a SciTechnol journal Case Report Zahid et al., J Immunodeic Disor 2014, 3:1 http://dx.doi.org/10.4172/2324-853X.1000109 Journal of Immunodeiciency & Disorders All articles published in Journal of Immunodeiciency & Disorders are the property of SciTechnol, and is protected by copyright laws. Copyright © 2014, SciTechnol, All Rights Reserved. International Publisher of Science, Technology and Medicine Recurrent Salmonellosis in a Child with Complete IL-12Rβ1 Deiciency Mohammad Faizan Zahid 1 , Syed Asad Ali 2 , Fyezah Jehan 2 , Abdul Gaffar Billo 2 , Jean-Laurent Casanova 3,4,5 , Jacinta Bustamante 4,5,6 , Stephanie Boisson-Dupuis 3,4,5 and Fatima Mir 2 * Abstract A 3 year old boy presented with fever, abdominal pain and cervical lymphadenopathy. He had previously been treated empirically with anti-tuberculous therapy twice, at age 9 months and 27 months, for peripheral lymphadenopathy. An older sibling died of suspected tuberculous meningitis. Mantoux test was normal. Bone marrow and lymph node biopsy ruled out lymphoma and absolute neutrophil and lymphocyte counts were normal. Blood and lymph node cultures were positive for Salmonella typhi. The child’s symptoms resolved with IV ceftriaxone and he was discharged. Over the next 2 years, the child was admitted every 2-3 months for culture positive S. typhi bacteremia with complaints of fever, abdominal distention and dysentery. HIV workup was negative. A prolonged course of probenicid and high dose amoxicillin increased interval between episodes to 4-5 months only. Cholecystectomy was debated and deferred due to suspicion of immunodeiciency. Blood samples from patient and parents were sent to France for workup and IL-12Rβ1 deiciency was found. Parental counseling and subsequent patient management remained dificult in view of inancial constraints and outstation residence of family. At age 7 years, the child presented with small bowel obstruction. He was managed conservatively with antibiotics, IV luids and blood transfusions, but eventually succumbed to endotoxic shock. This case highlights the importance of considering IL-12Rβ1 deiciency in children with repeated salmonellosis, a diagnosis which precludes intensive and aggressive monitoring and management of the patient in scenarios where bone marrow transplants are not feasible. Introduction Interleukin-12 (IL-12), an immune-modulating cytokine produced by activated antigen presenting cells (macrophages and dendritic cells) plays an important role in combating infections with intracellular organisms. It induces interferon gamma (IFN-γ) production in T and Natural killer (NK) cells and promotes T helper cell (T H cells) activity. In children with mutations in the interleukin-12 receptor β1 (IL-12Rβ1) gene, lymphocytes have an impaired response to IL-12 and display an impaired production of IFN-γ [1]. hese patients are extremely susceptible to infections with mycobacteria *Corresponding author: Fatima Mir, Department of Pediatrics and Child Health, Aga Khan University, Stadium Road, PO Box 3500, Karachi 74800, Pakistan, Tel: 9221-4864955; Fax: 9221-493-4294; E-mail: fatima.mir@aku.edu Received: March 24, 2014 Accepted: May 28, 2014 Published: June 04, 2014 (even poorly virulent Bacillus Calmette–Guérin (BCG) vaccines and environmental nontuberculous mycobacteria) and Salmonella species [2]. Organisms other than intracellular pathogens rarely cause clinical disease in such patients. hough most reports so far show favorable survival, we report the case of a child with IL-12Rβ1 deiciency and recurrent salmonella bacteremia who eventually succumbed to toxic mega-colon and septic shock. Case Summary A 3 years old male child presented with intermittent fever for one and a half years associated with lympho-nodular swellings (cervical), abdominal pain, blood in stool and intermittent rash on face and scalp. Physical examination revealed tachycardia (120 beats per minute), generalized lymphadenopathy, peripheral edema and tinea faciei and capitis. In past medical history, generalized lymphadenopathy and intermittent fever had been noticed irst at age 9 months. He had received an empiric anti-tuberculosis therapy (ATT) regimen twice, once at the age of 9 months and later at the age of 27 months.As per parental recall, he had received BCG vaccine at birth, Hepatitis B, DPT and OPV at 6, 10 and 14 weeks and measles vaccine at 9 months as per national expanded program on immunization (EPI) schedule from Pakistan. BCG scar was not present. he parents had a consanguineous marriage. Of three siblings, two were living. he oldest, a 12 year old brother was well, the second, a 9 year old sister was underweight with conductive deafness due to bilateral chronic suppurative otitis media (CSOM). he third sibling had succumbed to a fatal case of meningitis a year back at age 4 years (suspicion of TB meningitis was solely based on lymphocytic pleocytosis alone in CSF). his child had also had recurrent episodes of blood in stool and a history suggestive of scrofula at 3 years of age. here was no history of contact with an adult with Tuberculosis. All siblings excluding the oldest had received at least two empiric 3 drug ATT regimens for 6-9 months due to generalized lymphadenopathy. All children had received BCG vaccination at birth as per EPI schedule. Initial diferentials at the time of presentation included miliary tuberculosis, lymphoma and primary immunodeiciency syndrome. Laboratory investigations showed borderline Mantoux test (10mm), normal tumor lysis workup (serum electrolytes, BUN, creatinine, phosphate, uric acid and lactate dehydrogenase) and normal immune workup (immunoglobulin levels, Nitrobluetetrazolium test, CD4/ CD8 cell ratio and HIV antibody titers). Complete blood count (CBC) showed neutrophilia. Remaining investigations, which included clotting proile, liver function tests (LFTs) and electrolytes were within normal limits. Abdominal ultrasound and chest x-ray showed enlarged para- aortic, mesenteric and hilar lymph nodes. Lymph node biopsy done in his local province was reviewed. Histopathology showed hemophagocytic lymphohistiocytosis (HLH). his was attributed to be infection-associated. Mycobacterial infection was suspected but empiric regimens were deferred. he child returned to the hospital ater a month with high grade fever and discharging, ulcerated pre-auricular and submandibular