Child ; Humans ; Granulomatous Disease, Chronic/complications* ; Pneumonia

Summary Sporotrichosis is a rare and chronic granulomatous subcutaneous mycotic infection caused by a dimorphic fungus, Sporothrix schenckii. We describe a patient with disseminated cutaneous sporotrichosis who was later diagnosed with myeloproliferative neoplasm and discuss the challenges and importance in diagnosing this rare condition.
Sporotrichosis ; Granulomatous Disease, Chronic ; Myeloproliferative Disorders

PURPOSE: While there is an urgent need for diagnosis and therapeutic intervention in patients with primary immunodeficiency diseases (PIDs), current genetic tests have drawbacks. We retrospectively reviewed the usefulness of flow cytometry (FCM) as a quick tool for immunophenotyping and functional assays in patients suspected to have PIDs at a single tertiary care institute.METHODS: Between January 2001 and June 2018, patients suspected of having PIDs were subjected to FCM tests, including lymphocyte subset analysis, detection of surface- or intracellular-target proteins, and functional analysis of immune cells, at Samsung Medical Center, Seoul, Korea. The genetic diagnosis was performed using Sanger or diagnostic exome sequencing.RESULTS: Of 60 patients diagnosed with definite or probable PID according to the European Society of Immune Deficiencies criteria, 24 patients were provided with useful information about immunological dysfunction after initial FCM testing. In 10 patients, the PID diagnosis was based on abnormal findings in FCM testing without genetic tests. The FCM findings provided strong evidence for the diagnosis of severe combined immunodeficiency (n = 6), X-linked chronic granulomatous diseases (CGD) (n = 6), leukocyte adhesion deficiency type 1 (n = 3), X-linked agammaglobulinemia (n = 11), autoimmune lymphoproliferative syndrome-FASLG (n = 1), and familial hemophagocytic lymphohistiocytosis type 2 (n = 1), and probable evidence for autosomal recessive-CGD (n = 2), autosomal dominant-hyper-immunoglobulin E (IgE)-syndrome (n = 1), and STAT1 gain-of-function mutation (n = 1). In PIDs derived from PIK3CD (n = 2), LRBA (n = 2), and CTLA4 mutations (n = 3), the FCM test provided useful evidence of immune abnormalities and a tool for treatment monitoring.CONCLUSIONS: The initial application of FCM, particularly with known protein targets on immune cells, would facilitate the timely diagnosis of PIDs and thus would support clinical decisions and improve the clinical outcome.
Agammaglobulinemia ; Diagnosis ; Exome ; Flow Cytometry ; Genetic Testing ; Granulomatous Disease, Chronic ; Humans ; Immunophenotyping ; Korea ; Leukocytes ; Lymphocyte Subsets ; Lymphohistiocytosis, Hemophagocytic ; Phenotype ; Retrospective Studies ; Seoul ; Severe Combined Immunodeficiency ; Tertiary Healthcare

OBJECTIVE: To investigate the clinical efficacy of haploid hematopoietic stem cells (haplo-HSC) combined with third-party umbilical cord blood (tpCB) transplantation in the treatment of X-linked chronic granulomatous disease (X-CGD). METHODS: The clinical data of 26 boys with X-CGD were retrospectively analyzed who were admitted to the Sixth Medical Center of PLA General Hospital between April 2014 and March 2018. All the patients were treated with haplo-HSC combined with tpCB transplantation. The median age of the patients was 3.5 years. The donor was the father in 25 cases and an aunt in 1 case. Transplantation was 5/6 HLA-matched in 9 cases, 4/6 in 12 cases, and 3/6 in 5 cases. The patients received busulfan, cyclophosphamide, fludarabine, or anti-thymocyte globulin for myeloablative preconditioning. Cyclosporine A and mycophenolate mofetil were used for prevention of acute graft-versus-host disease (aGVHD). Then the patients were treated with haploid bone marrow hematopoietic stem cells combined with tpCB transplantation on day 1 and haploid peripheral hematopoietic stem cells on day 2. The counts of median donor total nucleated cells, CD34 cells, and CD3 cells were 14.6×10/kg, 5.86×10/kg, and 2.13×10/kg respectively. RESULTS: The median time to neutrophil and platelet engraftment was 12 and 23 days after transplantation respectively. Full donor hematopoietic chimerism was observed on day 30. Twenty-five cases were from haplo-HSC and 1 was from cord blood. No primary implant failure and implant dysfunction occurred, and secondary implant failure occurred in one case. The NADPH oxidase activity returned to normal one month after transplantation. The incidence of grade I-II aGVHD and grade III-IV aGVHD was 35% and 15% respectively. Chronic GVHD (cGVHD) of the skin occurred in one case, and no progression was observed after steroid administration. During the follow-up period of 6-51 months, 25 patients survived, of whom 24 were disease-free (23 patients without cGVHD and 1 with cGVHD of the skin) and NADPH oxidase activity returned to normal; one patient developed secondary implant failure but survived; one patient died of viral interstitial pneumonia 16 months after transplantation. The 5-year event-free survival rate and overall survival rate were 81%±12% and 89%±10% respectively. CONCLUSIONS Haplo-HSC combined with tpCB transplantation is one of the effective methods for the treatment of X-CGD in children.
Child, Preschool ; Cord Blood Stem Cell Transplantation ; Graft vs Host Disease ; Granulomatous Disease, Chronic ; Haploidy ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Male ; Retrospective Studies ; Transplantation Conditioning

