Incidence and causative agent distribution of viral-induced paediatric asthma exacerbations under strict infection control measures: a single-centre retrospective study in Japan.

BACKGROUND: The prevalence of respiratory viruses in children changed under strict infection control measures during the coronavirus disease 2019 (COVID-19) outbreak. In this study, we investigated the frequency of viral detection in the nasopharynx of paediatric patients with asthma exacerbations requiring hospitalization during the COVID-19 pandemic, as well as the distribution of causative viruses. METHODS: We included paediatric patients admitted for asthma exacerbations between November 2020 and December 2022 at a single centre in Kobe, Japan. Demographic, clinical, and laboratory data were collected from their medical records and using additional questionnaires. All patients enrolled in this study met the diagnostic criteria for asthma exacerbations outlined in the Japanese Pediatric Guideline for the Treatment and Management of Bronchial Asthma 2020. Statistical differences were calculated using univariate analyses (chi-square or Mann‒Whitney U test). RESULTS: We enrolled 203 children hospitalized for asthma attacks and collected nasopharyngeal samples from 189 patients. The median patient age was 3.0 years. Asthma severity was classified as mild (4.0%), moderate (82.3%), or severe (13.8%). The proportion of viral respiratory infections was 95.2% (180/189). The rate of patients with multiple viral infections was 20.6% (39/189). The most frequently detected pathogens were rhinovirus and enterovirus (RV/EV) at 69.3% (131/189), allowing for duplicate detection, followed by respiratory syncytial virus (RSV) at 28.6% (54/189). We also detected RV/EV almost every month compared to RSV and other viruses. In addition, RV/EV-positive patients were significantly older (p = 0.033), exhibited higher WBC counts (p < 0.001) and higher Eos counts (p < 0.001), had elevated total IgE levels (p < 0.001) and house dust mite-specific IgE levels (p = 0.019), had a shorter duration of hospitalization (p < 0.001), and had a shorter duration of oxygen therapy (p < 0.001). In patients positive for RV/EV, the use of ICSs significantly reduced the severity of the condition (p < 0.001). CONCLUSION: Even under strict infection control measures, respiratory viruses were detected in the nasopharynx of almost all paediatric patients who had asthma exacerbations requiring hospitalization.

Is oral food challenge test useful for avoiding complete elimination of cow's milk in Japanese patients with or suspected of having IgE-dependent cow's milk allergy?

BACKGROUND: Cow's milk, along with hen's egg, are common causes of food allergies in children worldwide. Accidental ingestion of milk is common and often induces severe allergic reactions. Oral food challenge test (OFC) is usually performed in patients with or suspected of having a food allergy. However, the evidence of whether cow's milk OFC is useful in IgE-dependent cow's milk allergy patients to avoid total elimination is not known. METHODS: After setting the clinical question and outcomes, we performed a systematic review for relevant articles published from January 1, 2000 to August 31, 2019 using PubMed® and Ichushi-Web databases. Each article was then evaluated for the level of evidence. All positive results of the OFC were defined as adverse events. RESULTS: Forty articles were selected in this study. Our review revealed that cow's milk OFC was able to avoid the complete elimination of cow's milk in 66% of the patients with cow's milk allergy. We also found that adverse events occurred frequently (50.5%). CONCLUSIONS: This analysis supports the recommendation of conducting cow's milk OFC to avoid complete elimination of cow's milk, however the test should be conducted with careful consideration of the patient's safety. As the methods of OFC and subjects varied among the articles selected in this study, further studies are needed to obtain higher quality evidence.

Is oral food challenge useful to avoid complete elimination in Japanese patients diagnosed with or suspected of having IgE-dependent hen's egg allergy? A systematic review.

