소아청소년 만성 복통증의 진단적 접근의 실제

황진복,정성훈 대한의사협회 2009 대한의사협회지 Vol.52 No.3

Chronic abdominal pain (CAP) in children and adolescents remains one of the pathogenetically ambiguous disorders and a great trouble to their caretakers as well as patients. Although the symptom does not usually lead to a crucial problem, the parents may be terribly worried, the child may be in distress, and the practitioner may be concerned about ordering tests to confirm a serious occult disease. Systemized diagnostic approaches are needed to overcome this unique difficulty. The presence of red flag symptoms or signs is a general indication to pursue diagnostic testing for organic etiologies of CAP on the basis of specific symptoms in an individual case. Functional abdominal pain can be normally diagnosed when there are no red flag symptoms or signs. According to the Rome III criteria for pediatric functional gastrointestinal disorders, functional disorders of CAP can be classified into functional dyspepsia, irritable bowel syndrome, abdominal migraine, and chronic functional abdominal pain syndrome. Cyclic vomiting syndrome and pathologic aerophagia are also major functional causes of CAP. Modern concepts of the pathogenesis of functional abdominal pain include brain-gut interaction, visceral hypersensitivity, autonomic dysfunction, and psychosocial factors. In addition, psychiatric disorders, presented with red flag symptoms or signs, may induce the CAP in children and adolescents. We introduce practical and systemized diagnostic approaches by illustrating clinical cases of CAP in children and adolescents.

Food protein-induced proctocolitis: Is this allergic disorder a reality or a phantom in neonates?

황진복,홍지나 대한소아청소년과학회 2013 Clinical and Experimental Pediatrics (CEP) Vol.56 No.12

The etiology of small and fresh rectal bleeding in neonates who are not sick is usually unknown; the only known cause is food protein-induced proctocolitis (FPIPC). It has been recently reported that FPIPC is a rare cause of rectal bleeding in newborns, and most cases have been proved to be due to idiopathic neonatal transient colitis. A recommended strategy for diagnosing suspected FPIPC in neonates is as follows. During the early stage, the etiology of small and fresh rectal bleeding in an otherwise healthy newborn need not be studied through extensive investigations. In patients showing continued bleeding even after 4 days,sigmoidoscopy and rectal mucosal biopsy may be performed. Even if mucosal histological findings indicate a diagnosis of FPIPC, further oral food elimination and challenge tests must be performed sequentially to confirm FPIPC. Food elimination and challenge tests should be included in the diagnostic criteria of FPIPC.

주기성 구토증(cyclic vomiting syndrome)의 장기 추적 관찰 -이형 편두통(migraine variant)으로의 이행 과정인가?-

황진복,오희종,최광해,Hwang, Jin-Bok,Oh, Hee-Jong,Choi, Kwang-Hae 대한소아소화기영양학회 2000 Pediatric gastroenterology, hepatology & nutrition Vol.3 No.1

저자들은 주기성 구토증으로 진단된 3명의 소아에서 6년 이상의 장기 추적관찰을 통하여 임상양상의 다양한 변화과정을 관찰하여 보고, 뇌파검사의 이상소견을 근거로 이형 편두통의 형태로 진행하여 가는 과정을 관찰하였다. 시간의 경과에 따라 구토 발병 주기, 기간의 변화와 함께 위배출능 저하, 두통의 발현, 뇌파의 이상 등 다양한 임상 양상의 변화를 보여주며, 2례에서는 증상의 소실이 관찰되었다. 특히, 뇌파 검사상 증상 발현시 발생하는 서파는 편두통의 발생 직전에 뇌혈류의 감소로 발생하는 양상과 매우 유사하며, 주기성 구토증과 편두통의 관련성을 시사하여 주는 소견으로, 진단 및 치료적 접근시 반드시 고려하여야 한다. 주기성 구통증은 이형 편두통으로의 이행 과정인가? Cyclic vomiting syndrome(CVS) is a disorder of unknown etiology that is characterized by its clinical pattern of intermittent episodes of severe vomiting, similar in time of onset and duration, with no symptoms during the intervening period. By definition, CVS is an idiopathic disorder that requires exclusionary laboratory testing. Not only can it be mimicked by many specific disorders, eg, surgical, neurologic, endocrine, metabolic, renal, but within idiopathic CVS there may be specific subgroups that have different mechanisms. It has been reported that CVS usually begins in toddlers and resolves during adolescence. Migraine is also self-limiting episodic condition of children and the clinical features of migraine and CVS show considerable similarity. It is proposed that CVS is a condition related to migraine. This paper reports clinical courses of long term follow-up and reversible EEG changes in three patients whose history included CVS. Clinical situations of attack interval, duration and associated symptoms had changed variablely in each patients through long term follow-up period. Cyclic vomiting subsided in two cases. Abnormal delta activity was seen during episodes and resolved at follow-up, when the patient asymptomatic. The brain wave changes support the interpretation of CVS as a migraine variant.

