Diagnosis Of hyper-IgE Syndrome Research Articles

Challenges in diagnosing and managing hyper-IgE syndrome in a resource-limited setting: a case report

Introduction and Importance: Hyper-IgE Syndrome (HIES), also known as Job syndrome, is a rare immunodeficiency disorder characterized by elevated IgE levels and recurrent infections. Diagnosing and managing HIES in resource-limited settings is challenging due to the lack of advanced diagnostic tools. This report highlights the necessity of clinical evaluation and basic laboratory investigations for diagnosing HIES. Case Presentation: A 3-year-old male presented with fever, cough, and widespread pustular lesions. He had a history of recurrent respiratory infections and otitis media. Physical examination revealed characteristic facial features, skin findings, and laboratory investigations showed elevated IgE levels (>3000 IU/mL) and leukocytosis. A clinical diagnosis of HIES was made, and the patient responded well to antibiotics, antihistamines, and topical steroids. Clinical Discussion: Hyper-IgE Syndrome is caused by genetic mutations affecting immune function, primarily involving STAT3 and DOCK8 genes. Diagnosis in resource-limited settings relies on clinical features and basic investigations. Challenges include the unavailability of genetic testing. Management includes antibiotics and symptomatic relief adapted to available resources. Conclusion: Diagnosing and managing Hyper-IgE Syndrome in resource-limited settings requires adaptation of clinical approaches to available resources. This case underscores the importance of clinical vigilance and basic diagnostic tools in diagnosing rare immunodeficiencies.

Implications of Glycopeptide and Lipopeptide Antibiotics on Asthma Exacerbations in a Patient With Hyper-IgE Syndrome and Chronic Severe Asthma: A Case Report

Objective: To review and consider the immunomodulatory ramifications of glycopeptide and lipopeptide antibiotics in a patient with severe asthma, hyper-immunoglobulin E (IgE) syndrome, and osteonecrosis of the jaw. Case Summary: A 36-year-old male patient with a pertinent past medical history of hyper-IgE syndrome, severe asthma, and osteonecrosis of the jaw attributed to steroid use initially presented to the emergency department, where imaging of the jaw suggested an infectious process. Following months of vancomycin therapy as an outpatient, the patient was switched to daptomycin to facilitate once-daily infusions. Following this change, the patient experienced significantly less asthma exacerbations and fewer admissions to the hospital for asthma-related issues. Discussion: Though daptomycin is associated with eosinophilia, and this patient’s eosinophil counts did increase while on the drug, an inverse relationship developed concerning the number of hospital admissions for asthma exacerbations. A review of the literature indicates that select glycopeptides, such as vancomycin, have pro-inflammatory effects, while other related drugs, such as the lipopeptide daptomycin, may not result in clinical manifestations of an inflammatory process. Tumor necrosis factor-α, interleukin-1β, and interleukin-6 have been implicated in this process. This patient may have been particularly susceptible to the effects of the glycopeptides due to his diagnosis of hyper-IgE syndrome, which has been independently associated with reactive airway diseases. Conclusion: Cytokine migration and activation by select glycopeptide and lipopeptide antibiotics warrant consideration from clinicians when determining the most appropriate treatment regimens. Further research is required to elucidate whether the pro-inflammatory properties of vancomycin warrant a change in first-line therapy to daptomycin in select cases.

Hyper IgE syndrome associated with novel and recurrent STAT3 mutations

Rationale:Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency presenting as two forms including autosomal dominant HIES (AD-HIES) and autosomal recessive HIES (AR-HIES), which are mainly caused by mutations in STAT3 and DOCK8, respectively. To date, only about 500 cases have been reported worldwide including 37 cases in China. The spectrum and prevalence of mutations and molecular pathogenesis in HIES remain poorly understood.Patient concerns:Here we reported two Chinese children presenting clinical manifestations of HIES.Diagnosis:Based on medical history, clinical manifestations, and laboratory findings, a diagnosis of HIES was made for both children. Targeted next-generation sequencing (NGS) identified a novel heterozygous deletion of 15 bp (c.1960_1974del, p.G654_D658del or alternatively c.1966_1980del, and p.G656_D660del), and a recurrent missense mutation (c.1144C>T, p.R382W) in STAT3 in the two patients, respectively.Interventions:The two patients have been given the successful treatment of skin infections with cefaclor.Outcomes:Both patients have been under follow-up for more than 6 months, with no signs of recurrent infections.Lessons:Our results extend the spectrum of STAT3 mutations associated with ADHIES and highlight the value of targeted NGS in confirming diagnosis of genetic disorders.