BACKGROUND: IgE-mediated egg allergy is a common food allergy worldwide. Patients with egg allergy are known to easily achieve tolerance compared to other allergens such as nuts. Oral food challenge (OFC) is often performed on patients diagnosed with or suspected of having IgE-mediated food allergy, but whether hen's egg OFC is useful in IgE-dependent egg allergy patients to avoid complete elimination remains unknown. METHODS: We identified articles in which OFCs were performed in Japanese patients diagnosed with or suspected of having IgE-mediated egg allergy. We evaluated whether the OFCs were useful to avoid the complete elimination of eggs by assessing the following: (1) the number of patients who could avoid complete elimination; (2) the number of patients who experienced serious adverse events (SAEs); or (3) adverse events (AEs); (4) improvement in quality of life (QOL); and (5) immunological changes. RESULTS: Fifty-nine articles were selected in the study; all the references were case series or case studies in which OFC was compared to pre-challenge conditions. The overall negative ratio against egg OFC was 62.7%, but an additional 71.9% of OFC-positive patients could take eggs when expanded to partial elimination. Of the 4182 cases, 1146 showed AEs in the OFC, and two cases reached an SAE. Two reports showed an improvement in QOL and immunological changes, although the evidence was weak. CONCLUSIONS: OFCs against eggs may be useful to avoid complete elimination, but medical professionals should proceed with the test safely and carefully.

[NEED FOR SUBCUTANEOUS IMMUNOTHERAPY IN PEDIATRIC PATIENTS WITH ALLERGIC RHINITIS AFTER THE EXPANDED INDICATION FOR SUBLINGUAL IMMUNOTHERAPY].

BACKGROUND: Although the indication for sublingual immunotherapy (SLIT) was expanded in pediatric patients with allergic rhinitis in recent years, some patients choose subcutaneous immunotherapy (SCIT). OBJECTIVE: The objective of this study was to investigate the reason why they chose SCIT in spite of injection pain and high risk of systemic reaction. METHODS: The subjects were 58 patients who diagnosed with allergic rhinitis and introduced SCIT at our hospital between June 2018 and January 2021. The reasons why they chose SCIT were collected from medical records. RESULT: The median age at the start of treatment was 9 years 0 months. The most common reason why they chose SCIT was "difficult to maintain adherence of SLIT" in 28 cases (48%). Other reasons were as follows: "side effects of SLIT", "expectation for the effect of SCIT", "young age (under 5 years old)" and "motivation for allergic disease treatment". CONCLUSION: Two-thirds of the reasons why they chose SCIT were because it was difficult to continue SLIT for some reasons.

Clinical characteristics and treatment of 50 cases of Blau syndrome in Japan confirmed by genetic analysis of the NOD2 mutation.

OBJECTIVES: To collect clinical information and NOD2 mutation data on patients with Blau syndrome and to evaluate their prognosis. METHODS: Fifty patients with NOD2 mutations were analysed. The activity of each NOD2 mutant was evaluated in HEK293 cells by reporter assay. Clinical information was collected from medical records through the attending physicians. RESULTS: The study population comprised 26 males and 24 females aged 0-61 years. Thirty-two cases were sporadic, and 18 were familial from 9 unrelated families. Fifteen different mutations in NOD2 were identified, including 2 novel mutations (p.W490S and D512V); all showed spontaneous nuclear factor kappa B activation, and the most common mutation was p.R334W. Twenty-six patients had fever at relatively early timepoints in the disease course. Forty-three of 47 patients had a skin rash. The onset of disease in 9 patients was recognised after BCG vaccination. Forty-five of 49 patients had joint lesions. Thirty-eight of 50 patients had ocular symptoms, 7 of which resulted in blindness. After the diagnosis of Blau syndrome, 26 patients were treated with biologics; all were antitumour necrosis factor agents. Only 3 patients were treated with biologics alone; the others received a biologic in combination with methotrexate and/or prednisolone. None of the patients who became blind received biologic treatment. CONCLUSIONS: In patients with Blau syndrome, severe joint contractures and blindness may occur if diagnosis and appropriate treatment are delayed. Early treatment with a biologic agent may improve the prognosis.