우유 단백질 유발성 장염 증후군의 병리 기전으로 세포 자멸사와 TNF-${\alpha}$, TRAIL receptor 1 (DR4)의 발현 증가

황진복,김상표,강유나,이성룡,서성일,권택규,Hwang, Jin-Bok,Kim, Sang-Pyo,Kang, Yu-Na,Lee, Seong-Ryong,Suh, Seong-Il,Kwon, Taeg-Kyu 대한소아청소년과학회 2010 Clinical and Experimental Pediatrics (CEP) Vol.53 No.4

목 적: 융모 위축을 보이는 FPIES 환자의 소장 점막에는 TNF-${\alpha}$의 발현이 증가한다. TNF-${\alpha}$는 상피 세포의 세포 자렴사를 유발하는 것으로 알려져 있다. 저자들은 FPIES 병리생리의 특성을 알아보고자 십이지장 점막 조직에서 TNF family와 TNF-수용체 family의 세포 자멸사를 연구하였다. 방 법: 표준화된 경구 유발 시험을 통하여 FPIES로 진단된 15례의 환자와 5례의 대조군을 대상으로 연구하였다. 세포 자멸사를 확인하기 위하여 terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) 염색을 시행하였다. 세포 자멸의 기전을 알아 보기 위해 TNF family의 TNF-${\alpha}$, Fas ligand (FasL)와 TNF-수용체 family의 TNF-related apoptosis-including ligand (TRAIL) receptor 1 (DR4), TRAIL receptor 2 (DR5), Fas를 면역조직화학으로 염색하였다. 결 과: $TUNEL^+$ 세포는 대조군에 비하여 FPIES 환자군의 십이지장 점막에서 의미 있게 높게 발현하였다($P$=0.043). TNF-${\alpha}$ ($P$=0.0001)와 DR4 ($P$=0.003)도 대조군에 비하여 FPIES군에서 의미 있게 높게 발현하였다. FasL, Fas, DR5의 발현은 두 군 모두에서 낮았으며, 두 군간에 의미 있는 차이를 보이지도 않았다. 결 론: FPIES의 병리생리는 세포 자멸사에 의하여 발생하며, TNF-${\alpha}$의 발현과 DR4 경로가 세포 자멸사에서 중요한 역할을 하는 것으로 추정된다. Purpose : Expression levels of tumor necrosis factor (TNF)-${\alpha}$ expression on the mucosa of the small intestine is increased in patients with villous atrophy in food protein-induced enterocolitis syndrome (FPIES). TNF-${\alpha}$ has been reported to induce apoptotic cell death in the epithelial cells. We studied the TNF family and TNF-receptor family apoptosis on the duodenal mucosa to investigate their roles in the pathogenesis of FPIES. Methods : Fifteen infants diagnosed as having FPIES using standard oral challenge test and 5 controls were included. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining was performed to identify the apoptotic cell death bodies. Immunohistochemical staining of TNF-${\alpha}$, Fas ligand (FasL) for TNF family and TNF-related apoptosis-including ligand (TRAIL) receptor 1 (DR4), TRAIL receptor 2 (DR5), and Fas for TNF-receptor family were performed to determine the apoptotic mechanisms. Results : $TUNEL^+$ was significantly more highly expressed in the duodenal mucosa of FPIES patients than in controls ($P$-0.043). TNF-${\alpha}$ ($P$=0.0001) and DR4 ($P$=0.003) were significantly more highly expressed in FPIES patients than in controls. Expression levels of FasL, Fas, and DR5 were low in both groups and were not significantly different between the 2 groups. Conclusion : These results suggest that FPIES pathogenesis is induced by apoptosis, and that TNF-${\alpha}$ expression and DR4 pathway may have an important role in apoptosis.