BACKGROUND: Leprosy is a contagious chronic granulomatous disease and is a disease that is associated with defects in cellular immunity. A high prevalence of hepatitis C virus infection in leprosy patients has been reported in several African countries, Yemen, Brazil and Japan. In Korea, it's seropositivity was reported as 8.33%(2001), 39.3%(2002), 35.1%(2009) and 16.0%(2009) on Korean Leprosy Bulletin. OBJECTIVE: In the meantime, the studies were limited to the subjects in a specific region, and the number of subjects was not enough, so it was not enough to evaluate the hepatitis C virus seropositivity of persons affected by leprosy in Korea. So this study was conducted to evaluate the it's seropositivity in settlement villages nationwide. METHOD: This study was conducted that the mobile team visited the resettlement villages nationwide from 2009 to 2017 and conducted on persons affected by leprosy and residents residing in resettlement village. Obtained serums were assayed by the ADVIA Centaur HVC(IgG antibodies to Hepatitis C Virus) reagent using a Siemens ADVIA Centaur CP instrument. The results of persons affected by leprosy and residents were compared, and the difference of seropositivity among the groups(male and female, multibacillary and paucibacillary, locations of resettlement villages) was evaluated. RESULT: The results of hepatitis C virus antibody positivity of 1669 persons affected by leprosy subjects and 185 residents of resettlement villages were 28.46% in persons affected by leprosy and 6.49% in residents(Pearson's Chi-Square test, P = 0.00). In persons affected by leprosy, that were 31.99%(male) and 26.84%(female)(Pearson's Chi-Square test, P = 0.06) and were 29.97%(multibacillary) and 25.36%(paucibacillary)(Pearson's Chi-Square test, P = 0.05). That of Seoul(48.28%), Busan(43.78%) and Chungbuk Province(35.94%) were highly positive and that of Gangwon Province(20.34%) was lowly positive(Fisher's Exact test P = 0.002). CONCLUSION: In this study, we found that hepatitis C virus antibody positivity rate was high in persons affected by leprosy in Korea. In order to explain the high positive rate, further studies will be needed. Also, through various approaches including assessment of HCV RNA to the subjects who were judged to be positive for antibody test in the future, a comprehensive evaluation of hepatitis C and its countermeasures are needed.
Antibodies ; Brazil ; Chungcheongbuk-do ; Female ; Gangwon-do ; Granulomatous Disease, Chronic ; Hepacivirus* ; Hepatitis C* ; Hepatitis* ; Humans ; Immunity, Cellular ; Japan ; Korea* ; Leprosy* ; Methods ; Prevalence ; RNA ; Yemen

During the past decades, there has been a great evolution in the field of fetal therapy for congenital defects. Prenatal screening or diagnostic methods including non-invasive and invasive methods and fetal ultrasound have led to earlier and more accurate diagnosis of congenital anomalies. Recent advances in several therapeutic techniques including ultrasound-guided needle therapy, laser therapy or fetal endoscopy, have allowed some fetuses at risk with anatomical defects, to be corrected in utero but still, its clinical indications remain limited. Over the last 30 years, many researchers found usefulness of pluripotent stem cells from amniotic fluid and placenta because they are sources of diverse progenitor cell populations called mesenchymal stem cells. In some human conditions like severe combined immunodeficiency syndrome and chronic granulomatous disease, fetal therapy using stem cell replacement showed some promising results in researches but more studies are required to apply in clinical settings. The aim of this article is to summarize a current status and future perspective of stem cell therapy for treatment of congenital fetal anomalies.
Amniotic Fluid ; Congenital Abnormalities ; Diagnosis ; Endoscopy ; Female ; Fetal Therapies* ; Fetus ; Granulomatous Disease, Chronic ; Humans ; Laser Therapy ; Mesenchymal Stromal Cells ; Needles ; Placenta ; Pluripotent Stem Cells ; Prenatal Diagnosis ; Severe Combined Immunodeficiency ; Stem Cells* ; Ultrasonography

