MMA Faridi, Pankaj Kumar, Anju Aggarwal 
 Department of Paediatrics, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi, India

Correspondence Address:
Hema Mittal
Department of Paediatrics, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi


Fatal-disseminated Bacillus Calmette Guerin (BCG) disease is well known in infants with severe combined immunodeficiency after BCG vaccination. We report a 7 month male infant delivered as a product of in vitro fertilization and twin gestation that presented with fever, cough and multiple nodular skin lesions. A biopsy of skin lesions revealed the presence of acid fast bacilli. Mycobacterium bovis infection was confirmed by polymerase chain reaction (PCR) and molecular studies. Immunological profile confirmed the diagnosis of severe combined immunodeficiency. Only few reports of similar case exist in the literature.

How to cite this article:
Mittal H, Faridi M, Kumar P, Aggarwal A. Disseminated bacillus calmette guerin disease in a twin infant with severe combined immunodeficiency disease.J Global Infect Dis 2014;6:132-134

How to cite this URL:
Mittal H, Faridi M, Kumar P, Aggarwal A. Disseminated bacillus calmette guerin disease in a twin infant with severe combined immunodeficiency disease. J Global Infect Dis [serial online] 2014 [cited 2021 Jan 21 ];6:132-134
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Bacille Calmette Guerin (BCG) vaccination is recommended under Expanded Program for Immunization by World Health Organization at birth in developing countries. It is a live vaccine which is contraindicated in immunodeficiency states like acquired immunodeficiency syndrome (AIDS) and severe combined immunodeficiency disease (SCID). BCG vaccination in children with SCID carries higher risk of fatal disseminated BCG disease. [1],[2] Skin manifestations in disseminated BCG lesions in infants with SCID have been reported in the past. [3],[4] We report disseminated BCG vaccine disease with skin lesions in one of the twins suffering from SCID.


A 7-month-old first born male twin infant, adopted by his uncle, presented with loose stools for 3 days in a private clinic. Child was started on intravenous fluids and other supportive treatment. After 48 hours loose stools improved but he developed fever, cough and fast breathing. A diagnosis of viral or nosocomial infection was made and child was transferred to pediatric intensive care unit. Unsatisfied parents took the child and left against medical advice. The child was brought back to the clinic after 3 days with history of fever, cough, fast breathing and skin rashes. There was no history of bleeding from any site. Past medical history revealed frequent infections since birth, including episode of documented rota virus diarrhea, bronchiolitis and oral thrush. He was an adopted child from his paternal uncle and product of in vitro fertilization and twin gestation (first twin). The infant was on formula feeds and few sessions of breastfeeding daily by his biological mother since birth who was living in the same premises. Infant received Hepatitis B, BCG and oral polio vaccine (OPV) vaccine at birth followed by three doses of DPT, Hepatitis B and OPV at 6, 10 and 14 weeks age. On examination child had fever (102°F), respiratory rate 56 breaths per minute, mild pallor, oral thrush and red to purple, papulo-nodular, fixed and non-itching subcutaneous lesions, 0.5-2 cm in size, over neck, back and abdomen [Figure 1]a. Chest examination revealed bilateral diffuse crepitations and rhonchi. Chest X-ray showed right upper zone consolidation. A diagnosis of pneumonia was made. The differential diagnosis for the rash was drug reaction, panniculitis and vitamin K-dependent bleeding (VKDB) from prolonged use of broad spectrum antibiotics. Child was started on injectable ceftriaxone and vancomycin. A skin biopsy was taken from three sites. An abnormal prothrombin time (PT) 16 sec (12 sec control) suggested VKDB and was treated with Vitamin K (5 mg intravenously for 3 days). Investigations showed anemia (Hb 10.0 g/dl), positive C-reactive protein (8 mg/dl), and normal total leukocyte count (6200 cells/mm 3 : Neutophils 42%, lymphocytes 48%, monocytes 9%, eosinophils 1%, basophils 0), platelets (280 × 10 3 /mm 3 ) and sterile blood and urine cultures. In view of non-improvement and persistent pneumonitis after 72 hours of intravenous antibiotics and supportive treatment (repeat chest X-Ray revealed bilateral infiltrates) infant was investigated for tuberculosis. Mantoux test was non-reactive and gastric aspirates were negative for acid fast bacilli. Ultrasound abdomen was essentially normal except mild hepatomegaly. A skin biopsy showed sheets of macrophages with neutrophilic micro abscess; species stain was acid fast bacilli (AFB) strongly positive (6+) with infiltrate of macrophages laden with bacilli (globii) [Figure 1]b. A diagnosis of disseminated tuberculosis was made and antitubercular therapy (isoniazid, rifampicin, pyrazinamide and ethambutol) with prednisolone (2 mg/kg) was started.{Figure 1}