Consensus statements on pediatric atopic dermatitis from dermatology and pediatrics practitioners in Japan: Goals of treatment and topical therapy.

BACKGROUND: Pediatric atopic dermatitis (PAD) is a pluricausal disease and is frequently seen in dermatological and pediatric practice. Therefore, it is important to find common views in clinical practice and to promote consensus among practitioners. Aiming to obtain common views among dermatologists and pediatricians and to disseminate them widely in clinical practice, we held the PAD Consensus Forums described herein. METHODS: Questionnaire surveys of treatment goals and drug therapy were conducted to prepare topics for discussion at the PAD Consensus Forums. Reaching consensus was defined as agreement among at least 70% of the participants. RESULTS: As a result of discussion among 24 dermatologists and 25 pediatricians, consensus was obtained on 7 topics. These topics configure 3 consensus of treatment goals (Attainment targets were divided into the short/medium term and the long term. Attainment targets were associated with the primary evaluation domains of the Harmonising Outcome Measures for Eczema (HOME) roadmap, etc.) and 4 consensus of drug therapy (The number of applications of topical anti-inflammatory drugs in the acute phase and selection and ideal intervals between applications of topical anti-inflammatory drugs in proactive therapy, etc.). CONCLUSIONS: The consensus is expected to help practitioners set appropriate treatment goals in clinical practice and facilitate the choice of drugs for treatment.

Disaster preparation: Survey of patients with food allergies in Kobe, Japan.

BACKGROUND: Securing food for patients with food allergies may be more difficult during disasters, but reports on the status of household allergen-free food reserves in preparation for disasters are limited. This study investigated the household stock status of allergen-free foods in preparation for disasters in Kobe City after the Great Hanshin-Awaji Earthquake. METHODS: The survey targets were 172 parents of patients with a food allergy who underwent in-hospital oral food challenge test for allergies at four hospitals from October 2016 to March 2017. Of these, 158 patients with allergies to eggs, milk and wheat were included in the analysis. The first survey was performed to investigate patient characteristics and stockpiling status of allergen-free foods in parallel with oral food challenge tests. The second survey was performed on the follow-up visit to investigate any changes in behavior. RESULTS: Median patient age was 3 years, with boys comprising 68.4% of the patients. Eggs were the most eliminated food, and the median number of foods avoided was 2. A total of 82.3% of parents had experienced disasters. The proportion of households that stockpiled allergy-free meals was 42.4%, and the median amount was 3 days. The stockpiling situation did not differ according to the parents' disaster experience. In the second survey, 45.3% had modified their stockpiling practice. CONCLUSIONS: Even in this area where the Great Hanshin-Awaji Earthquake occurred, household stockpiles of allergen-free foods are inadequate; therefore, all medical staff should educate families about the necessity of stocking allergen-free food for disasters.

[DIFFERENCE BETWEEN STANDARDIZED MITE ANTIGEN AND HOUSE DUST EXTRACT IN RUSH SUBCUTANEOUS IMMUNOTHERAPY FOR CHILDREN].

RATIONALE: Standardized allergen extracts are recommended for allergen immunotherapy. Since 2015, for patients with house dust mite allergies, we used a standardized house dust mite extract for subcutaneous immunotherapy, rather than non-standardized house dust extract. This study hypothesizes that standardized house dust mite extract (HDM group) was superior to non-standardized house dust extract (HD group) for subcutaneous immunotherapy. METHODS: In this noninterventional, retrospective study, we enrolled patients with allergic rhinitis and sensitization to house dust mites. The HDM group (27 patients) received subcutaneous standardized extract immunotherapy since 2015, and the HD group (37 patients) received non-standardized extracts before 2015. We assessed the safety and efficacy between the two groups; the safety was assessed by the systemic reaction (SR) rate. The efficacy was assessed by reductions in the allergic rhinitis symptom-medication score, and the asthma treatment score, over a year. RESULTS: The SR rate of the HDM group (44%) was significantly higher than that (14%) of the HD group. The HDM group displayed a 57% reduction in the allergic rhinitis symptom-medication score, which was markedly higher than the 40% reduction observed in the HD group. In the standardized group, there was a 66% reduction occurred in the asthma medication score, markedly higher than the 36% reduction observed among patients in the HD group. CONCLUSIONS: Standardized house dust mite extract was more effective than non-standardized house dust extract for subcutaneous immunotherapy; however, the establishment of safer methods is warranted.