Sarcoidosis is a chronic granulomatous disease, involving multisystem, confirmed by the presence of non-caseating granulomas. Sinonasal involvement in sarcoidosis is rare and difficult to diagnose since the symptoms of nasal obstruction and rhinitis are nonspecific. The diagnosis of sarcoidosis begins with clinical suspicion, followed by with imaging, and finally confirmed with tissue biopsy. In this study, we report a case of sarcoidosis of the nasal septum, which was early confirmed by a biopsy of the nasal septum and hilar lymph node.
Biopsy ; Diagnosis ; Granuloma ; Granulomatous Disease, Chronic ; Lymph Nodes ; Nasal Obstruction ; Nasal Septum* ; Rhinitis ; Sarcoidosis*

Chronic Granulomatous Disease (CGD) is caused by defects in the phagocyte NADPH oxidase and occurs in approximately 1:200,000 births worldwide. It presents with early onset of severe recurrent bacterial and fungal infections. This is a case of a 9-year old male with severe, recurrent bacterial infections since 3 weeks of age. Initial Nitroblue tetrazolium (NBT) reduction tests were normal but a DNA analysis revealed a previously unreported homozygous mutation in CYBB, p.S418Y. Dihydrorhodamine (DHR) test showed poor neutrophil oxidation consistent with X-linked CGD. Definitive microbiologic diagnosis is essential for directing therapy for recurrent bacterial and fungal infections. Treatment of infections should be aggressive. Lifelong bacterial and fungal prophylaxis is necessary for prolonged survival. We report a case of confirmed CGD with the previously unreported mutation.
Granulomatous Disease

Chronic granulomatous disease (CGD) is a rare inherited disorder caused by defective nicotinamide adenine dinucleotide phosphate oxidase enzyme and characterized by recurrent bacterial and fungal infections. Although liver abscess is a common manifestation of CGD, its management in CGD patients is not well-defined. In addition, the generalized guidelines for treating liver abscesses do not necessarily apply to CGD patients. Corticosteroids are commonly used to control granulomatous complications, such as inflammatory gastrointestinal and genitourinary lesions, in patients with CGD, Corticosteroids have also been used in combination with antimicrobials to treat refractory infections in patients with CGD. Because corticosteroids are capable of suppressing symptomatic inflammation, all potential infections must be adequately controlled prior to corticosteroid initiation. We report 3 typical CGD cases with liver abscesses refractory to conventional treatments that were successfully treated with the concomitant use of corticosteroid and antimicrobials. It remains unclear whether corticosteroid therapy is required for liver abscesses in CGD refractory to conventional treatments. However, based on our observations, use of corticosteroids in combination with optimal antimicrobials should be considered for refractory liver abscesses in CGD.
Adrenal Cortex Hormones ; Granulomatous Disease, Chronic* ; Humans ; Inflammation ; Liver Abscess* ; Liver* ; NADP ; Oxidoreductases

Chronic granulomatous disease (CGD) is a primary immunodeficiency disease caused by impaired phagocytic function. Hematopoietic stem cell transplantation (HSCT) is a definitive cure for CGD; however, the use of HSCT is limited because of associated problems, including transplantation-related mortality and engraftment failure. We report a case of a patient with CGD who underwent successful HSCT following a targeted busulfan and fludarabine reduced-toxicity myeloablative conditioning. Intravenous busulfan was administered once daily for 4 consecutive days (days –8 to –5), and the target area under the curve was 75,000 µg·hr/L. Fludarabine (40 mg/m2) was administered once daily for 6 consecutive days from days –8 to –3. Antithymocyte globulin (2.5 mg/kg/day) was administered from days –4 to –2. The patient underwent successful engraftment and did not have any severe toxicity related to the transplantation. Conditioning with a targeted busulfan and fludarabine regimen could provide a better outcome for HSCT in CGD, with close regulation of the busulfan dose.
Antilymphocyte Serum ; Bone Marrow Transplantation* ; Bone Marrow* ; Busulfan* ; Granulomatous Disease, Chronic* ; Hematopoietic Stem Cell Transplantation ; Humans ; Mortality ; Transplantation Conditioning