영유아 영양 장애의 조기 발견과 그 실례

황진복 한국모자보건학회 1999 한국모자보건학회 학술대회 연제집 Vol.1999 No.1

Is This Symptom Even a Food Allergy?: Clinical Types of Food Protein-induced Enterocolitis Syndrome

황진복 대한소아소화기영양학회 2014 Pediatric gastroenterology, hepatology & nutrition Vol.17 No.2

Food protein-induced enterocolitis syndrome (FPIES) is an under-recognized non-IgE-mediated gastrointestinal food allergy. The diagnosis of FPIES is based on clinical history, sequential symptoms and the timing, after excluding other possible causes. It is definitively diagnosed by an oral food challenge test. Unfortunately, the diagnosis of FPIES is frequently delayed because of non-specific symptoms and insufficient definitive diagnostic biomarkers. FPIES is not well recognized by clinicians; the affected infants are often mismanaged as having viral gastroenteritis, food poisoning, sepsis, or a surgical disease. Familiarity with the clinical features of FPIES and awareness of the indexes of suspicion for FPIES are important to diagnose FPIES. Understanding the recently defined clinical terms and types of FPIES is mandatory to suspect and correctly diagnose FPIES. The aim of this review is to provide a case-driven presentation as a guide of how to recognize the clinical features of FPIES to improve diagnosis and management of patients with FPIES.

영아기 알러지성 장병변 : 점막 면역학을 통한 새로운 접근

황진복 주식회사 녹십자 1994 녹십자의보 Vol.22 No.6

우유 과민성 장병증(cow's milk-sensitive enteropathy)에서 소장 생검조직의 형태학적 계측을 이용한 정량적 분석

황진복,김용진,Hwang, Jin-Bok,Kim, Yong-Jin 대한소아소화기영양학회 1998 Pediatric gastroenterology, hepatology & nutrition Vol.1 No.1