A long-term follow-up of Japanese mother and her daughter with Blau syndrome: Effective treatment of anti-TNF inhibitors and useful diagnostic tool of joint ultrasound examination.

Blau syndrome (BS) is an autosomal dominant autoinflammatory disease associated with NOD2 gene mutations. It is characterized by arthritis, skin rash, and uveitis. Here, we report contrasting outcomes of a daughter and her mother with BS. Their long-term follow-up revealed the efficacy of anti-tumor necrosis factor inhibitor (TNF) with respect to BS. Joint findings of BS feature tenosynovitis over articular synovitis on ultrasonography. BS might be one of the differential diagnoses of juvenile idiopathic arthritis and rheumatoid arthritis.

[SAFETY AND EFFICACY OF ONE-YEAR RUSH SUBCUTANEOUS IMMUNOTHERAPY IN JAPANESE CHILDREN, USING HOUSE DUST EXTRACT].

BACKGROUND: In recent years there have been few reports on the effects of immunotherapy on bronchial asthma (BA) and allergic rhinitis (AR) in Japanese children. OBJECTIVE: To investigate the safety and efficacy of house dust extract immunotherapy for one year. METHODS: Thirty-five children with AR and BA were subjected to rush immunotherapy with house dust extract. Systemic reactions were counted to evaluate safety. BA medication score and AR symptom-medication score were recorded. RESULTS: Three patients (8.3% of all patients) experienced 6 systemic reactions (0.15% of doses). BA medication score decreased from 567 to 325 (a reduction rate of 43%). AR symptom-medication score improved from 5.1 to 2.9 (a reduction rate of 43%). CONCLUSIONS: Rush immunotherapy with house dust extract is safe and effective for Japanese children.

Autosomal dominant anhidrotic ectodermal dysplasia with immunodeficiency caused by a novel NFKBIA mutation, p.Ser36Tyr, presents with mild ectodermal dysplasia and non-infectious systemic inflammation.

PURPOSE: Anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) is characterized by hypohidrosis, dental abnormalities, sparse hair, and immunodeficiency. Autosomal dominant (AD)-EDA-ID, caused by a heterozygous mutation within NFKBIA, is very rare and its clinical features remain largely unknown. This study describes a patient with AD-EDA-ID harboring a novel NFKBIA mutation who presented with mild EDA and non-infectious systemic inflammation. METHODS: The clinical presentation of an AD-EDA-ID patient was described and immunological, genetic, and biochemical analyses were performed, with a focus on nuclear factor kappa B (NF-κB) activation. RESULTS: The patient presented with symptoms of mild EDA-ID, namely sparse hair and hypohidrosis, although a skin biopsy confirmed the presence of sweat glands. There were no dental abnormalities. The patient also suffered from non-infectious inflammation, which responded to systemic corticosteroid therapy; however, the patient remained ill. Immunological analyses revealed reduced Toll-like receptor/IL-1 (TLR/IL-1) and tumor necrosis factor (TNF) receptor family responses to various stimuli. Genetic analysis identified a de novo heterozygous missense mutation, p.Ser36Tyr, in NFKBIA, resulting in defective NFKBIA degradation and impaired NF-κB activation. The patient was diagnosed with AD-EDA-ID and underwent hematopoietic stem cell transplantation. Engraftment was successful, with few signs of acute graft versus host disease. However, the patient suffered hemolytic anemia and thrombocytopenia, and died from a brain hemorrhage due to intractable thrombocytopenia. CONCLUSION: AD-EDA-ID patients can present with mild ectodermal dysplasia and non-infectious inflammation, rather than with recurrent infections. Also, hematopoietic stem cell transplantation for AD-EDA-ID is still a clinical challenge.