Hyper-IgE syndrome

Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency condition. It is characterized by the triad of recurrent skin and lung infections, chronic dermatitis, and elevated serum Ig E level. An 8-year-old girl presented with recurrent papulovesicular lesions on the neck, axillae, cubital, and popliteal fossae since 3 years of age. The lesions healed with scarring. There was a history of recurrent diarrhea. Cutaneous examination revealed flexural dermatitis consisting of crusted lesions on the ears, neck, axillae, groins, and genitalia. The ears were deformed, and there was atrophic scarring on the face and eyelids. Routine blood investigations revealed hypereosinophilia. Serum IgE level was >2000 KIU/L. A diagnosis of HIES was made and treated with a short course of oral antibiotics, topical steroid-antibiotic combination. Children affected with HIES can develop life-threatening pulmonary infections. Hence, early diagnosis and proper management are necessary.

Hyper-IgE syndrome in adulthood: a case report and literature review

Objective: To describe the clinical features of hyper-IgE syndrome (HIES), with emphasis on refractory pulmonary cystic lesions as the initial presentation in adulthood. Methods: A case of HIES presenting with pulmonary cystic lesions in an adult patient was retrospectively analyzed. We used "hyper-IgE syndrome" as the Chinese keywords, "hyper-IgE syndrome, China" as the English keywords to retrieve the literature from Wanfang database/CNKI database and Pubmed database until April 2016. The clinical data were pooled and analyzed. Results: A 19 year old female patient was admitted to our hospital because of recurrent cough and expectoration as the chief complaint. Physical examination revealed broad nasal bridge and scoliosis, and chest CT showed gradually enlarged and increased cystic lesions. Laboratory studies demonstrated significantly increased blood eosinophils and serum level of total IgE, together with a definite chemotactic dysfunction of neutrophils. A further detection of STAT3 mutation was negative. The diagnosis of HIES was made and antibiotic treatment resulted in disease remission. Literature review found 45 reports including 37 in Chinese and 11 in English. Eight cases of adult HIES were reported, and all the patients were male, aging 18 to 31 years. Prolonged disease course, recurrent infection and formation of cystic lesions in the lungs were important features of HIES. Early diagnosis and treatment with specific antibiotics were important for improving outcome of the patients. Conclusion: Refractory pulmonary cystic lesions can be the initial presentation in adult HIES. Understanding of the clinical characteristics of HIES will be helpful to avoid misdiagnosis and improve prognosis.

The extended clinical phenotype of 64 patients with dedicator of cytokinesis 8 deficiency

Mutations in dedicator of cytokinesis 8 (DOCK8) cause a combined immunodeficiency (CID) also classified as autosomal recessive (AR) hyper-IgE syndrome (HIES). Recognizing patients with CID/HIES is of clinical importance because of the difference in prognosis and management. We sought to define the clinical features that distinguish DOCK8 deficiency from other forms of HIES and CIDs, study the mutational spectrum of DOCK8 deficiency, and report on the frequency of specific clinical findings. Eighty-two patients from 60 families with CID and the phenotype of AR-HIES with (64 patients) and without (18 patients) DOCK8 mutations were studied. Support vector machines were used to compare clinical data from 35 patients with DOCK8 deficiency with those from 10 patients with AR-HIES without a DOCK8 mutation and 64 patients with signal transducer and activator of transcription 3 (STAT3) mutations. DOCK8-deficient patients had median IgE levels of 5201 IU, high eosinophil levels of usually at least 800/μL (92% of patients), and low IgM levels (62%). About 20% of patients were lymphopenic, mainly because of low CD4(+) and CD8(+) T-cell counts. Fewer than half of the patients tested produced normal specific antibody responses to recall antigens. Bacterial (84%), viral (78%), and fungal (70%) infections were frequently observed. Skin abscesses (60%) and allergies (73%) were common clinical problems. In contrast to STAT3 deficiency, there were few pneumatoceles, bone fractures, and teething problems. Mortality was high (34%). Acombination of 5 clinical features was helpful in distinguishing patients with DOCK8 mutations from those with STAT3 mutations. DOCK8 deficiency is likely in patients with severe viral infections, allergies, and/or low IgM levels who have a diagnosis of HIES plus hypereosinophilia and upper respiratory tract infections in the absence of parenchymal lung abnormalities, retained primary teeth, and minimal trauma fractures.