목 적: 우유 과민성 장병증(cow's milk-sensitive enteropathy, CMSE)은 우유를 식이 하였을 때 유해 반응과 함께 발생하는 상부 소장 점막의 손상이 병리적 특징으로 관찰되며, 이러한 점막의 손상은 우유를 제거하면 회복될 수 있고, 다시 유발시험을 하면 재발될 수 있다. CMSE 환자에서 소장 점막 손상의 정도를 형태학적 계측을 이용하여 정량적으로 분석하여 보고, 이를 이용한 CMSE의 진단적 가치 및 병리적 특성에 관하여 알아보고자 본 연구를 시행하였다. 대상 및 방법: 1994년 3월부터 1996년 6월까지 만성 설사와 성장 장애를 주소로 대구효성가톨릭 대학병원 소아과에 입원한 환자에서 우유에 대한 유발, 제거시험에 따른 임상적 반응 및 상부위장 관내시경을 시술하여 얻게 된 십이지장부의 생검조직 소견을 통하여 CMSE로 진단된 생후 $30.4{\pm}11.7$(14~56)일된 13명의 환아를 대상으로 하였다. 소장 생검조직의 형태학적 계측을 이용하여 융모 높이(villous height, VH), 음와 영역 깊이(crypt zone depth, CZD), 점막전체 두께(total mucosal thickness, TMT), 음와 영역에 대한 융모의 상대적 높이(VH/CD), 융모 1 mm당 상피세포간 림프구의 수(interepithelial lymphocytes, IEL), 0.5 mm의 점막근육판(muscularis mucosa)에 해당하는 상피 표면의 길이(length of surface epithelium, LSE), 상피층의 호산구 침윤(EOS-EP), 고유층(lamina propria)의 호산구 침윤(EOS-LP)을 측정하고, 대조군 및 회복기 생검 조직과 비교하였다. 결 과: 1) VH는 CMSE 환자군에서 $135{\pm}59\;{\mu}m$으로 대조군 $408{\pm}48\;{\mu}m$에 비하여 유의하게 낮았으며(p<0.001), 전례에서 융모 위축의 소견이 관찰되었다. 2) CZD는 CMSE 환자군에서 $311{\pm}65\;{\mu}m$으로 대조군 $188{\pm}24\;{\mu}m$에 비하여 유의하게 깊었다(p<0.05). 3) TMT는 CMSE 환자군에서 $449{\pm}56\;{\mu}m$으로 대조군 $596{\pm}71\;{\mu}m$에 비하여 유의하게 낮았다(p<0.001). 4) VH/CD는 CMSE 환자군에서 $0.46{\pm}0.28$로 대조군 $2.17{\pm}0.12$에 비하여 유의하게 낮았다(p<0.001). 5) LSE는 CMSE 환자군에서 $889{\pm}231\;{\mu}m$으로 대조군 $2547{\pm}378\;{\mu}m$에 비하여 유의하게 낮았다(p<0.001). 6) IEL은 CMSE 환자군에서 $34.1{\pm}10.5$개로 대조군 $13.6{\pm}3.6$개에 비하여 유의하게 높았다(p=0.001). 7) EOS-EP는 CMSE 환자군에서 $0.47{\pm}0.83$개로 의미 있는 침윤은 관찰되지 않았으며, 대조군 $0.80{\pm}0.84$개와 유의한 차이는 보이지 않았다. EOS-LP는 환자군에서 $2.67{\pm}3.72$개로 의미 있는 침윤은 관찰되지 않았으며, 대조군 $4.0{\pm}2.5$개와 유의한 차이를 보이지 않았다. 8) 회복기의 형태학적 변화는 VH $320{\pm}34\;{\mu}m$, CZD는 $194{\pm}19\;{\mu}m$, TMT $514{\pm}21\;{\mu}m$, VH/CD $1.41{\pm}0.25$, LSE $1840{\pm}210\;{\mu}m$, IEL $10.8{\pm}2.3$개로 관찰되었다. 결 론: 소장 조직의 생검은 상부위장관내시경을 이용하여도 그 임상적 유용성이 높으며, CMSE 환자에서 소장 점막의 손상은 형태학적 계측을 통하여 정량적으로 평가할 수 있으며 진단적 민감도가 높다. CMSE에서 점막의 손상은 빠른 융모 상피의 손상에 대한 음와 세포의 충분한 보상의 실패로 사료되며, 단백질 가수분해물의 수유후 빠른 회복이 관찰되었다. Purpose: To make objective standards of small intestinal mucosal changes in cow's milk-sensitive enteropathy (CMSE) we analyzed histological changes of endoscopic duodenal mucosa biopsy specimens from normal children and patients of CMSE. Methods: We review the medical records of patients who had been admitted and diagnosed as CMSE by means of gastrofiberscopic duodenal mucosal biopsy following cow's milk challenge and withdrawal. Thirteen babies with CMSE, ranging from 14 days to 56 days of age, were studied. Five non-CMSE patients were used as control, ranging from 22 days to 72 days of age. The morphometric parameters under study were villous height, crypt zone depth, ratio of villous height to crypt zone depth, total mucosal thickness and length of surface epithelium by using H & E stained specimens under the drawing apparatus attached microscope. In addition, the numbers of lymphocytes in the epithelium and eosinophil cells in the lamina propria and epithelium were measured. Results: In the duodenal mucosal biopsy specimens in CMSE we found partial and subtotal villous atrophy with an increased number of interepithelial lymphocytes. The mean villous height($135{\pm}59\;{\mu}m$), ratio of villous height to crypt zone depth ($0.46{\pm}0.28$), total mucosal thickness ($499{\pm}56\;{\mu}m$), length of surface epithelium of small intestinal mucosa ($889{\pm}231\;{\mu}m$) in CMSE was significantly decreased compared with the control (p<0.05). The mean crypt zone depth ($311{\pm}65\;{\mu}m$) was significantly greater than the control ($188{\pm}24\;{\mu}m$)(p<0.05). Infiltration of interepithelial lymphocytes ($34.1{\pm}10.5$) were significantly greater than the control ($13.6{\pm}3.6$)(p<0.05). The number of eosinophil cells in both lamina propria and epithelium was no significant differences between groups (p>0.05). The small intestinal mucosa in treated CMSE showed much improved enteropathy of villous height, crypt zone depth, interepithelial lymphocytes compared with the control as well as untreated CMSE. Conclusion: Quantitation of mucosal dimensions confirmed the presence of CMSE. It seems to be a limitation in the capacity of crypt cells to compensate for the loss of villous epithelium in CMSE. Specimens obtained by gastrofiberscopic duodenal mucosal biopsy were suitable for morphometric diagnosis of CMSE. Improvement of CMSE also can be confirmed histologically after the therapy of protein hydrolysate.