The CD40-CD40L axis and IFN-γ play critical roles in Langhans giant cell formation.

The presence of Langhans giant cells (LGCs) is one of the signatures of systemic granulomatous disorders such as tuberculosis and sarcoidosis. However, the pathophysiological mechanism leading to LGC formation, especially the contribution of the T cells abundantly found in granulomas, has not been fully elucidated. To examine the role of T cells in LGC formation, a new in vitro method for the induction of LGCs was developed by co-culturing human monocytes with autologous T cells in the presence of concanavalin A (ConA). This system required close contact between monocytes and T cells, and CD4+ T cells were more potent than CD8+ T cells in inducing LGC formation. Antibody inhibition revealed that a CD40-CD40 ligand (CD40L) interaction and IFN-γ were essential for LGC formation, and the combination of exogenous soluble CD40L (sCD40L) and IFN-γ efficiently replaced the role of T cells. Dendritic cell-specific transmembrane protein (DC-STAMP), a known fusion-related molecule in monocytes, was up-regulated during LGC formation. Moreover, knock-down of DC-STAMP by siRNA inhibited LGC formation, revealing that DC-STAMP was directly involved in LGC formation. Taken together, these results demonstrate that T cells played a pivotal role in a new in vitro LGC formation system, in which DC-STAMP was involved, and occurred via a molecular mechanism that involved CD40-CD40L interaction and IFN-γ secretion.

Safety of Low-Dose Oral Food Challenges for Hen's Eggs, Cow's Milk, and Wheat: Report from a General Hospital without Allergy Specialists in Japan.

An oral food challenge (OFC) is useful for managing food allergies. However, because OFCs have the risk of severe allergic reactions, including anaphylaxis, conducting OFCs under this situation without allergy specialists is difficult. To investigate the safety of a low-dose OFC for eggs, milk, and wheat in a general hospital without allergy specialists. We retrospectively analyzed the medical records of children who were hospitalized in a general hospital without allergy specialists for a low-dose OFC of egg, milk, or wheat between April 2018 and March 2021. The records of 108 patients were evaluated. The median age was 15.8 months (range: 7.5-69.3 months). Challenged foods were eggs (n = 81), milk (n = 23), and wheat (n = 4). Fifty-three (49.0%) patients showed positive allergic reactions. Thirty-five (66.0%) patients showed grade 1 (mild), 18 (34.0%) showed grade 2 (moderate), and none showed grade 3 (severe) reactions. The interventions comprised antihistamines (n = 18), prednisolone (n = 3), inhaled Β2-agonist (n = 2). No patients required adrenaline and no deaths occurred. Low-dose OFCs may be safe in a general hospital without allergy specialists. Conducting a low-dose OFC may be essential in food allergy practice.

Parents' Fears about Hospital Visits and Trait Anxiety in the COVID-19 Pandemic.

Anxiety in parents of children with allergic diseases during the COVID-19 pandemic may impact hospital visits. This study explored the effect of the pandemic on parents' fears about hospital visits and their relationship with their personality traits. A cross-sectional, questionnaire-based study was conducted between September 2020 and March 2021, with parents of children aged 0-15 years, who regularly visited 24 outpatient facilities for allergic disease. The survey included patient information, fears about hospital visits, desired information, and the State-Trait Anxiety Inventory. Responses were compared between parents with high and low trait anxiety. The response rate was 97.6% (2439/2500). The most common fear was "Fear of getting medical care as usual (85.2%)" and "Fear of COVID-19 infection during hospital visits (87.1%)". High trait anxiety showed a significant association with "Fear of worsening of children's allergies" (adjusted OR: 1.31, 95%CI: 1.04 to 1.65, p = 0.022), and "Fear of worsening of COVID-19 due to allergy" (adjusted OR: 1.52, 95%CI: 1.27 to 1.80, p < 0.01). Healthcare professionals should share updates on COVID-19 and healthcare system to reduce parents' fear. Subsequently, they should communicate the importance of continuing treatment to prevent worsening of COVID-19 and avoid emergency visits, considering parental trait anxiety.

