Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-γ immunity

Inborn errors of IL-12/23- and IFN-gamma-mediated immunity: molecular, cellular, and clinical features.

Revisiting Human IL-12Rβ1 Deficiency: A Survey of 141 Patients From 30 Countries

The importance of aspergillosis in humans and various animal species has increased over the last decades. Aspergillus species are found worldwide in humans and in almost all domestic animals and birds as well as in many wild species, causing a wide range of diseases from localized infections to fatal disseminated diseases, as well as allergic responses to inhaled conidia. Some prevalent forms of animal aspergillosis are invasive fatal infections in sea fan corals, stonebrood mummification in honey bees, pulmonary and air sac infection in birds, mycotic abortion and mammary gland infections in cattle, guttural pouch mycoses in horses, sinonasal infections in dogs and cats, and invasive pulmonary and cerebral infections in marine mammals and nonhuman primates. This article represents a comprehensive overview of the most common infections reported by Aspergillus species and the corresponding diseases in various types of animals.

Aspergillus and aspergilloses in wild and domestic animals: a global health concern with parallels to human disease.

Bacillus Calmette-Guérin (BCG) complications associated with primary immunodeficiency diseases

A huge ovarian mucinous cystadenoma in a 14-year-old premenarchal girl: review on ovarian mucinous tumor in premenarchal girls.

Complete interleukin-12 receptor β1 deficiency is the most frequent known genetic etiology of the syndrome of Mendelian susceptibility to mycobacterial diseases (MSMD, OMIM 209950). Eleven disorders caused by different types of mutations in five different gene defects related to the IL-12 and IL-23/interferon (IFN)-γ axis have been described to date [2]. Refer to Fig. 1 for the pathways of IL-12/IL-23-dependent interferon IFN-gamma immunity. Patients with MSMD are vulnerable to the BacillusCalmette-Guerin (BCG) vaccine species Mycobacterium bovis, environmental mycobacteria and M. tuberculosis. Infectious diseases other than those caused by Salmonella species, the latter of which infect almost one-half of all patients, are rare [1, 3, 6]. We report here various and unusual clinical manifestations of three unrelated patients with complete IL-12Rβ1 deficiency due to three different mutations in the IL-12RB1 gene, of which two are novel (711insC, 628–644dup). The first patient was an 1-year-old infant girl who had BCG lymphadenitis at 6 months of age and disseminated mycobacterial infection complicated with spontaneous pneumomediastinum and subcutaneous emphysema at 12 months of age. She was treated with isoniazide, rifampin, ethambutol, amikacin, clarithromycin and clofazimine. Pre-tracheal fasciotomy was undertaken for subcutaneous emphysema. A complete IL-12 receptor β1 deficiency associated with the 711insC mutation in IL-12RB1 was detected (Fig. 2). The patient is still in remission. The second patient was an 19-month-old infant boy who presented with five episodes of infections attributable to Salmonella and two episodes of Salmonella enteritidis meningitis. There was no mycobacterial disease, including no adverse reaction to BCG immunization that was practiced at the age of 2 months. He was treated with meropenem, rIFN-γ and external ventricular drainage and then ventriculo-peritoneal shunting for hydrocephalus. Immunologic and molecular genetic examinations revealed complete IL-12Rβ1 deficiency and a IL-12RB1 783+ 1G>A mutation (Fig. 2) [3]. The third patient, a 4.5-year-old boy, had fistulized BCG lymphadenitis in early childhood followed by disseminated mycobacterial infection and splenic abscess with Salmonella bacteremia at 44 months of age. He was treated with meropenem and with isoniazide, rifampin, ethambutol, clarithromycin and amikacin. The patient improved; however, he was lost to follow-up and has been reported to have died. DNA sequencing revealed a 628–644dup mutation in IL-12RB1 (Fig. 2). A complete IL-12 receptor β1 deficiency is suspected. All three patients had persistent oral moniliasis. Among a total of 56 cases of IL-12 receptor β1 deficiency reported in the literature, the rate of infection with BCG M. bovis is 73% (27/37), environmental mycobacteria 21% (22/56), non-typhoidal Salmonella species 46% (26/56) and tuberculosis 7% (4/56) [4–6]. Paracoccidioides brasiliensis-disseminated disease has also recently been reported in an IL-12Rβ1-deficient patient. None of the 37 patients with BCG disease subsequently G. Tanir (*) . N. Tuygun . C. Aydemir . E. C. Boduroglu Dr. Sami Ulus Children Health and Diseases Training and Research Center, Hosdere Caddesi 166/3, Yukari Ayranci, 06550 Ankara, Turkey e-mail: gonultanir58@yahoo.com Fax: +90-312-3170353