In view of non-resolving pneumonia, lymphopenia (2976/mm 3 ) and history of recurrent past infections immunodeficiency was suspected. HIV testing of mother and child was negative. An immunological profile showed low immunoglobulins, normal B lymphocytes and decreased T cells and natural killer (NK) cell counts [Table 1] suggestive of SCID. A skin biopsy was sent for culture and polymerase chain reaction (PCR) analysis. Culture Rapid (automated Bact Alert 3 D system; Biomerieux, France) after 3 weeks was positive for acid fast bacilli and immune chromatographic test MPT64 implying Mycobacterium tuberculosis complex (MTB) which was further confirmed by Oligonucleotide probe liquid hybridization protection assay (Accuprobe, Genprobe, SA). Pyrazinamidase screening results showed resistance, and further molecular typing and biochemical tests confirmed Mycobacterium bovis. Thus, diagnosis of disseminated BCG disease with combined severe immunodeficiency was made. [5],[6] The infant deteriorated and on day 10 of admission, was put on mechanical ventilator and died after 5 days. Family was counseled and the mother and another twin offered to be screened for immunodeficiency. There was no history of recurrent infections and failure to thrive in parents or other twin. Second male twin is alive and healthy till date. Immunological profile of other twin showed normal B, T and NK cell functions. However, parents refused for any laboratory investigations. The facial features and blood groups of both the twins were different suggesting dizygosity.{Table 1}


Disseminated BCG disease is a rare complication (approximately 1/million) of BCG vaccination in immunocompetent children. [7] However, children with immunodeficiency have higher risk of disseminated BCG. Talbot et al. and Loette et al. have reported the occurrence of disseminated BCG disease in 86% and 100% children with immune defects, respectively. [1],[8] Disseminated BCG disease has high mortality in infants with SCID. [1],[2] Disseminated BCG disease generally manifests as fever, malnutrition, and pneumonitis 3-6 months after receiving BCG vaccination. Hepatosplenomegaly, lymphadenopathy, osteomyelitis, renal disease, meningitis have also been reported. [1] Skin manifestations like subcutaneous nodules, rash, ulcers, and erythema in SCID infants with disseminated BCG disease have been reported by some authors. [3],[4] More than 30 genetic defects are known in SCID which may be inherited as X-linked recessive or autosomal recessive. X-linked SCID in 50% and adenosine deaminase (ADA) deficiency (autosomal recessive) in 15-20% cases of SCID are most common disorders. Unless treated SCID is uniformly fatal in first 2 years of life. Disseminated BCG infection also carries very high fatality (1) in children with SCID. Definitive therapy of SCID is hematopoietic stem cell transplantation with up to 95% success. [9] Prenatal diagnosis is possible by mutation analysis. Routine newborn screening by T-cell receptor excision circles (TRECs) by PCR, using DNA extracted from newborn dried blood spots (Guthrie cards), has been recently implemented in Wisconsin (USA). [10] As routine BCG vaccination is recommended at birth to all newborns in most developing countries and children with immunodeficiency are symptomatic afterwards, most of these children remain at risk of fatal disseminated BCG disease.


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