Pediatric allergies in Japan: Coronavirus disease pandemic-related risk factors.

Background: The coronavirus disease 2019 (COVID-19) pandemic impacted various parts of society, including Japanese children with allergies. Objective: This study investigated risk factors for pediatric allergic diseases associated with the state of emergency owing to the COVID-19 pandemic in Japan, including during school closures. Methods: Parents of pediatric patients (0-15 years) with allergies were enrolled and queried regarding the impact of school closure on pediatric allergies compared to that before the COVID-19 pandemic. Results: A valid response was obtained from 2302 parents; 1740 of them had children with food allergies. Approximately 4% (62/1740) of the parents reported accidental food allergen ingestion was increased compared to that before the COVID-19 pandemic. Accidental ingestion during school closures was associated with increased contact with meals containing allergens meant for siblings or other members of the family at home. The exacerbation rate during the pandemic was highest for atopic dermatitis at 13% (127/976), followed by allergic rhinitis at 8% (58/697), and bronchial asthma at 4% (27/757). The main risk factors for worsening atopic dermatitis, allergic rhinitis, and bronchial asthma were contact dermatitis of the mask area (34/120 total comments); home allergens, such as mites, dogs, and cats (15/51 total comments); and seasonal changes (6/25 total comments), respectively. Conclusion: The main factors affecting allergic diseases were likely related to increased time at home, preventive measures against COVID-19, and refraining from doctor visits. Children with allergies were affected by changes in social conditions; however, some factors, such as preventing accidental ingestion and the management of allergens at home, were similar to those before the COVID-19 pandemic. Patients who had received instructions on allergen avoidance at home before the pandemic were able to manage their disease better even when their social conditions changed.

Acute liver failure in young children with systemic-onset juvenile idiopathic arthritis without macrophage activation syndrome: report of two cases.

Acute liver failure (ALF) with macrophage activation syndrome (MAS) is well known as a complication of systemic-onset juvenile idiopathic arthritis (S-JIA). However, liver failure without overt MAS is rare in S-JIA. We encountered two Japanese children with S-JIA in whom ALF developed during the remission of clinical manifestations. ALF without MAS was improved with plasma exchange and cyclosporine A combined with pulse methylprednisolone.

Progress of Home-Based Food Allergy Treatment during the Coronavirus Disease Pandemic in Japan: A Cross-Sectional Multicenter Survey.

The coronavirus disease 2019 (COVID-19) pandemic's impact on food allergy treatment such as home-based oral immunotherapy (OIT) is not known. This cross-sectional, questionnaire-based anonymized survey screened 2500 parents of children with allergic diseases and was conducted in the pediatric outpatient clinics of 24 hospitals. Basic clinical data of the children were collected along with the degree of allergy control, parental anxiety about emergency visits, and the risk of COVID-19 in the first state of emergency. A total of 2439 (97.6%) questionnaires were collected, and 1315 parents who were instructed to initiate home-based OIT for their children were enrolled (OIT group). Subjective OIT progress compared to before the COVID-19 pandemic was ascertained as "Full", "Middle", "Low", "Little", and "Stop" in 264 (20.1%), 408 (31.0%), 384 (29.2%), 203 (15.4%), and 56 (4.3%) participants, respectively. Anxiety about emergency visits and the risk of COVID-19 were negatively associated with the subjective OIT progress. In Japan, approximately half of the children continued smoothly the home-based OIT during the COVID-19 pandemic. Parents with high levels of anxiety about the disruption of the medical care system due to COVID-19 and the risk of COVID-19 did not experience a smooth continuation of home-based OIT.

