A rare mutation causing autosomal dominant STAT1 deficiency in a South African multiplex kindred with disseminated BCG infection.

BACKGROUND: Autosomal dominant signal transducer and activator of transcription 1 (STAT1) deficiency, part of the Mendelian susceptibility to mycobacterial disease (MSMD) group, frequently causes disseminated Bacillus Calmette-Guérin (BCG) infections, but has not been reported from Sub-Saharan Africa (SSA) where routine birth BCG vaccination is practiced. CASE PRESENTATION: Two half-siblings presented five years apart, with multifocal osteomyelitis as the dominant feature of disseminated BCG, which was successfully treated with antimycobacterial therapy. Whole exome sequencing demonstrated a novel heterozygous substitution in the splice site between intron 13 and exon 14 of the STAT1 gene, NM_007315: c.1128-1G>A, in the proband and his mother and was later confirmed in his half-brother. CONCLUSIONS: Children with BCG vaccine complications in SSA should be referred for further investigation and particular consideration of MSMD.

Clinical, Laboratory, and Molecular Findings for 63 Patients With Severe Combined Immunodeficiency: A Decade´s Experience.

BACKGROUND: Severe combined immunodeficiency (SCID) is a life-threatening pediatric disease. We report on the clinical evaluation, immunological assessment, molecular analysis, and outcomes of SCID patients in a tertiary referral center in Iran. METHODS: From January 2006 to December 2015, we performed a prospective cohort study in which initial screening and advanced immunological tests were carried out on patients suspected of having SCID. Genetic analysis was also performed to confirm the diagnosis. RESULTS: A total of 63 patients were diagnosed with SCID (43 male [68.3%]). The median age at onset and diagnosis and diagnostic delay were 40 and 110 and 60 days respectively. A total of 49 patients (77.8%) had a history of BCG vaccination, and of these, one-third experienced BCG-associated complications. The most common clinical manifestations were pneumonia, recurrent oral candidiasis, chronic diarrhea, and failure to thrive. Of the thirteen patients who underwent hematopoietic stem cell transplantation, 8 survived and 5 died before they could receive the transplant. Most patients (34.9%) were classified as having T-B-NK+ SCID and had a mutation in the RAG2 or RAG1 gene. CONCLUSIONS: Autosomal recessive SCID is the most common type in Iranian patients. Providing high-quality training to physicians and patients' families to reduce the diagnostic delay should be prioritized. It is also important to raise awareness of live vaccination and to expand stem cell donor registries to speed up the transplantation process.

Asymptomatic renal BCG granulomatosis: An unusual complication of intravesical BCG therapy for carcinoma urinary bladder.

Bacillus Calmette-Guerin (BCG) is considered the most effective adjunctive treatment available to treat superficial bladder carcinoma. Although BCG is well tolerated by most patients, it may be associated with adverse effects. One of these is BCG granulomas in the kidney. We herein report a case of a 52-year-old patient who, during a surveillance contrast-enhanced computed tomography (CT) scan, was found to have multiple hypodense lesions in the left kidney. Ultrasound-guided biopsy proved it to be BCG granulomas. After 3 months of anti-tubercular treatment, a repeat CT showed complete resolution of the lesions.

The use of natural killer cell activity and PPD test in the prediction of results in intravesical BCG treatment of patients with nonmuscle-invasive bladder cancer.

PURPOSE: To predict the efficacy of intravesical BCG therapy in patients with nonmuscle-invasive bladder tumors (NIBC) by using components of the cellular immune response such as the tuberculin skin test (PPD) and natural killer (NK) activity measurement. METHODS: Ninety-nine patients who were started on intravesical BCG therapy for NIBC were evaluated prospectively. Patients who were included in the intermediate, high, and very high-risk groups according to the EAU NMIBC Scoring System and who had never received intravesical BCG therapy previously were included. The clinical and demographic characteristics of the patients (age, gender, EAU NMBIC risk group, EORTC progression and recurrence scores, CUETO progression and recurrence scores, presence and types of comorbidity) were recorded. NK activity was measured and the PPD test was applied 3 days before the start of intravesical BCG therapy. The results of PPD were measured in millimeters 72 h after the test. RESULTS: PPD values measured before BCG treatment, as an independent variable, were found to be significantly lower in patients with recurrence. A significant correlation was detected between NK activity results obtained before BCG treatment and recurrence after treatment, when the cutoff was 200-500 pg/dl. There was no significant relationship between the time to recurrence and PPD and NKA measurements. CONCLUSION: We conclude that the results of PPD test and NK activity measurement performed before starting intravesical BCG therapy in NIBC may be a marker that can be used to predict the risk of recurrence under treatment.

Suppurative complications following BCG vaccine in 2 Nepalese children.

Background: The Bacillus Calmette-Guérin (BCG) vaccine is one of the most common vaccines administered worldwide and awareness regarding its usual and adverse reactions is important. Local and systemic complications require accurate identification for timely therapy. We hereby report two patients with rare suppurative local complications of BCG. Case presentation: Case 1: A nine-month-old boy presented with swelling over the right deltoid for one month with low-grade fever and purulent discharge for two days. The active discharge occurred from the same site of previous BCG inoculation, the regression of which was achieved conservatively. Case 2: The second case was a 14-month-old boy who presented with a swelling over the lower part of the right axilla for one year, later diagnosed as a tuberculous lymph nodal abscess. Needle aspiration was done and anti-tubercular therapy was started based on positive Gene Xpert reports. Both the cases resolved completely without complications. Conclusion: Pharmacovigilance surveillance of BCG scar reactions and occurrence of suppurative complications should be known by clinicians for correct identification and management.

Urethral fistula and perineal collection during intravesical treatment for non-muscle invasive bladder cancer - A rare complication.

Intravesical Bacillus Calmette-Guérin (BCG) immunotherapy for non-muscle invasive bladder cancer (NMIBC) has been used as a treatment since 1976. It is effective in reducing disease recurrence and progression, with mostly self-limiting or mild side effects. Serious complications are rare and thought to be either related to systemic BCG infection (BCG-osis) or a systemic inflammatory response, and often require systemic anti-tuberculous therapy. We report a rare case of urethral fistulation leading to perineal BCG-abscess during intravesical BCG immunotherapy for high grade bladder cancer. This ultimately required systemic anti-tuberculous therapy and cessation of intravesical BCG treatment.