Complete deficiency of the IL-12 receptor β1 chain: three unrelated Turkish children with unusual clinical features

Ovarian steroid cell tumors are rarely encountered in prepubertal girls. The majority of these tumors produce hormones, testosterone being the leading one. These tumors may either coexist with or imitate congenital adrenal hyperplasia (CAH). We present a 13-year-old female patient who was diagnosed with non-classical CAH at six years of age while being investigated for premature pubarche. She was diagnosed with steroid cell ovarian tumor after a delay of six years. The diagnosis was based on radiologic imaging, which was performed to investigate causes of unsuccessful metabolic control while under high-dose steroid therapy. The right ovarian hypoechoic mass of 23x22 mm was excised laparoscopically, preserving the ovary. Immunohistochemical staining showed that tumor cells were strongly positive with inhibin and focally positive with vimentin. Based on these findings, the patient was diagnosed with ovarian steroid cell tumor not otherwise specified. In the postoperative second week, total testosterone level was <10 ng/ml, and 17 hydroxyprogesterone (17-OHP) level was 1.1 ng/ml. Peak 17-OHP level was 4.2 ng/ml on repeated ACTH stimulations, and the diagnosis of CAH was excluded. Steroid therapy was tapered down and then discontinued. It should be kept in mind that there may be a misdiagnosis in cases of CAH, which may present itself with unsuccessful metabolic control even while under the appropriate treatment dose. Early diagnosis and treatment would prevent the development of irreversible signs.

A girl with steroid cell ovarian tumor misdiagnosed as non-classical congenital adrenal hyperplasia.

Invasive aspergillosis is most commonly seen in patients with immune disorders and usually in the lung. Local invasive aspergillosis of the gastrointestinal system is quite rare. A 13-year-old female without immune deficiency presented with acute abdomen due to full-thickness necrosis of the gastric fundus. The necrotic gastric wall was excised and the stomach repaired. The pathology revealed a gastric ulcer with invading Aspergillus hyphae and spores. Aspergillosis is an opportunistic infection and its spores cannot survive in the normal gastric mucosa. The Aspergillus spores in this case probably grew on a background of gastric ulcer and caused wall necrosis and that the surgical treatment possibly provided a cure because it remained localized to the gastric wall.

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Invasive Aspergillus infection localized to the gastric wall: report of a case.

OBJECTIVE: In this study, we aimed to give a documentation of 37 cases of childhood fibroblastic/myofibroblastic tumors retrieved from the archives of 6 reference centers in Ankara along with a comprehensive review on the subject. MATERIAL AND METHOD: A retrospective archive search was carried out for the period between 2006-2010 in 6 reference centers in Ankara covering patients with ages ranging between 0-18 years. All the tumors categorized under fibroblastic and myofibroblastic group according to World Health Organization criteria were collected. RESULTS: The study comprised 407 soft tissue tumors in total. Fibroblastic/myofibroblastic tumors constituted 9,1 % (37 cases) of these tumors. According to histopathology; 16 cases were categorized as fibromatosis, 8 cases as inflammatory myofibroblastic tumor, 6 cases as infantile fibrous hamartoma, 3 cases as nodular fasciitis and 2 cases as infantile myofibroblastic tumor/myofibromatosis and 1 case as cranial fasciitis. The only malignant case was an infantile fibrosarcoma. CONCLUSION: Infantile fibrosarcoma was lower than reported series and a male predominance was noted. The low incidence of newly described entities as well suggests that these tumors may have been unrecognized.

/pdf/childhood-fibroblastic-and-myofibroblastic-tumors-a-3psukrijt5.pdf

Esin Boduroglu

Papers

A huge ovarian mucinous cystadenoma in a 14-year-old premenarchal girl: review on ovarian mucinous tumor in premenarchal girls.

Complete deficiency of the IL-12 receptor β1 chain: three unrelated Turkish children with unusual clinical features

A girl with steroid cell ovarian tumor misdiagnosed as non-classical congenital adrenal hyperplasia.

Invasive Aspergillus infection localized to the gastric wall: report of a case.

Childhood fibroblastic and myofibroblastic tumors: a multicenter documentation and review of the literature.