Sustained Surface ICAM-1 Expression and Transient PDGF-B Production by Phorbol Myristate Acetate-Activated THP-1 Cells Harboring Blau Syndrome-Associated NOD2 Mutations.

OBJECTIVES: Blau syndrome is a distinct class of autoinflammatory syndrome presenting with early-onset systemic granulomatosis. Blau syndrome-causing NOD2 mutations located in the central nucleotide-oligomerization domain induce ligand-independent basal NF-κB activation in an in vitro reporter assay. However, the precise role of this signaling on granuloma formation has not yet been clarified. METHODS: Blau syndrome-causing NOD2 mutations were introduced into human monocytic THP-1 cells, and their morphological and molecular changes from parental cells were analyzed. Identified molecules with altered expression were examined in the patient's lesional skin by immunostaining. RESULTS: Although the production of proinflammatory cytokines was not altered without stimulation, mutant NOD2-expressing THP-1 cells attached persistently to the culture plate after stimulation with phorbol myristate acetate. Sustained surface ICAM-1 expression was observed in association with this phenomenon, but neither persistent ICAM-1 mRNA expression nor impaired ADAM17 mRNA expression was revealed. However, the transient induction of PDGF-B mRNA expression was specifically observed in stimulated THP-1 derivatives. In the granulomatous skin lesion of a Blau syndrome patient, ICAM-1 and PDGF-B were positively immunostained in NOD2-expressing giant cells. CONCLUSIONS: Sustained surface ICAM-1 expression and transient PDGF-B production by newly differentiating macrophages harboring mutant NOD2 might play a role in granuloma formation in Blau syndrome.

Tricho-hepato-enteric syndrome with novel SKIV2L gene mutations: A case report.

RATIONALE: Tricho-hepato-enteric syndrome (THES) is a rare disorder caused by mutations in the TTC37 or SKIV2L genes and characterized by chronic diarrhea, liver disease, hair abnormalities, and high mortality in early childhood due to severe infection or liver cirrhosis. PATIENT CONCERNS: The patient is the second child of three siblings born to non-consanguineous healthy Japanese parents. She had intrauterine growth retardation and was delivered at 33 weeks of gestation due to placental abruption. She presented with watery diarrhea, elevated levels of liver enzymes, multiple episodes of recurrent bacterial infection, and mild mental retardation. She had facial dysmorphism, including prominent forehead and hypertelorism, and had woolly hair without trichorrhexis nodosa. DIAGNOSIS: Clinical features led to consideration of THES. Novel compound heterozygous nonsense mutations, c.1420G>T (p.Q474*) and c.3262G>T (p.E1088*), in the SKIV2L gene were identified in the patient, and decreased levels of SKIV2L protein expression were revealed by flow cytometry and confirmed by western blot analysis using patient peripheral blood mononuclear cells (PBMCs). INTERVENTIONS: Total parenteral nutrition was required from day 30 to day 100. Trimethoprim-sulfamethoxazole prophylaxis was started at the age of 7 years after multiple episodes of bacterial pneumonia and otitis media. OUTCOMES: Chronic diarrhea persisted for more than 10 years, but the symptoms gradually improved with age. At the age of 13 years, she started a normal diet in combination with oral nutritional supplementation and her height and weight were just below the 3rd percentile for healthy individuals. She developed secondary sex characteristics, and menarche occurred at the age of 12 years. Facial dysmorphism, including prominent forehead and hypertelorism, and woolly hair without trichorrhexis nodosa became noticeable as she matured. LESSONS: Physicians must be aware of THES when they encounter a patient with infantile diarrhea, hair abnormalities, immune deficiency, mental retardation, and liver disease. Moreover, flow cytometric detection of SKIV2L protein in PBMCs may facilitate early diagnosis.