The Significance of Gastric Juice Analysis for a Positive Challenge by a Standard Oral Challenge Test in Typical Cow’s Milk Protein-Induced Enterocolitis

황진복,Jeong Yoon Song,강유나,김상표,서성일,감신,Won Joung Choi 대한의학회 2008 Journal of Korean medical science Vol.23 No.2

This study was performed to investigate the significance of gastric juice analysis (GJA) as a diagnostic criterion of a positive challenge in a standard oral cow’s milk challenge (OCC) to confirm typical cow’s milk protein-induced enterocolitis (CMPIE). Data from 16 CMPIE patients (aged 14 to 44 days) were analyzed. A standard OCC was openly executed using 0.15 g/kg of protein. Three symptoms (vomiting, lethargy, and bloody or pus-like stool), and four laboratory findings (GJA [3 hr], changes in peripheral blood absolute neutrophil count [ANC] [6 hr], C-reactive protein [6 hr], and stool smear test for occult blood or leukocytes) were observed after OCC. Before OCC, baseline studies were conducted; a stool smear test, blood sampling, and GJA. Positive OCC results were; vomiting (87.5%) (observed 1-3 hr after OCC), lethargy (62.5%) (1-3 hr), bloody or pus-like stool (43.8%) (6-10 hr), abnormal GJA (93.8%), an ANC rise >3,500 cells/ L (93.8%), and an abnormal stool smear test (75.0%). A single GJA test after a standard OCC is a sensitive diagnostic criterion of a positive challenge, and may provide an early confirmatory diagnosis of CMPIE. An investigation of positive OCC outcomes helps to find out a diagnostic algorithm of criteria of a positive challenge in CMPIE.

영유아 식품알레르기의 임상적 조망

황진복,Hwang, Jin-Bok 대한소아소화기영양학회 2011 Pediatric gastroenterology, hepatology & nutrition Vol.14 No.2

Food allergies affect 7~8% of infants and young children, and their prevalence appears to have increased in recent years. Food allergy refers to an abnormal immunological reaction to a specific food. These reactions can be recurrent each time the food is ingested. Food allergy manifests itself with a wide spectrum of clinical characteristics including IgE-mediated diseases as immediate reactions, non-IgE-mediated disorders as delayed reactions, and mixed hypersensitivities. As a consequence, the clinical picture of a food allergy is pleomorphic. A well-designed oral food challenge is the most reliable diagnostic test for infants and young children whose clinical history and physical examination point towards a specific food allergy. Food specific IgE antibody tests (RAST, MAST, skin prick test, Uni-CAP, etc) are an alternative tool to determine oral food challenge for IgE-mediated disorders, but not for non-IgE-mediated allergies. Moreover, parents often impose their children on unnecessary diets without adequate medical supervision. These inappropriate dietary restrictions may cause nutritional deficiencies. This review aims to introduce clinical perspectives of food allergy in infants and young children and to orient clinicians towards different strains of diagnostic approaches, dietary management, and follow-up assessment of tolerance development.