Food allergy in patients with primary immunodeficiency diseases: Prevalence within the US Immunodeficiency Network (USIDNET)

Food allergy in patients with primary immunodeficiency diseases: Prevalence within the US Immunodeficiency Network (USIDNET)

Artritis séptica en un caso de síndrome de hiperinmunoglobulinemia E

Hyper-IgE syndrome (HIES) is characterized by recurrent skin and pulmonary infections (mainly bacterial), eczematous dermatitis and elevated serum IgE levels. Associated abnormalities in some patients include coarse facial features, failure or delay of shedding of primary teeth, recurrent fractures, hyperextensible joints, and scoliosis. Laboratory abnormalities include elevated total serum IgE levels, typically ranging from 1000 to greater than 50,000 IU/mL and variable eosinophilia. The diagnosis of HIES is based upon the presence of suggestive clinical and laboratory findings. A definitive laboratory test is not commercially available at present. Management of patients with HIES is focused on skin care, prevention of infection, prompt and complete treatment of infections that do develop, and control of pulmonary complications.

Hyper-IgE syndrome, or not

Rationale The underlying immunodeficiency of the hyper-IgE syndrome is unclear and patients characterized as having this disorder may have a different immunodeficiency disease altogether. We present a patient with many of the classic clinical characteristics of hyper-IgE syndrome but an immunologic profile that differs from previously reported cases. Methods The patient is a 34 year old male diagnosed with hyper-IgE syndrome as a child based on his clinical presentation of recurrent Staphylococcus aureus soft tissue and pulmonary infections with resultant pneumatocele formation, eczematoid dermatitis, characteristic facial features, and elevated IgE level (10,000 IU/mL). Radiologic studies and laboratory immunologic profile were obtained on referral as an adult. Results White blood cell count and differential were normal but flow cytometry revealed a moderate B lymphopenia. Mitogen studies showed a normal proliferation response. Candida skin test was positive. Serum immunoglobulin levels were normal except for an elevated IgE of 1461, and anti-pneumococcal and anti-tetanus toxoid antibody titers were at a normal (protective) post-vaccination concentration. Immune response to the neoantigen bacteriophage phi X174 showed an adequate primary antibody response in the first week followed by a sharp decrease in the following three weeks; secondary antibody response was also poor with a relatively low percentage of IgG. Chest CT revealed cystic bronchiectasis. Conclusions This patients immunologic profile and finding of bronchiectasis are distinctly uncharacteristic of hyper-IgE syndrome. The diagnosis of hyper IgE syndrome may be better made after adequate response to Bacteriophage challenge.

Cutaneous manifestations of hyper-IgE syndrome in infants and children

We describe 8 children with hyper-IgE syndrome who had papulopustular eruption on the face and scalp in the first year of life. Seven of the 8 patients had persistent peripheral eosinophilia and 3 had leukocytosis noted before diagnosis. Skin biopsy specimens in 6 patients revealed spongiosis and perivascular dermatitis and/or folliculitis with a predominance of eosinophils. Two patients had bone fractures and osteopenia. Recurrent pneumonia occurred in 6 children and pneumatoceles in 5. The diagnosis of hyper-IgE syndrome was made an average of 18 months after the onset of the initial papulopustular eruption. These findings may lead to earlier recognition of the disease and institution of appropriate treatment. (J Pediatr 2002;141:572-5)